Comparative trends in hospitalizations for osteoporotic fractures and other frequent diseases between 2000 and 2008

In Switzerland, the number, incidence, and cost of acute hospitalizations for major osteoporotic fractures (MOF) and major cardiovascular events (MCE) increased in both women and men between 2000 and 2008, although the mean length of stay (LOS) was significantly reduced. Similar trend patterns were observed for hip fractures and strokes (decrease) and nonhip fractures and acute myocardial infarctions (increase).

Developmental Brain Dysfunction: Revival and Expansion of Old Concepts Based on New Genetic Evidence

Neurodevelopmental disorders can be caused by many different genetic abnormalities that are individually rare but collectively common. Specific genetic causes, including certain copy number variants and single-gene mutations, are shared among disorders that are thought to be clinically distinct. This evidence of variability in the clinical manifestations of individual genetic variants and sharing of genetic causes among clinically distinct brain disorders is consistent with the concept of developmental brain dysfunction, a term we use to describe the abnormal brain function underlying a group of neurodevelopmental and neuropsychiatric disorders and to encompass a subset of various clinical diagnoses. Although many pathogenic genetic variants are currently thought to be variably penetrant, we hypothesise that when disorders encompassed by developmental brain dysfunction are considered as a group, the penetrance will approach 100%. The penetrance is also predicted to approach 100% when the phenotype being considered is a specific trait, such as intelligence or autistic-like social impairment, and the trait could be assessed using a continuous, quantitative measure to compare probands with non-carrier family members rather than a qualitative, dichotomous trait and comparing probands with the healthy population. Copyright 2013 Elsevier Ltd. All rights reserved.

Life cycle complexity, environmental change and the emerging status of salmonid proliferative kidney disease

P>1. Proliferative kidney disease (PKD) is a disease of salmonid fish caused by the endoparasitic myxozoan, Tetracapsuloides bryosalmonae, which uses freshwater bryozoans as primary hosts. Clinical PKD is characterised by a temperature-dependent proliferative and inflammatory response to parasite stages in the kidney.;2. Evidence that PKD is an emerging disease includes outbreaks in new regions, declines in Swiss brown trout populations and the adoption of expensive practices by fish farms to reduce heavy losses. Disease-related mortality in wild fish populations is almost certainly underestimated because of e.g. oversight, scavenging by wild animals, misdiagnosis and fish stocking.;3. PKD prevalences are spatially and temporally variable, range from 0 to 90-100% and are typically highest in juvenile fish.;4. Laboratory and field studies demonstrate that (i) increasing temperatures enhance disease prevalence, severity and distribution and PKD-related mortality; (ii) eutrophication may promote outbreaks. Both bryozoans and T. bryosalmonae stages in bryozoans undergo temperature- and nutrient-driven proliferation.;5. Tetracapsuloides bryosalmonae is likely to achieve persistent infection of highly clonal bryozoan hosts through vertical transmission, low virulence and host condition-dependent cycling between covert and overt infections. Exploitation of fish hosts entails massive proliferation and spore production by stages that escape the immune response. Many aspects of the parasite's life cycle remain obscure. If infectious stages are produced in all hosts then the complex life cycle includes multiple transmission routes.;6. Patterns of disease outbreaks suggest that background, subclinical infections exist under normal environmental conditions. When conditions change, outbreaks may then occur in regions where infection was hitherto unsuspected.;7. Environmental change is likely to cause PKD outbreaks in more northerly regions as warmer temperatures promote disease development, enhance bryozoan biomass and increase spore production, but may also reduce the geographical range of this unique multihost-parasite system. Coevolutionary dynamics resulting from host-parasite interactions that maximise fitness in previous environments may pose problems for sustainability, particularly in view of extensive declines in salmonid populations and degradation of many freshwater habitats.

International Service-Learning and the Development of Civic Identity: Understanding the Role of Short-Term International Service-Learning and its Influence on the Development of Civic Identity in College Students Using a Mixed Methodological Approach

Higher education has a responsibility to educate a democratic citizenry and recent research indicates civic engagement is on the decline in the United States. Through a mixed methodological approach, I demonstrate that the potential exists for well structured short-term international service-learning programming to develop college students’ civic identities. Quantitative analysis of questionnaire data, collected from American college students immediately prior to their participation in a short-term service-learning experience in Northern Ireland and again upon their return to the United States, revealed increases in civic accountability, political efficacy, justice oriented citizenship, and service-learning. Subsequent qualitative analysis of interview transcripts, student journals, and field notes suggested that facilitated critical reflection before, during, and after the experience promoted transformational learning. Emergent themes included: (a) responsibilities to others, (b) the value of international service-learning, (c) crosspollination of ideas, (d) stepping outside the daily routine to facilitate divergent thinking, and (e) the necessity of precursory thinking for sustaining transformations in thinking. The first theme, responsibilities to others, was further divided into subthemes of thinking beyond oneself, raising awareness of responsibility to others, and voting responsibly.

Processes Regulating the Initiation and Postejaculatory Resumption of Copulatory Behavior in Male Hamsters

Studies using factor analysis have helped describe the organization of copulatory behavior in male rodents. However, the focus of these studies on a few traditional measures may have limited their results. To test this possibility, 74 sexually-experienced male hamsters were observed as they copulated with stimulus females. The measures collected exceeded the conventional ones in number, variety and independence. The factor analysis of these data revealed a structure with seven factors collectively accounting for 80% of the variance. Most resembled the factors in previous reports, reinforcing the contributions that the processes suggested by these factors make to the organization,of male behavior. But several other factors were more novel, possibly reflecting the use of measures that were novel or revised for greater independence. The most interesting of these were two factors focusing on early steps in the progression leading to ejaculation. Importantly, both incorporated measures from each of the three copulatory series that were observed. Past work suggests that independent processes control the times required to initiate copulation and later resume it after an ejaculation. In contrast, these results suggest the existence of two processes, each of which contributes to both the initiation and reinitiation of copulation. (C) 2014 Elsevier B.V. All rights reserved.

Exogenous gonadotropins have little impact on follicular but considerable effect on serum cytokine concentrations – a comparison between Natural Cycle and stimulated IVF using a multiplexed assay platform

Introduction: Throughout follicular growth and subsequent corpus luteum formation the leukocyte number increases and follicular vascularisation changes. These processes are enhanced under exogenous stimulation with gonadotropins. Cytokines released by leukocytes contribute to further recruitment and vascularisation of the follicle, and they play an important role in regulating ovarian steroidogenesis by influencing theca and granulosa–lutein cell function. Changes in cytokine and vascular endothelial growth factor (VEGF) concentrations in the ovary as a consequence of gonadotropin stimulation may negatively influence oocyte quality. In this project we have compared the intrafollicular production of inflammatory cytokines and growth factors between natural IVF cycles (NC) and classical, gonadotropin-stimulated IVF cycles (gsIVF). Material and Methods: Serum on the day of oocyte retrieval and follicular fluid (FF) were collected in 37 NC and 39 gsIVF cycles. Thirteen women within this population underwent one NC and one gsIVF cycle each. A total of 14 cytokines from Bio-Plex panels I and II were determined in matched serum and FF samples using Luminex xMAP technology on the Bio-Plex(R) platform, using the serum protocol. Results: Tumour necrosis factor-alpha, RANTES, eotaxin and interferon-gamma-induced protein-10 levels were lower in FF than in serum, and thus not further investigated. Interleukin (IL)-6, -8, -10, -15, -18, monocyte chemotactic protein-1 (MCP-1), VEGF and leukaemia inhibitory factor (LIF) showed higher median concentrations in FF than in serum, indicating possible ovarian production. Moreover, most of these showed higher evels in the gsIVF than in the NC groups in the serum, but not in the follicular fluid. IL-8 was reduced in gsIVF cycles. Conclusion: The fact that serum but not FF levels of the studied cytokines were higher in the stimulated than in the natural cycles can be attributed to the increased number of active follicles present after controlled ovarian stimulation.

Management, feeding, production, reproduction and udder health on organic and conventional Swiss dairy farms

Organic dairy farms (OP; n=60) and conventional dairy farms (integrated production, IP; n=60), matched in size, location, and agricultural zone (altitude), were studied for possible differences in management, feeding, production, reproduction and udder health. OP and IP farms were similar in size (17.7 and 16.9 ha), milk quota (65900 and 70,000 kg/year), cow number (14 and 15), cow age (5.3 and 5.2 years), housing of cows of the Simmental x Red Holstein or Holstein breeds (87 and 75%; 45 and 60%), but differed significantly with respect to loose housing systems (18 and 7%), outside paddocks (98 and 75%), energy-corrected 305-d milk yield (5,695 and 6,059 kg), milk protein content (31.8 and 32.7 g/kg), use of bucket milking systems (73 and 33%), observance of regular (12-h) milking intervals (47 and 68%), routine application of the California-Mastitis-Test (10 and 28%), teat dipping after milking (25 and 43%) and blanket dry cow treatments (0 and 45%). Milk somatic cell counts on OP and IP farms (119 000 and 117,000/mL) and reproduction data were similar and there were no significant differences between OP and IP farms as concerns available feeds, planning and management of feeding. Alternative veterinary treatments were used more often on OP than IP farms (55 and 17%). Main causes for cow replacements on OP and IP farms were fertility disorders (both 45%), age (40 and 42%), sale (30 and 37%) and udder health (35 and 13%).Between OP and IP Swiss dairy farms thus relatively few larger differences were found.

Evaluation of late results in breast reconstruction by latissimus dorsi flap and prosthesis implantation

BACKGROUND: Breast reconstruction by latissimus dorsi myocutaneous flap in combination with a prosthesis is a widely used, well-established procedure. Short- and medium-term evaluation after this procedure is well described in the literature, but there have been no evaluations of the late course (over 10 years) published until now. METHODS: In a retrospective study, 68 patients operated on by means of this technique at the authors' institution from 1981 to 1993 resulting in a minimal follow-up of 10 years were included. Patients were invited to an interrogation, clinical examination, and photographic documentation (n = 51). Incidence of late flap or prosthesis-related complications, number of and indications for corrective procedures, and the correlation of the patients' subjective judgment and objective results in the late course have been the main interest of the authors' survey. RESULTS: The authors found that 50 percent of the patients needed a late reoperation for change or removal of the prosthesis. Seven (10 percent) of 68 patients needed a definitive removal of the implant in the late course. Assessment of the photographic documentation of the late result by four nonprofessionals showed that the objective aesthetic results of a considerable number of the authors' reconstructions were not sufficient. CONCLUSION: The procedure combines two basic techniques of reconstructive surgery, the soft-tissue restoration by a pedicled flap as the autologous reconstructive component and the volume reconstruction by prosthesis. Therefore, these patients are subject to a cumulation of the basic morbidity of the two techniques. The authors conclude that the indication for this procedure should be restricted to patients not qualifying for "pure" reconstructive techniques.

Chronic excessive erythrocytosis induces endothelial activation and damage in mouse brain

Excessive erythrocytosis results in severely increased blood viscosity, which may have significant detrimental effects on endothelial cells and, ultimately, function of the vascular endothelium. Because blood-brain barrier stability is crucial for normal physiological function, we used our previously characterized erythropoietin-overexpressing transgenic (tg6) mouse line (which has a hematocrit of 0.8-0.9) to investigate the effect of excessive erythrocytosis on vessel number, structure, and integrity in vivo. These mice have abnormally high levels of nitric oxide (NO), a potent proinflammatory molecule, suggesting altered vascular permeability and function. In this study, we observed that brain vessel density of tg6 mice was significantly reduced (16%) and vessel diameter was significantly increased (15%) compared with wild-type mice. Although no significant increases in vascular permeability under normoxic or acute hypoxic conditions (8% O2 for 4 h) were detected, electron-microscopic analysis revealed altered morphological characteristics of the tg6 endothelium. Tg6 brain vascular endothelial cells appeared to be activated, with increased luminal protrusions reminiscent of ongoing inflammatory processes. Consistent with this observation, we detected increased levels of intercellular adhesion molecule-1 and von Willebrand factor, markers of endothelial activation and damage, in brain tissue. We propose that chronic excessive erythrocytosis and sustained high hematocrit cause endothelial damage, which may, ultimately, increase susceptibility to vascular disease.

A MULTILEVEL MODEL TO ADDRESS BATCH EFFECTS IN COPY NUMBER ESTIMATION USING SNP ARRAYS

Submicroscopic changes in chromosomal DNA copy number dosage are common and have been implicated in many heritable diseases and cancers. Recent high-throughput technologies have a resolution that permits the detection of segmental changes in DNA copy number that span thousands of basepairs across the genome. Genome-wide association studies (GWAS) may simultaneously screen for copy number-phenotype and SNP-phenotype associations as part of the analytic strategy. However, genome-wide array analyses are particularly susceptible to batch effects as the logistics of preparing DNA and processing thousands of arrays often involves multiple laboratories and technicians, or changes over calendar time to the reagents and laboratory equipment. Failure to adjust for batch effects can lead to incorrect inference and requires inefficient post-hoc quality control procedures that exclude regions that are associated with batch. Our work extends previous model-based approaches for copy number estimation by explicitly modeling batch effects and using shrinkage to improve locus-specific estimates of copy number uncertainty. Key features of this approach include the use of diallelic genotype calls from experimental data to estimate batch- and locus-specific parameters of background and signal without the requirement of training data. We illustrate these ideas using a study of bipolar disease and a study of chromosome 21 trisomy. The former has batch effects that dominate much of the observed variation in quantile-normalized intensities, while the latter illustrates the robustness of our approach to datasets where as many as 25% of the samples have altered copy number. Locus-specific estimates of copy number can be plotted on the copy-number scale to investigate mosaicism and guide the choice of appropriate downstream approaches for smoothing the copy number as a function of physical position. The software is open source and implemented in the R package CRLMM available at Bioconductor (http:www.bioconductor.org).

Regional structural characteristics of bovine periodontal ligament samples and their suitability for biomechanical tests

Mechanical testing of the periodontal ligament requires a practical experimental model. Bovine teeth are advantageous in terms of size and availability, but information is lacking as to the anatomy and histology of their periodontium. The aim of this study, therefore, was to characterize the anatomy and histology of the attachment apparatus in fully erupted bovine mandibular first molars. A total of 13 teeth were processed for the production of undecalcified ground sections and decalcified semi-thin sections, for NaOH maceration, and for polarized light microscopy. Histomorphometric measurements relevant to the mechanical behavior of the periodontal ligament included width, number, size and area fraction of blood vessels and fractal analysis of the two hard-soft tissue interfaces. The histological and histomorphometric analyses were performed at four different root depths and at six circumferential locations around the distal and mesial roots. The variety of techniques applied provided a comprehensive view of the tissue architecture of the bovine periodontal ligament. Marked regional variations were observed in width, surface geometry of the two bordering hard tissues (cementum and alveolar bone), structural organization of the principal periodontal ligament connective tissue fibers, size, number and numerical density of blood vessels in the periodontal ligament. No predictable pattern was observed, except for a statistically significant increase in the area fraction of blood vessels from apical to coronal. The periodontal ligament width was up to three times wider in bovine teeth than in human teeth. The fractal analyses were in agreement with the histological observations showing frequent signs of remodeling activity in the alveolar bone - a finding which may be related to the magnitude and direction of occlusal forces in ruminants. Although samples from the apical root portion are not suitable for biomechanical testing, all other levels in the buccal and lingual aspects of the mesial and distal roots may be considered. The bucco-mesial aspect of the distal root appears to be the most suitable location.

Development of specifications for the superpave simple performance tests

This study describes the development and establishment of a proposed Simple Performance Test (SPT) specification in order to contribute to the asphalt materials technology in the state of Michigan. The properties and characteristic of materials, performance testing of specimens, and field analyses are used in developing draft SPT specifications. These advanced and more effective specifications should significantly improve the qualities of designed and constructed hot mix asphalt (HMA) leading to improvement in pavement life in Michigan. The objectives of this study include the following: 1) using the SPT, conduct a laboratory study to measure the parameters including the dynamic modulus terms (E*/sinϕ and E*) and the flow number (Fn) for typical Michigan HMA mixtures, 2) correlate the results of the laboratory study to field performance as they relate to flexible pavement performance (rutting, fatigue, and low temperature cracking), and 3) make recommendations for the SPT criteria at specific traffic levels (e.g. E3, E10, E30), including recommendations for a draft test specification for use in Michigan. The specification criteria of dynamic modulus were developed based upon field rutting performance and contractor warranty criteria.

RISK OF SHUNT-DEPENDENT HYDROCEPHALUS AFTER OCCLUSION OF RUPTURED INTRACRANIAL ANEURYSMS BY SURGICAL CLIPPING OR ENDOVASCULAR COILING: A SINGLE-INSTITUTION SERIES AND META-ANALYSIS

OBJECTIVE: To compare the risk of shunt-dependent hydrocephalus after treatment of ruptured intracranial aneurysms by clipping versus coiling. METHODS: We analyzed 596 patients prospectively added to our database from July of 1999 to November of 2005 concerning the risk of shunt dependency after clipping versus coiling. Factors analyzed included age; sex; Hunt and Hess grade; Fisher grade; acute hydrocephalus; intraventricular hemorrhage; angiographic vasospasm; and number, size, and location of aneurysms. In addition, a meta-analysis of available data from the literature was performed identifying four studies with quantitative data on the frequency of clip, coil, and shunt dependency. RESULTS: The institutional series revealed Hunt and Hess grade, Fisher grade, acute hydrocephalus, intraventricular hemorrhage, and angiographic vasospasm as significant (P < 0.05) risk factors for shunt dependency after a univariate analysis. In a multivariate logistic regression analysis, we isolated intraventricular hemorrhage, acute hydrocephalus, and angiographic vasospasm as independent, significant risk factors for shunt dependency. The meta-analysis, including the current data, revealed a significantly higher risk for shunt dependency after coiling than after clipping (P = 0.01). CONCLUSION: Clipping of a ruptured aneurysm may be associated with a lower risk for developing shunt dependency, possibly by clot removal. This might influence long-term outcome and surgical decision making.

Small-scale timber stand management techniques : a case study of woodlots in Isangati, Tanzania

Small-scale village woodlots of less than 0.5ha are the preferred use of land for local farmers with extra land in the village of Isangati, a small community located in the southern highlands of Tanzania. Farmers view woodlots as lucrative investments that do not involve intensive labor or time. The climate is ideal for the types of trees grown and the risks are minimal with no serious threats from insects, fires, thieves, or grazing livestock. It was hypothesized that small-scale village woodlot owners were not maximizing timber outputs with their current timber stand management and harvesting techniques. Personal interviews were conducted over a five month period and field data was collected at each farmer’s woodlots over a seven month period. Woodlot field data included woodlot size, number of trees, tree species, tree height, dbh, age, and spacing. The results indicated that the lack of proper woodlot management techniques results in failure to fully capitalize on the investment of woodlots. While farmers should continue with their current harvesting rotations, some of the reasons for not maximizing tree growth include close spacing (2m x 2m), no tree thinning, extreme pruning (60% of tree), and little to no weeding. Through education and hands-on woodlot management workshops, the farmers could increase their timber output and value of woodlots.