Are the differences in adulthood ill-health across the North-South divide and between Scotland and England also evident in early childhood health indicators?

Regional differences in adult morbidity and mortality within England (i.e., north-south divide or gradient) and between England and Scotland (i.e., Scottish effect) are only partly explained by adult levels of socioeconomic status or risk factors. This suggests variation in early life, and is supported by the fetal origins and life-course literature which posits that birth outcomes and subsequent, cumulative exposures influence adult health. However, no studies have examined the north-south gradient or Scottish effect in health in the earliest years of life. The aims of the study were: i) to examine health indicators in English and Scottish children at birth and age three to establish whether regional differences exist; and ii) to establish whether observed changes in child health at age three were attributable to birth and/or early life environmental exposures. Respondents included 10,639 biological Caucasian mothers of singleton children recruited to the Millennium Cohort Study (MCS) in the year 2000. Outcome variables were: gestational age and birth weight, and height, body mass index (BMI), and externalising behavioural problems at age three. Region/country was categorised as: South (reference), Midlands, North (England), and Scotland. Respondents provided information on child, maternal, household, and socioeconomic characteristics. Results indicated no significant regional variations for gestational age or birth weight. At age three there was a north-south gradient for externalising behaviour and a north-south divide in BMI which attenuated on adjustment. However, a north-south divide in height was not fully explained by adjustment. There was also evidence of a ‘Midlands effect’, with increased likelihood of shorter stature and behaviour problems. Results showed a Scottish effect for height and BMI in the unadjusted models, and height in the adjusted model, but a decreased likelihood of behaviour problems. Findings indicated no regional differences in health at birth, but some regional variation at age three supports the cumulative life-course model.

Current therapeutic strategies to mitigate the eNOS dysfunction in ischaemic stroke

Impairment of endothelial nitric oxide synthase (eNOS) activity is implicated in the pathogenesis of endothelial dysfunction in many diseases including ischaemic stroke. The modulation of eNOS during and/or following ischaemic injury often represents a futile compensatory mechanism due to a significant decrease in nitric oxide (NO) bioavailability coupled with dramatic increases in the levels of reactive oxygen species that further neutralise NO. However, applications of a number of therapeutic agents alone or in combination have been shown to augment eNOS activity under a variety of pathological conditions by potentiating the expression and/or activity of Akt/eNOS/NO pathway components. The list of these therapeutic agents include NO donors, statins, angiotensin-converting enzyme inhibitors, calcium channel blockers, phosphodiesterase-3 inhibitors, aspirin, dipyridamole and ellagic acid. While most of these compounds exhibit anti-platelet properties and are able to up-regulate eNOS expression in endothelial cells and platelets, others suppress eNOS uncoupling and tetrahydrobiopterin (an eNOS stabiliser) oxidation. As the number of therapeutic molecules that modulate the expression and activity of eNOS increases, further detailed research is required to reveal their mode of action in preventing and/or reversing the endothelial dysfunction.

Test methods for concrete durability indicators

Durability of concrete structures is primarily dependent on the environmental influences, i.e. the penetration of aggressive substances in the structural element from the environment. Penetrability is an important durability indicator of concrete and by specifying different classes of penetrability of concrete it should be possible to design a structure with the required resistance to environmental loads. This chapter covers descriptions of the available and commonly applied in situ and laboratory, non-invasive and semi-invasive test methods for evaluating concrete penetrability properties.

All-Cause Mortality up to and After Coronary Heart Disease and Stroke Events in European Middle-Aged Men The PRIME Study

Background and Purpose-The aim was to investigate prospectively the all-cause mortality risk up to and after coronary heart disease (CHD) and stroke events in European middle-aged men.

Methods-The study population comprised 10 424 men 50 to 59 years of age recruited between 1991 and 1994 in France (N=7855) and Northern Ireland (N=2747) within the Prospective Epidemiological Study of Myocardial Infarction. Incident CHD and stroke events and deaths from all causes were prospectively registered during the 10-year follow-up. In Cox's proportional hazards regression analysis, CHD and stroke events during follow-up were used as time-dependent covariates.

Results-A total of 769 CHD and 132 stroke events were adjudicated, and 569 deaths up to and 66 after CHD or stroke occurred during follow-up. After adjustment for study country and cardiovascular risk factors, the hazard ratios of all-cause mortality were 1.58 (95% confidence interval 1.18-2.12) after CHD and 3.13 (95% confidence interval 1.98-4.92) after stroke.

Conclusions-These findings support continuous efforts to promote both primary and secondary prevention of cardiovascular disease.

Catalyst Deactivation on a Two-Stroke Engine

With the legislative demands increasing on recreational vehicles and utility engined applications, the two-stroke engine is facing increasing pressure to meet these requirements. One method of achieving the required reduction is via the introduction of a catalytic converter. The catalytic converter not only has to deal with the characteristically higher CO and HC concentration, but also any oil which is added to lubricate the engine. In a conventional two-stroke engine with a total loss lubrication system, the oil is either scavenged straight out the exhaust port or is entrained, involved in combustion and is later exhausted. This oil can have a significant effect on the performance of the catalyst.
To investigate the oiling effect, three catalytic converters were aged using a 400cm₃ DI two-stroke engine. A finite level of oil was added to the inlet air of the engine to lubricate the internal workings. The oil flow rate is independent of the engine speed and load.

Three catalysts were aged for 50 hours, experiencing a constant space velocity and set engine conditions. The engine was fueled on petrol and later on propane to eliminate the effects, if any, of petrol additives on catalyst deactivation. The oiling rate was varied to investigated deactivation from oil contamination. Post-mortem analysis was performed on the three catalysts. This consisted of a controlled light-off test performed on a catalyst rig, during which period, temperatures were measured and recorded towere aged for 50 hours, experiencing a constant space velocity and set engine conditions. The engine was fueled on petrol and later on propane to eliminate the effects, if any, of petrol additives on catalyst deactivation. The oiling rate was varied to investigated deactivation from oil contamination. Post-mortem analysis was performed on the three catalysts. This consisted of a controlled light-off test performed on a catalyst rig, during which period, temperatures were measured and recorded to find out where deactivation of each catalyst was occurring. The recorded results were all analyzed and these showed that from the measured light-off temperatures the aged catalysts behaved similarly. However the pattern in the light-off was significantly different when the engine was fueled by propane as opposed to gasoline.

Development and Application of Medication Appropriateness Indicators for Persons with Advanced Dementia: A Feasibility Study

Background: No studies have been conducted in the UK context to date that categorise medications in terms of appropriateness for patients with advanced dementia, or that examine medication use in these vulnerable patients.

Objectives: The objectives of this study were to categorise the appropriateness of a comprehensive list of medications and medication classes for use in patients with advanced dementia; examine the feasibility of conducting a longitudinal prospective cohort study to collect clinical and medication use data; and determine the appropriateness of prescribing for nursing home residents with advanced dementia in Northern Ireland (NI), using the categories developed.

Methods: A three-round Delphi consensus panel survey of expert clinicians was used to categorise the appropriateness of medications for patients with advanced dementia [defined as having Functional Assessment Staging (FAST) scores ranging from 6E to 7F]. This was followed by a longitudinal prospective cohort feasibility study that was conducted in three nursing homes in NI. Clinical and medication use for participating residents with advanced dementia (FAST scores ranging from 6E to 7F) were collected and a short test of dementia severity administered. These data were collected at baseline and every 3 months for up to 9 months or until death. For those residents who died during the study period, data were also collected within 14 days of death. The appropriateness ratings from the consensus panel survey were retrospectively applied to residents’ medication data at each data collection timepoint to determine the appropriateness of medications prescribed for these residents.

Results: Consensus was achieved for 87 (90 %) of the 97 medications and medication classes included in the survey. Fifteen residents were recruited to participate in the longitudinal prospective cohort feasibility study, four of whom died during the data collection period. Mean numbers of medications prescribed per resident were 16.2 at baseline, 19.6 at 3 months, 17.4 at 6 months and 16.1 at 9 months. Fourteen residents at baseline were taking at least one medication considered by the consensus panel to be never appropriate, and approximately 25 % of medications prescribed were considered to be never appropriate. Post-death data collection indicated a decrease in the proportion of never appropriate medications and an increase in the proportion of always appropriate medications for those residents who died.

Conclusions: This study is the first to develop and apply medication appropriateness indicators for patients with advanced dementia in the UK setting. The Delphi consensus panel survey of expert clinicians was a suitable method of developing such indicators. It is feasible to collect information on quality of life, functional performance, physical comfort, neuropsychiatric symptoms and cognitive function for this subpopulation of nursing home residents with advanced dementia.

The effect of altering a single component of a rehabilitation programme on the functional recovery of stroke patients: a systematic review and meta-analysis

OBJECTIVE: To evaluate the effect of altering a single component of a rehabilitation programme (e.g. adding bilateral practice alone) on functional recovery after stroke, defined using a measure of activity.

DATA SOURCES: A search was conducted of Medline/Pubmed, CINAHL and Web of Science.

REVIEW METHODS: Two reviewers independently assessed eligibility. Randomized controlled trials were included if all participants received the same base intervention, and the experimental group experienced alteration of a single component of the training programme. This could be manipulation of an intrinsic component of training (e.g. intensity) or the addition of a discretionary component (e.g. augmented feedback). One reviewer extracted the data and another independently checked a subsample (20%). Quality was appraised according to the PEDro scale.

RESULTS: Thirty-six studies (n = 1724 participants) were included. These evaluated nine training components: mechanical degrees of freedom, intensity of practice, load, practice schedule, augmented feedback, bilateral movements, constraint of the unimpaired limb, mental practice and mirrored-visual feedback. Manipulation of the mechanical degrees of freedom of the trunk during reaching and the addition of mental practice during upper limb training were the only single components found to independently enhance recovery of function after stroke.

CONCLUSION: This review provides limited evidence to support the supposition that altering a single component of a rehabilitation programme realises greater functional recovery for stroke survivors. Further investigations are required to determine the most effective single components of rehabilitation programmes, and the combinations that may enhance functional recovery.

Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke

Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.

Glacial cirques as palaeoenvironmental indicators: their potential and limitations

Glacial cirques are armchair-shaped erosional hollows, typified by steep headwalls and, often, overdeepened floors. They reflect former regions of glacier initiation, and their distribution is, therefore, linked to palaeoclimate. Because of this association, cirques can be analysed for the information they provide about past environments, an approach that has a strong heritage, and has seen resurgence over recent years. This paper provides a critical assessment of what cirques can tell us about past environments, and considers their reliability as palaeoenvironmental proxies. Specific focus is placed on information that can be obtained from consideration of cirque distribution, aspect, altitude, and morphometry. The paper highlights the fact that cirques potentially provide information about the style, duration and intensity of former glaciation, as well as information about past temperatures, precipitation gradients, cloud-cover and wind directions. In all, cirques are considered a valuable source of palaeoenvironmental information (if used judiciously), particularly as they are ubiquitous within formerly glaciated mountain ranges globally, thus making regional or even global scale studies possible. Furthermore, cirques often occupy remote and inaccessible regions where other palaeoenvironmental proxies may be limited or lacking.

Identifying marine pelagic ecosystem management objectives and indicators

International policy frameworks such as the Common Fisheries Policy and the European Marine Strategy Framework Directive define high-level strategic goals for marine ecosystems. Strategic goals are addressed via general and operational management objectives. To add credibility and legitimacy to the development of objectives, for this study stakeholders explored intermediate level ecological, economic and social management objectives for Northeast Atlantic pelagic ecosystems. Stakeholder workshops were undertaken with participants being free to identify objectives based on their own insights and needs. Overall 26 objectives were proposed, with 58% agreement in proposed objectives between two workshops. Based on published evidence for pressure-state links, examples of operational objectives and suitable indicators for each of the 26 objectives were then selected. It is argued that given the strong species-specific links of pelagic species with the environment and the large geographic scale of their life cycles, which contrast to demersal systems, pelagic indicators are needed at the level of species (or stocks) independent of legislative region. Pelagic community indicators may be set at regional scale in some cases. In the evidence-based approach used in this study, the selection of species or region specific operational objectives and indicators was based on demonstrated pressure-state links. Hence observed changes in indicators can reliably inform on appropriate management measures

Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603 838 individuals

Background: Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. 

Methods We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. 

Findings We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603 838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528 908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5·1 million person-years (mean 8·5 years), in which 4768 events were recorded, and for stroke was 3·8 million person-years (mean 7·2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (≥55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1·13, 95% CI 1·02-1·26; p=0·02) and incident stroke (1·33, 1·11-1·61; p=0·002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1·30-1·42). We recorded a dose-response association for stroke, with RR estimates of 1·10 (95% CI 0·94-1·28; p=0·24) for 41-48 working hours, 1·27 (1·03-1·56; p=0·03) for 49-54 working hours, and 1·33 (1·11-1·61; p=0·002) for 55 working hours or more per week compared with standard working hours (p_trend<0·0001).

Interpretation Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours.