Connecting: the use of information and communication technologies by older adults in a retirement community

This is a long-term study of the use of information and communication technologies by 30 older adults (ages 70–97) living in a large retirement community. The study spanned the years of 1996 to 2008, during which time the research participants grappled with the challenges of computer use while aging 12 years. The researcher, herself a ‘mature learner,’ used a qualitative research design which included observations and open-ended interviews. Using a strategy of “intermittent immersion,” she spent an average of two weeks per visit on site and participated in the lives of the research population in numerous ways, including service as their computer tutor. With e-mail and telephone contact, she was able to continue her interactions with participants throughout the 12-year period. A long-term perspective afforded the view of the evolution, devolution or cessation of the technology use by these older adults, and this process is chronicled in detail through five individual “profiles.” Three research questions dominated the inquiry: What function do computers serve in the lives of older adults? Does computer use foster or interfere with social ties? Is social support necessary for success in the face of challenging learning tasks? In answer to the first question, it became clear that computers were valued as a symbol of competence and intelligence. Some individuals brought their computers with them when transferred to the single-room residences of assisted living or nursing care facilities. Even when use had ceased, their computers were displayed to signal that their owners were or had once been keeping up to date. In answer to the second question, computer owners socialized around computing use (with in-person family members or friends) more than, or as much as, they socialized through their computers in the digital realm of the Internet. And in answer to the third question, while the existence of social support did facilitate computer exploration, more important was the social support network generated and developed among fellow computer users.

Variability in the growth, feeding and condition of barramundi (Lates calcarifer Bloch) in a northern Australian coastal river and impoundment

Lates calcarifer supports important fisheries throughout tropical Australia. Community-driven fish stocking has resulted in the creation of impoundment fisheries and supplemental stocking of selected wild riverine populations. Using predominantly tag-recapture methods, condition assessment and stomach flushing techniques, this study compared the growth of stocked and wild L. calcarifer in a tropical Australian river (Johnstone River) and stocked fish in a nearby impoundment (Lake Tinaroo). Growth of L. calcarifer in the Johnstone River appeared resource-limited, with juvenile fish in its lower freshwater reaches feeding mainly on small aytid shrimp and limited quantities of fish. Growth was probably greatest in estuarine and coastal areas than in the lower freshwater river. Fish in Lake Tinaroo, where prey availability was greater, grew faster than either wild or stocked fish in the lower freshwater areas of the Johnstone River. Growth of L. calcarifer was highly seasonal with marked declines in the cooler months. This was reflected in both stomach fullness and the percentage of fish with empty stomachs but the condition of L. calcarifer was similar across most sites. In areas where food resources appear stretched, adverse effects on resident L. calcarifer populations and their attendant prey species should be minimised through cessation of, or more conservative, stocking practices.

Applying Mathematical Models to Study the Role of the Immune System in Chronic Myelogenous Leukemia

Although tyrosine kinase inhibitors (TKIs) such as imatinib have transformed chronic myelogenous leukemia (CML) into a chronic condition, these therapies are not curative in the majority of cases. Most patients must continue TKI therapy indefinitely, a requirement that is both expensive and that compromises a patient's quality of life. While TKIs are known to reduce leukemic cells' proliferative capacity and to induce apoptosis, their effects on leukemic stem cells, the immune system, and the microenvironment are not fully understood. A more complete understanding of their global therapeutic effects would help us to identify any limitations of TKI monotherapy and to address these issues through novel combination therapies. Mathematical models are a complementary tool to experimental and clinical data that can provide valuable insights into the underlying mechanisms of TKI therapy. Previous modeling efforts have focused on CML patients who show biphasic and triphasic exponential declines in BCR-ABL ratio during therapy. However, our patient data indicates that many patients treated with TKIs show fluctuations in BCR-ABL ratio yet are able to achieve durable remissions. To investigate these fluctuations, we construct a mathematical model that integrates CML with a patient's autologous immune response to the disease. In our model, we define an immune window, which is an intermediate range of leukemic concentrations that lead to an effective immune response against CML. While small leukemic concentrations provide insufficient stimulus, large leukemic concentrations actively suppress a patient's immune system, thus limiting it's ability to respond. Our patient data and modeling results suggest that at diagnosis, a patient's high leukemic concentration is able to suppress their immune system. TKI therapy drives the leukemic population into the immune window, allowing the patient's immune cells to expand and eventually mount an efficient response against the residual CML. This response drives the leukemic population below the immune window, causing the immune population to contract and allowing the leukemia to partially recover. The leukemia eventually reenters the immune window, thus stimulating a sequence of weaker immune responses as the two populations approach equilibrium. We hypothesize that a patient's autologous immune response to CML may explain the fluctuations in BCR-ABL ratio that are regularly seen during TKI therapy. These fluctuations may serve as a signature of a patient's individual immune response to CML. By applying our modeling framework to patient data, we are able to construct an immune profile that can then be used to propose patient-specific combination therapies aimed at further reducing a patient's leukemic burden. Our characterization of a patient's anti-leukemia immune response may be especially valuable in the study of drug resistance, treatment cessation, and combination therapy.

Identifying health inequalities in individuals with major mental illness (MMI) using routine data

Abstract and Summary of Thesis: Background: Individuals with Major Mental Illness (such as schizophrenia and bipolar disorder) experience increased rates of physical health comorbidity compared to the general population. They also experience inequalities in access to certain aspects of healthcare. This ultimately leads to premature mortality. Studies detailing patterns of physical health comorbidity are limited by their definitions of comorbidity, single disease approach to comorbidity and by the study of heterogeneous groups. To date the investigation of possible sources of healthcare inequalities experienced by individuals with Major Mental Illness (MMI) is relatively limited. Moreover studies detailing the extent of premature mortality experienced by individuals with MMI vary both in terms of the measure of premature mortality reported and age of the cohort investigated, limiting their generalisability to the wider population. Therefore local and national data can be used to describe patterns of physical health comorbidity, investigate possible reasons for health inequalities and describe mortality rates. These findings will extend existing work in this area. Aims and Objectives: To review the relevant literature regarding: patterns of physical health comorbidity, evidence for inequalities in physical healthcare and evidence for premature mortality for individuals with MMI. To examine the rates of physical health comorbidity in a large primary care database and to assess for evidence for inequalities in access to healthcare using both routine primary care prescribing data and incentivised national Quality and Outcome Framework (QOF) data. Finally to examine the rates of premature mortality in a local context with a particular focus on cause of death across the lifespan and effect of International Classification of Disease Version 10 (ICD 10) diagnosis and socioeconomic status on rates and cause of death. Methods: A narrative review of the literature surrounding patterns of physical health comorbidity, the evidence for inequalities in physical healthcare and premature mortality in MMI was undertaken. Rates of physical health comorbidity and multimorbidity in schizophrenia and bipolar disorder were examined using a large primary care dataset (Scottish Programme for Improving Clinical Effectiveness in Primary Care (SPICE)). Possible inequalities in access to healthcare were investigated by comparing patterns of prescribing in individuals with MMI and comorbid physical health conditions with prescribing rates in individuals with physical health conditions without MMI using SPICE data. Potential inequalities in access to health promotion advice (in the form of smoking cessation) and prescribing of Nicotine Replacement Therapy (NRT) were also investigated using SPICE data. Possible inequalities in access to incentivised primary healthcare were investigated using National Quality and Outcome Framework (QOF) data. Finally a pre-existing case register (Glasgow Psychosis Clinical Information System (PsyCIS)) was linked to Scottish Mortality data (available from the Scottish Government Website) to investigate rates and primary cause of death in individuals with MMI. Rate and primary cause of death were compared to the local population and impact of age, socioeconomic status and ICD 10 diagnosis (schizophrenia vs. bipolar disorder) were investigated. Results: Analysis of the SPICE data found that sixteen out of the thirty two common physical comorbidities assessed, occurred significantly more frequently in individuals with schizophrenia. In individuals with bipolar disorder fourteen occurred more frequently. The most prevalent chronic physical health conditions in individuals with schizophrenia and bipolar disorder were: viral hepatitis (Odds Ratios (OR) 3.99 95% Confidence Interval (CI) 2.82-5.64 and OR 5.90 95% CI 3.16-11.03 respectively), constipation (OR 3.24 95% CI 3.01-3.49 and OR 2.84 95% CI 2.47-3.26 respectively) and Parkinson’s disease (OR 3.07 95% CI 2.43-3.89 and OR 2.52 95% CI 1.60-3.97 respectively). Both groups had significantly increased rates of multimorbidity compared to controls: in the schizophrenia group OR for two comorbidities was 1.37 95% CI 1.29-1.45 and in the bipolar disorder group OR was 1.34 95% CI 1.20-1.49. In the studies investigating inequalities in access to healthcare there was evidence of: under-recording of cardiovascular-related conditions for example in individuals with schizophrenia: OR for Atrial Fibrillation (AF) was 0.62 95% CI 0.52 - 0.73, for hypertension 0.71 95% CI 0.67 - 0.76, for Coronary Heart Disease (CHD) 0.76 95% CI 0.69 - 0.83 and for peripheral vascular disease (PVD) 0.83 95% CI 0.72 - 0.97. Similarly in individuals with bipolar disorder OR for AF was 0.56 95% CI 0.41-0.78, for hypertension 0.69 95% CI 0.62 - 0.77 and for CHD 0.77 95% CI 0.66 - 0.91. There was also evidence of less intensive prescribing for individuals with schizophrenia and bipolar disorder who had comorbid hypertension and CHD compared to individuals with hypertension and CHD who did not have schizophrenia or bipolar disorder. Rate of prescribing of statins for individuals with schizophrenia and CHD occurred significantly less frequently than in individuals with CHD without MMI (OR 0.67 95% CI 0.56-0.80). Rates of prescribing of 2 or more anti-hypertensives were lower in individuals with CHD and schizophrenia and CHD and bipolar disorder compared to individuals with CHD without MMI (OR 0.66 95% CI 0.56-0.78 and OR 0.55 95% CI 0.46-0.67, respectively). Smoking was more common in individuals with MMI compared to individuals without MMI (OR 2.53 95% CI 2.44-2.63) and was particularly increased in men (OR 2.83 95% CI 2.68-2.98). Rates of ex-smoking and non-smoking were lower in individuals with MMI (OR 0.79 95% CI 0.75-0.83 and OR 0.50 95% CI 0.48-0.52 respectively). However recorded rates of smoking cessation advice in smokers with MMI were significantly lower than the recorded rates of smoking cessation advice in smokers with diabetes (88.7% vs. 98.0%, p<0.001), smokers with CHD (88.9% vs. 98.7%, p<0.001) and smokers with hypertension (88.3% vs. 98.5%, p<0.001) without MMI. The odds ratio of NRT prescription was also significantly lower in smokers with MMI without diabetes compared to smokers with diabetes without MMI (OR 0.75 95% CI 0.69-0.81). Similar findings were found for smokers with MMI without CHD compared to smokers with CHD without MMI (OR 0.34 95% CI 0.31-0.38) and smokers with MMI without hypertension compared to smokers with hypertension without MMI (OR 0.71 95% CI 0.66-0.76). At a national level, payment and population achievement rates for the recording of body mass index (BMI) in MMI was significantly lower than the payment and population achievement rates for BMI recording in diabetes throughout the whole of the UK combined: payment rate 92.7% (Inter Quartile Range (IQR) 89.3-95.8 vs. 95.5% IQR 93.3-97.2, p<0.001 and population achievement rate 84.0% IQR 76.3-90.0 vs. 92.5% IQR 89.7-94.9, p<0.001 and for each country individually: for example in Scotland payment rate was 94.0% IQR 91.4-97.2 vs. 96.3% IQR 94.3-97.8, p<0.001. Exception rate was significantly higher for the recording of BMI in MMI than the exception rate for BMI recording in diabetes for the UK combined: 7.4% IQR 3.3-15.9 vs. 2.3% IQR 0.9-4.7, p<0.001 and for each country individually. For example in Scotland exception rate in MMI was 11.8% IQR 5.4-19.3 compared to 3.5% IQR 1.9-6.1 in diabetes. Similar findings were found for Blood Pressure (BP) recording: across the whole of the UK payment and population achievement rates for BP recording in MMI were also significantly reduced compared to payment and population achievement rates for the recording of BP in chronic kidney disease (CKD): payment rate: 94.1% IQR 90.9-97.1 vs.97.8% IQR 96.3-98.9 and p<0.001 and population achievement rate 87.0% IQR 81.3-91.7 vs. 97.1% IQR 95.5-98.4, p<0.001. Exception rates again were significantly higher for the recording of BP in MMI compared to CKD (6.4% IQR 3.0-13.1 vs. 0.3% IQR 0.0-1.0, p<0.001). There was also evidence of differences in rates of recording of BMI and BP in MMI across the UK. BMI and BP recording in MMI were significantly lower in Scotland compared to England (BMI:-1.5% 99% CI -2.7 to -0.3%, p<0.001 and BP: -1.8% 99% CI -2.7 to -0.9%, p<0.001). While rates of BMI and BP recording in diabetes and CKD were similar in Scotland compared to England (BMI: -0.5 99% CI -1.0 to 0.05, p=0.004 and BP: 0.02 99% CI -0.2 to 0.3, p=0.797). Data from the PsyCIS cohort showed an increase in Standardised Mortality Ratios (SMR) across the lifespan for individuals with MMI compared to the local Glasgow and wider Scottish populations (Glasgow SMR 1.8 95% CI 1.6-2.0 and Scotland SMR 2.7 95% CI 2.4-3.1). Increasing socioeconomic deprivation was associated with an increased overall rate of death in MMI (350.3 deaths/10,000 population/5 years in the least deprived quintile compared to 794.6 deaths/10,000 population/5 years in the most deprived quintile). No significant difference in rate of death for individuals with schizophrenia compared with bipolar disorder was reported (6.3% vs. 4.9%, p=0.086), but primary cause of death varied: with higher rates of suicide in individuals with bipolar disorder (22.4% vs. 11.7%, p=0.04). Discussion: Local and national datasets can be used for epidemiological study to inform local practice and complement existing national and international studies. While the strengths of this thesis include the large data sets used and therefore their likely representativeness to the wider population, some limitations largely associated with using secondary data sources are acknowledged. While this thesis has confirmed evidence of increased physical health comorbidity and multimorbidity in individuals with MMI, it is likely that these findings represent a significant under reporting and likely under recognition of physical health comorbidity in this population. This is likely due to a combination of patient, health professional and healthcare system factors and requires further investigation. Moreover, evidence of inequality in access to healthcare in terms of: physical health promotion (namely smoking cessation advice), recording of physical health indices (BMI and BP), prescribing of medications for the treatment of physical illness and prescribing of NRT has been found at a national level. While significant premature mortality in individuals with MMI within a Scottish setting has been confirmed, more work is required to further detail and investigate the impact of socioeconomic deprivation on cause and rate of death in this population. It is clear that further education and training is required for all healthcare staff to improve the recognition, diagnosis and treatment of physical health problems in this population with the aim of addressing the significant premature mortality that is seen. Conclusions: Future work lies in the challenge of designing strategies to reduce health inequalities and narrow the gap in premature mortality reported in individuals with MMI. Models of care that allow a much more integrated approach to diagnosing, monitoring and treating both the physical and mental health of individuals with MMI, particularly in areas of social and economic deprivation may be helpful. Strategies to engage this “hard to reach” population also need to be developed. While greater integration of psychiatric services with primary care and with specialist medical services is clearly vital the evidence on how best to achieve this is limited. While the National Health Service (NHS) is currently undergoing major reform, attention needs to be paid to designing better ways to improve the current disconnect between primary and secondary care. This should then help to improve physical, psychological and social outcomes for individuals with MMI.

Analyse de survie sur les prédicteurs de la durée d’un processus thérapeutique individuel chez les hommes auteurs de violence conjugale

La violence conjugale est un problème social qui engendre des coûts sérieux (Statistique Canada, 2016). Son traitement est important. Les taux d’abandon thérapeutique observés dans les programmes de traitement en groupe pour les hommes auteurs de comportements violents en contexte conjugal se situent entre 15 et 58 % (Jewell & Wormith, 2010). Ces hauts taux d’abandon réduisent l’efficacité réelle des suivis pour violence conjugale (Bowen & Gilchrist, 2006). Des études montrent que l’âge, l’occupation, le statut conjugal, le faible revenu, l’expérience de violence physique à l’enfance, la consommation de drogue et d’alcool, ainsi que la personnalité colérique et la fréquence des comportements de violence sont des variables qui permettent de prédire l’abandon d’un programme de traitement de la violence conjugale en format de groupe et de type fermé (Jewell & Wormith, 2010). Aucune étude recensée n’a étudié les prédicteurs liés à l’abandon thérapeutique d’un traitement en format individuel de type ouvert. Cette étude visait à identifier quels sont les moments-clés où il y a cessation du suivi pour violence conjugale et à vérifier quelles variables sont associées à une cessation plus ou moins précoce du traitement individuel des hommes auteurs de violence conjugale. Une batterie de questionnaires auto-rapportés a été soumise à 206 hommes francophones qui amorcent une consultation individuelle pour un problème de violence conjugale dans un centre communautaire de la province de Québec. Parmi ceux-ci se trouvaient des questionnaires évaluant l’expérience de la colère, les comportements de violence conjugale, les insécurités d’attachement amoureux et la désirabilité sociable. Le nombre de séances complétées par chaque participant a également été obtenu par le biais de l’organisme. Une première analyse de survie a permis de produire une table de survie et d’identifier trois moments où la cessation du suivi est la plus fréquente, soient une cessation précoce (1 ou 2 séances), une cessation à court terme (3 à 5 séances) et une cessation à moyen terme (après la 11e séance). L’analyse de survie par régression de Cox a ensuite permis de montrer que l’âge, le fait d’avoir complété ou non des études post-secondaires, le fait d’avoir une occupation stable (emploi ou études à temps plein) ou non, le fait de consulter sous ordonnance légale, le niveau de violence psychologique émise, ainsi que les insécurités d’attachement (évitement de l’intimité, anxiété d’abandon) sont tous des prédicteurs significatifs du moment de cessation d’un suivi individuel de type ouvert pour violence conjugale. Plus précisément, les participants qui n’ont pas complété d’études post-secondaires, qui sont sans occupation stable, qui consultent sous ordonnance de la Cour ou de la DPJ et qui présentent peu d’évitement de l’intimité ont davantage tendance à cesser leur suivi de façon précoce; les participants qui ont complété des études post-secondaires et qui présentent peu d’anxiété d’abandon ont davantage tendance à cesser leur suivi à court terme; les clients qui posent moins d’actes de violence psychologique ont davantage tendance à mettre fin à leur suivi à moyen terme. Les implications cliniques de ces résultats sont discutées

Seizure and Profound Hypokalemia: Unusual Presentation of Primary Hyperparathyroidism

A 68-year-old man was admitted because of tonic–clonic convulsion. He had been receiving 200 mg itraconazole for 10 days. He had hypokalaemia (2.2 mEq/l), hypercalcaemia (Cacorr 11.0 mg/dl) and elevated serum parathyroid hormone (PTH, 95 pg/ml). Ultrasound examination of the neck revealed a low echoic tumour. Cessation of itraconazole and fluid supplementation eradicated clinical symptoms and profound hypokalaemia, but serum potassium remained low normal (3.4 mEq/l) and the mild hypercalcaemia and elevated PTH were unchanged. To conclude, a small amount of itraconazole (200 mg) precipitated profound hypokalaemia and seizure in a patient with mild hyperparathyroidism and low normal serum potassium.

Riffe und fazielle Entwicklung der florigemma-Bank (Korallenoolith, Oxfordium) im Süntel und östlichen Wesergebirge (NW-Deutschland

During the Sedimentation of the platform carbonate deposits of the Korallenoolith Formation (middle Oxfordian to early Kimmeridgian) small buildups ofcorals formed in the Lower Saxony Basin. These bioconstructions are restricted to particular horizons (Untere Korallenbank,ßorigenuna-Bank Member etc.) and represent patch reefs and biostromes. In this study, the development of facies, fossil assemblages, spatial distribution of fossils, and reefs of the ßorigenuna-Bank Member (upper Middle Oxfordian) in the Süntel Mts and the eastern Wesergebirge Mts is described; the formation of reefs is discussed in detail. Twelve facies types are described and interpreted. They vary between high-energy deposits as well winnowed oolites and quiet-water lagoonal mudstones. Owing to the significance of biota, micro- and macrofossils are systematically described. The reefs are preserved in growth position, are characterized by numerous corresponding features and belong to a certain reef type. According to their size, shape and framework, they represent patch reefs, coral knobs (sensu James, 1983), coral thrombolite reefs (sensu Leinfelder et al., 1994) or “Klein- and Mitteldickichte” (sensu Laternser, 2001). Their growth fabric corresponds to the superstratal (dense) pillarstone (sensu Insalaco, 1998). As the top of the ßorigenuna-Bank displays an erosional unconformity (so-called Hauptdiskontinuität), the top of the reefs are erosionally capped. Their maximum height amounts to at least the maximum thickness of the ßorigenuna-Bank which does not exceed 4 metres. The diversity of coral fauna of the reefs is relatively low; a total of 13 species is recorded. The coral community is over- whelmingly dominated by the thin-branched ramose Thamnasteria dendroidea (Lamouroux) that forms aggregations of colonies (77?. dendroidea thickets). Leafy to platy Fungiastrea arachnoides (Parkinson) and Thamnasteria concinna (Goldfuss) occur subordinately, other species are only of minor importance. In a few cases, the reef-core consisting of Th. dendroidea thickets is laterally encrusted by platy F. arachnoides and Th. concinna colonies, and microbial carbonates. This zonation reflects probably a succession of different reef builders as a result of changing environmental conditions (allogenic succession). Moreover, some reefs are overlain by a biostrome made of large Solenopora jurassica nodules passing laterally in a nerinean bed. Mikrobial carbonates promoted reef growth and favoured the preservation of reef organismn in their growth position or in situ. They exhibit a platy, dendroid, or reticulate growth form or occur as downward-facing hemispheroids. According to their microstructure, they consist of a peloidal, clotted, or unstructured fabric (predominately layered and poorly structured thrombolite as well as clotted leiolite) (sensu Schmid, 1996). Abundant endo- and epibiontic organisms (bivalves, gastropods, echinoids, asteroids, ophiuroids, crabs etc) are linked to the reefs. With regard to their guild structure, the reefs represent occurrences at which only a few coral species serve as builder. Moreover, microbial carbonates contribute to both building and binding of the reefs. Additional binder as well as baffler are present, but not abundant. According to the species diversity, the dweller guild comprises by far the highest number of invertebrate taxa. The destroyer guild chiefly encompasses bivalves. The composition of the reef community was influenced by the habitat structure of the Th. dendroidea thickets. Owing to the increase in encrusting organisms and other inhabitants of the thickets, the locational factors changed, since light intensity and hydrodynamic energy level and combined parameters as oxygen supply declined in the crowded habitat. Therefore a characteristic succession of organisms is developed that depends on and responds to changing environmental conditions („community replacement sequence“). The succession allows the differentiation of different stages. It started after the cessation of the polyps with boring organisms and photoautotrophic micro-encrusters (calcareous algae, Lithocodium aggregatum). Following the death of these pioneer organisms, encrusting and adherent organisms (serpulids, „Terebella“ species, bryozoans, foraminifers, thecideidinids, sklerospongid and pharetronid sponges, terebratulids), small mobile organisms (limpets), and microbial induced carbonates developed. The final stage in the community replacement sequence gave rise to small cryptic habitats and organisms that belong to these caves (cryptobionts, coelobites). The habitat conditions especially favoured small non-rigid demosponges (“soft sponges”) that tolerate reduced water circulation. Reef rubble is negligible, so that the reefs are bordered by fossiliferous micritic limestone passing laterally in micritic limestone. Approximately 10% of the study area (outcropping florigemma-Bank) corresponds to reefal deposits whereas the remaining 90% encompass lagoonal inter-reefal deposits. The reef development is a good example for the interaction between reef growth, facies development and sea-level changes. It was initiated by a sea-level rise (transgression) and corresponding decrease in the hydrodynamic energy level. Colonization and reef growth took place on a coarse-grained Substrate composed of oncoids, larger foraminifers and bioclasts. Reef growth took place in a calm marine lagoonal setting. Increasing abundance of spherical coral morphs towards the Northeast (section Kessiehausen, northwestem Süntel Mts) reflects higher turbidity and a facies transition to coral occurrences of the ßorigenuna-Bank Member in the adjacent Deister Mts. The reef growth was neither influenced by stonns nor by input of siliciclastic deposits, and took place in short time - probably in only a thousand years under most probably mesotrophic conditions. The mass appearance of solenoporids and nerineids in the upper part of the ßorigenuna-Bank Member point to enhanced nutrient level as a result of regression. In addition, this scenario of fluctuations in nutrient availability seems to be responsible for the cessation of reef corals. The sea level fall reached its climax in the subaerial exposure and palaeokarst development of the florigemma-Bank. The reef building corals are typical pioneer species. The blade-like, flattened F. amchnoides colonies are characterized by their light porous calcium carbonate skeleton, which is a distinct advantage in soft bottom environment. Thus, they settled on soft bottom exposing the large parts of its surface to the incoming light. On the other hand, in response to their light requirements they were also able to settle shaded canopy structures or reef caves. Th. dendroidea is an opportunistic coral species in very shallow, well illuminated marine environment. Their thin and densely spaced branches led to a very high surface/volume ratio of the colonies that were capable to exploit incoming light due to their small thamasterioid calices characterized by “highly integrated polyps”. In addition, sideward coalescence of branches during colony growth led to a wave-resistant framework and favoured the authochthonous preservation of the reefs. Asexual reproduction by fragmented colonies promoted reef development as Th. dendroidea thickets laterally extend over the sea floor or new reefs have developed from broken fragments of parent colonies. Similar build ups with Th. dendroidea as a dominant or frequent reef building coral species are known from the Paris Basin and elsewhere from the Lower Saxony Basin (Kleiner Deister Mts). These buildups developed in well-illuminated shallow water and encompass coral reefs or coral thrombolite reefs. Intra- and inter-reef deposits vary between well-winnowed reef debris limestone and mudstones representing considerably calmer conditions. Solenoporid, nerineids and diceratides belong to the characteristic fossils of these occurrences. However, diceratides are missing in theflorigemma-Bank Member. Th. dendroidea differs in its colonization of low- to high-energy environment from recent ramose scleractinian corals (e.g., Acropora and Porites sp.). The latter are restricted to agitated water habitats creating coral thickets and carpets. According to the morphologic plasticity of Th. dendroidea, thick-branched colonies developed in a milieu of high water energy, whereas fragile, wide- and thin-branched colonies prevail in low-energy settings. Due to its relatively rapid growth, Th. dendroidea was able to keep pace with increased Sedimentation rates. 68 benthonic foraminiferan species/taxa have been recognized in thin sections. Agglutinated foraminifers (textulariids) predominate when compared with rotaliids and milioliids. Numerous species are restricted to a certain facies type or occur in higher population densities, in particular Everticyclammina sp., a larger agglutinated foraminifer that occurs in rock building amounts. Among the 25 reef dwelling foraminiferal species, a few were so far only known from Late Jurassic sponge reefs. Another striking feature is the frequency of adherent foraminiferal species. Fauna and flora, in particular dasycladaleans and agglutinated foraminifers, document palaeobiogeographic relationships to the Tethys and point to (sub)tropical conditions. Moreover, in Germany this foraminiferan assemblage is yet uncompared. In Southern Germany similar tethyan type assemblages are not present in strata as young as Middle Tithonian.

When you’re ready to quit, we’re here to help

This sheet gives the phone number 1-800-QUIT-NOW (1-800-784-8669) for people to get help to stop smoking.

Accumulation, persistence and effects of indospicine residues in camels fed Indigofera plant

Indospicine (L-2-amino-6-amidinohexanoic acid) is a natural hepatotoxin found in all parts of some Indigofera plants such as I. linnaei and I. spicata. Several studies have documented a susceptibility to this hepatotoxin in different species of animals, including cattle, sheep, dogs and rats, which are associated with mild to severe liver disease after prolonged ingestion. However, there is little published data on the effects of this hepatotoxin in camels, even though Indigofera plants are known to be palatable to camels in central Australia. The secondary poisoning of dogs after prolonged dietary exposure to residual indospicine in camel muscle has raised additional food safety concerns. In this study, a feeding experiment was conducted to investigate the in vivo accumulation, excretion, distribution and histopathological effects of dietary indospicine on camels. Six young camels (2 – 4 year old), weighing 270 − 390 kg were fed daily a roughage diet consisting of Rhodes grass hay and lucerne chaff, supplemented with Indigofera and steam flaked barley. Indigofera (I. spicata) was offered at 597 mg DM/kg body weight (bw)/day designed to deliver 337 µg indospicine/kg bw/day, and fed for a period of 32 days. Blood and muscle biopsies were collected over the period of the study. Concentrations of indospicine in the plasma and muscle biopsy samples were quantitated by validated ultra-performance liquid chromatography−tandem mass spectrometry (UPLC−MS/MS). The highest concentrations in plasma (1.01 mg/L) and muscle (2.63 mg/kg fresh weight (fw)) were found at necropsy (day 33). Other tissues were also collected at necropsy and analysis showed ubiquitous distribution of indospicine, with the highest indospicine accumulation detected in the pancreas (4.86 ± 0.56 mg/kg fw) and liver (3.60 ± 1.34 mg/kg fw); followed by the muscle, heart and kidney. Histopathological examination of liver tissue showed multiple small foci of predominantly mononuclear inflammatory cells. After cessation of Indigofera intake, indospicine present in plasma in the remaining 3 camels had a longer terminal elimination half-life (18.6 days) than muscle (15.9 days), and both demonstrated mono-exponential decreases.

South Carolina COPD Strategic Plan

Chronic obstructive pulmonary disease is the third leading cause of death in South Carolina and affects approximately 15 percent of the adult population. Although tobacco cessation and avoidance are slowly advancing in South Carolina, 20 percent of COPD occurs in non-smokers, and this percentage will likely increase in the coming years. Therefore, a strategic plan must include other initiatives in addition to smoking cessation. This document was developed by a multidisciplinary group of health care providers, public health practitioners, and patients, as such a combined approach is imperative to target this disease.

Adventitious rooting of conifers: influence of biological factors

Vegetative propagation of superior conifer trees can be achieved e.g. through rooted cuttings or rooted microshoots, the latter predominantly through in vitro tissue culture. Both techniques are used to achieve rapid multiplication of trees with favorable genetic combinations and to capture a large proportion of the genetic diversity in a single generation cycle. However, adventitious rooting of shoots (cuttings) is often not efficient due to various problems such as scarcity of roots and cessation of their growth, both of which limit the application of vegetative propagation in some conifer species. Many factors are involved in the adventitious rooting of shoots including physical and chemical ones such as plant growth regulators, carbohydrates, light quality, temperature and rooting substrates or media (reviewed by Ragonezi et al. 2010). The focus of this review is on biological factors, such as inoculations with Agrobacterium rhizogenes, plant- growth-promoting rhizobacteria and other endophytes, and mycorrhizal fungi, which were found to stimulate adventitious rooting. These microorganisms could contribute not only to adventitious root development but also help in protecting conifer plants against pathogenic microorganisms, facilitate acclimation and transplanting, and contribute to more sustainable, chemical-free forests.

Dificuldades no aleitamento materno

Enquadramento: Apesar de o leite materno ser globalmente aceite como o alimento mais completo e efetivo para assegurar a saúde do bebé, além dos claros benefícios para a mãe, continua-se a verificar que a taxa de amamentação está ainda longe da pretendida. Objetivos: Identificar a evidência científica dos determinantes da interrupção do aleitamento materno aos 6 meses de vida do bebé. Métodos: Foi realizada uma revisão sistemática da literatura sobre as dificuldades que levam à interrupção do aleitamento materno aos 6 meses de vida do bebé. Efetuou-se uma pesquisa na PUBMED, The Cochrane Library, Scielo e Google Académic de estudos publicados entre janeiro de 2010 a outubro de 2015, partindo dos critérios de inclusão previamente definidos, os estudos selecionados foram posteriormente avaliados. Dois revisores avaliaram a qualidade dos estudos a incluir, utilizando a grelha para a avaliação crítica de um estudo. Após a avaliação crítica da qualidade, foram incluídos no corpus de estudo 4 artigos com scores entre 87.5% e 95.0%. Resultados: Como metasíntese e seleção da análise dos artigos, inferiu-se que os fatores que levam à interrupção do aleitamento materno aos 6 meses de vida do bebé são: as preocupações com a lactação, perda de peso do bebé, doença da mãe ou a necessidade de tomar medicação, bloqueio dos ductos mamários, problemas relacionados com a gestão psicossocial, conflitos no seu estilo de vida, o posicionamento e pega inadequados, queixa de leite insuficiente ou fraco, dor à amamentação, fissuras, ingurgitamento mamário, a ansiedade materna e o choro da criança. Conclusões: Perante a evidência científica, as causas de abandono do aleitamento materno são multifatoriais e estão associadas à mãe, ao bebé e à saúde. A promoção do aleitamento materno exige programas de educação baseados na evidência, contribuindo para melhoria dos índices nacionais de prevalência da amamentação até, pelo menos aos 6 meses de vida do bebé, que se deseja cada vez mais consentânea com as melhores práticas internacionais. Palavras-Chave: Aleitamento materno; Dificuldades; Interrupção.

Nichtmedikamentöse Sekundärprävention der koronaren Herzkrankheit (KHK)

Hintergrund: Die koronare Herzkrankheit (KHK) ist eine häufige und potenziell tödliche Erkrankung mit einer Lebenszeitprävalenz von über 20%. Allein in Deutschland wird die Zahl der durch die ischämische Herzerkrankung und des akuten Myokardinfarkts jährlich verursachten Todesfälle auf etwa 140.000 geschätzt. Ein Zusammenhang eng mit dem Lebensstil verbundener Risikofaktoren mit Auftreten und Prognose der KHK ist nachgewiesen. Durch Maßnahmen der nichtmedikamentösen Sekundärprävention wird versucht, diese Risikofaktoren positiv zu verändern sowie die KHK im Gegensatz zu palliativen interventionellen Therapiestrategien kausal zu behandeln. Zur Wirksamkeit der nichtmedikamentösen sekundärpräventiven Maßnahmen liegt eine ganze Reihe von Einzelstudien und -untersuchungen vor, eine systematische Analyse, die die Evidenz aller hauptsächlich angewandten Sekundärpräventionsstrategien zusammenfasst, fehlt unseres Wissens nach bislang jedoch. Auch eine Auswertung vorhandener Studien zur Kosten-Effektivität der Maßnahmen ist hierbei zu integieren. Fragestellung: Ziel dieses HTA-Berichts (HTA=Health Technology Assessment) ist die Erstellung einer umfassenden Übersicht der aktuellen Literatur zu nichtmedikamentösen Sekundärpräventionsmaßnahmen in der Behandlung der KHK, um diese Maßnahmen und deren Komponenten bezüglich ihrer medizinischen Wirksamkeit sowie Wirtschaftlichkeit zu beurteilen. Weiterhin sollen die ethischen, sozialen und rechtlichen Aspekte der nichtmedikamentösen Sekundärprävention und die Übertragbarkeit der Ergebnisse auf den deutschen Versorgungsalltag untersucht werden. Methodik: Relevante Publikationen werden über eine strukturierte und hochsensitive Datenbankrecherche sowie mittels Handrecherche identifiziert. Die Literaturrecherche wird in vier Einzelsuchen zu medizinischen, gesundheitsökonomischen, ethischen und juristischen Themen am 18.09.2008 durchgeführt und erstreckt sich über die vergangenen fünf Jahre. Die methodische Qualität der Publikationen wird von jeweils zwei unabhängigen Gutachtern unter Beachtung von Kriterien der evidenzbasierten Medizin (EbM) systematisch geprüft. Ergebnisse: Von insgesamt 9.074 Treffern erfüllen 43 medizinische Publikationen die Selektionskriterien, mit einem Nachbeobachtungszeitraum zwischen zwölf und 120 Monaten. Insgesamt ist die Studienqualität zufriedenstellend, allerdings berichtet nur ca. die Hälfte der Studien differenziert die Gesamtmortalität, während die übrigen Studien andere Outcomemaße verwenden. Die Wirksamkeit einzelner Sekundärpräventionsmaßnahmen stellt sich als sehr heterogen dar. Insgesamt kann langfristig eine Reduktion der kardialen sowie der Gesamtmortalität und der Häufigkeit kardialer Ereignisse sowie eine Erhöhung der Lebensqualität beobachtet werden. Vor allem für trainingsbasierte und multimodale Interventionen ist eine effektive Reduktion der Mortalität zu beobachten, während psychosoziale Interventionen besonders in Bezug auf eine Erhöhung der Lebensqualität effektiv zu sein scheinen. Für die ökonomischen Auswertungen werden 26 Publikationen identifiziert, die von ihrer Themenstellung und Studienart dem hier betrachteten Kontext zugeordnet werden können. Insgesamt kann festgestellt werden, dass sich die Studienlage zur multimodalen Rehabilitation sowohl bezüglich ihrer Menge als auch Qualität der Analysen besser darstellt, als dies für Evaluationen von Einzelmaßnahmen beobachtet werden kann. Die internationale Literatur bestätigt den multimodalen Ansätzen dabei zwar ein gutes Verhältnis von Kosten und Effektivität, untersucht jedoch nahezu ausschließlich ambulante oder häuslichbasierte Maßnahmen. Die Auswertung der Studien, die einzelne sich mit präventiven Maßnahmen in Hinblick auf ihre Kosten-Effektivität beschäftigen, ergibt lediglich positive Tendenzen für Interventionen der Raucherentwöhnung und des körperlichen Trainings. Im Hinblick auf psychosoziale Maßnahmen sowie auch die Ernährungsumstellung können aufgrund der unzureichenden Studienlage jedoch keine Aussagen über die Kosten-Effektivität getroffen werden. Insgesamt werden im Rahmen der Betrachtung sozialer Aspekte der nichtmedikamentösen Sekundärprävention elf Publikationen einbezogen. Die relativ neuen Studien bestätigen, dass Patienten mit niedrigem sozioökonomischen Status insgesamt schlechtere Ausgangsbedingungen und demnach einen spezifischen Bedarf an rehabilitativer Unterstützung haben. Gleichzeitig sind sich die Forscher jedoch uneinig, ob gerade diese Patientengruppe relativ häufiger oder seltener an den Rehabilitationsmaßnahmen teilnimmt. Bezüglich der Barrieren, die Patienten von der Teilnahme an den präventiven Maßnahmen abhalten, werden psychologische Faktoren, physische Einschränkungen aber auch gesellschaftliche und systemisch-orientierte Einflüsse genannt. Diskussion: Nichtmedikamentöse Sekundärpräventionsmaßnahmen sind sicher und in der Lage eine Reduktion der Mortalität sowie der Häufigkeit kardialer Ereignisse zu erzielen sowie die Lebensqualität zu erhöhen. Da nur wenige der methodisch verlässlichen Studien Teilnehmer über einen längeren Zeitraum von mindestens 60 Monaten nachverfolgen, müssen Aussagen über die Nachhaltigkeit als limitiert angesehen werden. Verlässliche Angaben in Bezug auf relevante Patientensubgruppen lassen sich nur sehr eingeschränkt machen ebenso wie im Hinblick auf die vergleichende Beurteilung verschiedener Maßnahmen der Sekundärprävention, da diese von eingeschlossenen Studien nur unzureichend erforscht wurden. Zukünftige methodisch verlässliche Studien sind notwendig, um diese Fragestellungen zu untersuchen und zu beantworten. Bezogen auf die Kosten-Effektivität nichtmedikamentöser sekundärpräventiver Maßnahmen kann aus den internationalen Studien eine insgesamt positive Aussage zusammengefasst werden. Einschränkungen dieser resultieren jedoch zum einen aus den Besonderheiten des deutschen Systems der stationären Rehabilitationsangebote, zum anderen aus den qualitativ mangelhaften Evaluationen der Einzelmaßnahmen. Studien mit dem Ziel der Bewertung der Kosten-Effektivität stationärer Rehabilitationsangebote sind ebenso erforderlich wie auch qualitativ hochwertige Untersuchungen einzeln erbrachter Präventionsmaßnahmen. Aus sozialer Perspektive sollte insbesondere untersucht werden, welche Patientengruppe aus welchen Gründen von einer Teilnahme an Rehabilitations- bzw. präventiven Maßnahmen absieht und wie diesen Argumenten begegnet werden könnte. Schlussfolgerung: Nichtmedikamentöse sekundärpräventive Maßnahmen sind in der Lage eine Reduktion der Mortalität und der Häufigkeit kardialer Ereignisse zu erzielen sowie die Lebensqualität zu erhöhen. Eine Stärkung des Stellenwerts nichtmedikamentöser Maßnahmen der Sekundärprävention erscheint vor diesem Hintergrund notwendig. Auch kann für einige Interventionen ein angemessenes Verhältnis von Effektivität und Kosten angenommen werden. Es besteht allerdings nach wie vor erheblicher Forschungsbedarf bezüglich der Wirksamkeitsbeurteilung nichtmedikamentöser Maßnahmen der Sekundärprävention in wichtigen Patientensubgruppen und der Effizienz zahlreicher angebotener Programme. Darüber hinaus ist weitere Forschung notwendig, um die Nachhaltigkeit der Maßnahmen und Gründe für die Nichtinanspruchnahme detailliert zu untersuchen. Vor allem gilt es jedoch den Versorgungsalltag in Deutschland, wie er sich für Ärzte, Patienten und weitere Akteure des Gesundheitswesens darstellt, zu untersuchen und den heutigen Stellenwert nichtmedikamentöser Maßnahmen aufzuzeigen.

Improving the use of G-CSF during chemotherapy using physiological mathematical modelling : a quantitative systems pharmacology approach

La diminution des doses administrées ou même la cessation complète d'un traitement chimiothérapeutique est souvent la conséquence de la réduction du nombre de neutrophiles, qui sont les globules blancs les plus fréquents dans le sang. Cette réduction dans le nombre absolu des neutrophiles, aussi connue sous le nom de myélosuppression, est précipitée par les effets létaux non spécifiques des médicaments anti-cancéreux, qui, parallèlement à leur effet thérapeutique, produisent aussi des effets toxiques sur les cellules saines. Dans le but d'atténuer cet impact myélosuppresseur, on administre aux patients un facteur de stimulation des colonies de granulocytes recombinant humain (rhG-CSF), une forme exogène du G-CSF, l'hormone responsable de la stimulation de la production des neutrophiles et de leurs libération dans la circulation sanguine. Bien que les bienfaits d'un traitement prophylactique avec le G-CSF pendant la chimiothérapie soient bien établis, les protocoles d'administration demeurent mal définis et sont fréquemment déterminés ad libitum par les cliniciens. Avec l'optique d'améliorer le dosage thérapeutique et rationaliser l'utilisation du rhG-CSF pendant le traitement chimiothérapeutique, nous avons développé un modèle physiologique du processus de granulopoïèse, qui incorpore les connaissances actuelles de pointe relatives à la production des neutrophiles des cellules souches hématopoïétiques dans la moelle osseuse. À ce modèle physiologique, nous avons intégré des modèles pharmacocinétiques/pharmacodynamiques (PK/PD) de deux médicaments: le PM00104 (Zalypsis®), un médicament anti-cancéreux, et le rhG-CSF (filgrastim). En se servant des principes fondamentaux sous-jacents à la physiologie, nous avons estimé les paramètres de manière exhaustive sans devoir recourir à l'ajustement des données, ce qui nous a permis de prédire des données cliniques provenant de 172 patients soumis au protocol CHOP14 (6 cycles de chimiothérapie avec une période de 14 jours où l'administration du rhG-CSF se fait du jour 4 au jour 13 post-chimiothérapie). En utilisant ce modèle physio-PK/PD, nous avons démontré que le nombre d'administrations du rhG-CSF pourrait être réduit de dix (pratique actuelle) à quatre ou même trois administrations, à condition de retarder le début du traitement prophylactique par le rhG-CSF. Dans un souci d'applicabilité clinique de notre approche de modélisation, nous avons investigué l'impact de la variabilité PK présente dans une population de patients, sur les prédictions du modèle, en intégrant des modèles PK de population (Pop-PK) des deux médicaments. En considérant des cohortes de 500 patients in silico pour chacun des cinq scénarios de variabilité plausibles et en utilisant trois marqueurs cliniques, soient le temps au nadir des neutrophiles, la valeur du nadir, ainsi que l'aire sous la courbe concentration-effet, nous avons établi qu'il n'y avait aucune différence significative dans les prédictions du modèle entre le patient-type et la population. Ceci démontre la robustesse de l'approche que nous avons développée et qui s'apparente à une approche de pharmacologie quantitative des systèmes (QSP). Motivés par l'utilisation du rhG-CSF dans le traitement d'autres maladies, comme des pathologies périodiques telles que la neutropénie cyclique, nous avons ensuite soumis l'étude du modèle au contexte des maladies dynamiques. En mettant en évidence la non validité du paradigme de la rétroaction des cytokines pour l'administration exogène des mimétiques du G-CSF, nous avons développé un modèle physiologique PK/PD novateur comprenant les concentrations libres et liées du G-CSF. Ce nouveau modèle PK a aussi nécessité des changements dans le modèle PD puisqu’il nous a permis de retracer les concentrations du G-CSF lié aux neutrophiles. Nous avons démontré que l'hypothèse sous-jacente de l'équilibre entre la concentration libre et liée, selon la loi d'action de masse, n'est plus valide pour le G-CSF aux concentrations endogènes et mènerait en fait à la surestimation de la clairance rénale du médicament. En procédant ainsi, nous avons réussi à reproduire des données cliniques obtenues dans diverses conditions (l'administration exogène du G-CSF, l'administration du PM00104, CHOP14). Nous avons aussi fourni une explication logique des mécanismes responsables de la réponse physiologique aux deux médicaments. Finalement, afin de mettre en exergue l’approche intégrative en pharmacologie adoptée dans cette thèse, nous avons démontré sa valeur inestimable pour la mise en lumière et la reconstruction des systèmes vivants complexes, en faisant le parallèle avec d’autres disciplines scientifiques telles que la paléontologie et la forensique, où une approche semblable a largement fait ses preuves. Nous avons aussi discuté du potentiel de la pharmacologie quantitative des systèmes appliquées au développement du médicament et à la médecine translationnelle, en se servant du modèle physio-PK/PD que nous avons mis au point.

Work stress, smoking status and smoking intensity: an observational study of 46 190 employees

Study objective: To examine the relationship between work stress, as indicated by the job strain model and the effort-reward imbalance model, and smoking. Setting: Ten municipalities and 21 hospitals in Finland. Design and Participants: Binary logistic regression models for the prevalence of smoking were related to survey responses of 37 309 female and 8881 male Finnish public sector employees aged 17-65. Separate multinomial logistic regression models were calculated for smoking intensity for 8130 smokers. In addition, binary logistic regression models for ex-smoking were fitted among 16 277 former and current smokers. In all analyses, adjustments were made for age, basic education, occupational status, type of employment and marital status. Main results: Respondents with high effort-reward imbalance or lower rewards were more likely to be smokers. Among smokers, an increased likelihood of higher intensity of smoking was associated with higher job strain and higher effort-reward imbalance and their components such as low job control and low rewards. Smoking intensity was also higher in active jobs in women, in passive jobs and among employees with low effort expenditure. Among former and current smokers, high job strain, high effort-reward imbalance and high job demands were associated with a higher likelihood of being a current smoker. Lower effort was associated with a higher likelihood of ex-smoking. Conclusions: This evidence suggests an association between work stress and smoking and implies that smoking cessation programs may benefit from the taking into account the modification of stressful features of work environment. Key words: effort-reward imbalance; job strain; smoking. Abbreviations: OR, odds ratio; CI, confidence interval; SES, socioeconomic status