Parental use of corporal punishment in Europe: intersection between public health and policy.
Studies have linked the use of corporal punishment of children to the development of mental health disorders. Despite the recommendation of international governing bodies for a complete ban of the practice, there is little European data available on the effects of corporal punishment on mental health and the influence of laws banning corporal punishment. Using data from the School Children Mental Health Europe survey, the objective of this cross-sectional study was to examine the prevalence and legal status of corporal punishment across six European countries and to evaluate the association between parental use of corporal punishment and children's mental health. The study found that odds of having parents who reported using occasional to frequent corporal punishment were 1.7 times higher in countries where its use is legal, controlling for socio-demographic factors. Children with parents who reported using corporal punishment had higher rates of both externalized and internalized mental health disorders.


In vivo magnetic resonance imaging of immune cells in the central nervous system with superparamagnetic antibodies.
We developed a novel MRI technique to image immune cell location and homing in vivo to the central nervous system (CNS). Superparamagnetic antibodies specific for cell surface markers allowed imaging of CD4+ T cells, CD8+ T cells, and Mac1+ cells in the CNS of mice infected with Theiler's murine encephalomyelitis virus (TMEV) and in mice with experimental autoimmune encephalomyelitis (EAE). Superparamagnetic antibodies have excellent T2, T2*, and good T1 relaxation properties, which makes them ideal MRI contrast materials. Immunohistochemistry of corresponding sections confirmed the specificity of the technique to detect immune cell types in the CNS. This powerful technique has potential to image any cell with unique surface antigens. Because superparamagnetic antibodies similar to those used in the study are approved for human use, the in vivo MRI technique we have described could be developed for human use.


Effects of HuR downregulation on anaplastic thyroid cancer cells.
Anaplastic thyroid cancer (ATC) constitutes one of the most aggressive types of human solid cancer, and is characterized by the absence of thyroid differentiation features and a marked degree of invasiveness. We have previously demonstrated that the RNA-binding protein Hu antigen R (HuR) is overexpressed in thyroid carcinoma; thus, the biological role of this RNA-binding protein was investigated in the present study using the ATC cell lines SW1736 and 8505C. In both cell lines, HuR protein levels were higher compared with in the non-tumorigenic thyroid cell line Nthy-ori-3.1. HuR silencing by RNA interference in both ATC cell lines decreased cell viability, increased apoptosis rates and reduced the capability to form colonies in soft agar. Thus, HuR plays an important role in the proliferation and aggressiveness of ATC cells. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) was able to reduce the viability of ATC cells. The results demonstrated that SAHA was able to decrease HuR expression in SW1736 and 8505C cells. Furthermore, since it is known that the transcription factor nuclear factor (NF)-κB modulates HuR expression, whether SAHA affects the nuclear (active) fraction of NF-κB in ATC cells was investigated. The data suggested that SAHA decreases ATC cell viability by reducing the active form of NF-κB, which, in turn, modulates HuR expression.


Proposed changes to the hospital-medical staff relationship to improve quality of care.
Medical staff attorney Snelson answers the Colloquium's charge, "What exactly has to change in the hospital-medical staff relationship for health care quality to be improved?" Her response emphasizes the logic of having clinicians vested with authority to establish policies concerning the clinical decision-making. The article discusses the cases defining the medical staff bylaws as contractual in nature, and the problem of hospital attorneys demanding unilateral amendments to bylaws. Bylaw clauses that would chill medical opinion and communication or denigrate clinical recommendations are discussed. Ms. Snelson advocates for the inclusion of the medical staff organization in exclusive contract and other clinical decision-making, and includes sample bylaw language enacting her recommendations.


Growth after adenotonsillectomy for obstructive sleep apnea: an RCT.
Adenotonsillectomy for obstructive sleep apnea syndrome (OSAS) may lead to weight gain, which can have deleterious health effects when leading to obesity. However, previous data have been from nonrandomized uncontrolled studies, limiting inferences. This study examined the anthropometric changes over a 7-month interval in a randomized controlled trial of adenotonsillectomy for OSAS, the Childhood Adenotonsillectomy Trial. A total of 464 children who had OSAS (average apnea/hypopnea index [AHI] 5.1/hour), aged 5 to 9.9 years, were randomized to Early Adenotonsillectomy (eAT) or Watchful Waiting and Supportive Care (WWSC). Polysomnography and anthropometry were performed at baseline and 7-month follow-up. Multivariable regression modeling was used to predict the change in weight and growth indices. Interval increases in the BMI z score (0.13 vs. 0.31) was observed in both the WWSC and eAT intervention arms, respectively, but were greater with eAT (P < .0001). Statistical modeling showed that BMI z score increased significantly more in association with eAT after considering the influences of baseline weight and AHI. A greater proportion of overweight children randomized to eAT compared with WWSC developed obesity over the 7-month interval (52% vs. 21%; P < .05). Race, gender, and follow-up AHI were not significantly associated with BMI z score change. eAT for OSAS in children results in clinically significant greater than expected weight gain, even in children overweight at baseline. The increase in adiposity in overweight children places them at further risk for OSAS and the adverse consequences of obesity. Monitoring weight, nutritional counseling, and encouragement of physical activity should be considered after eAT for OSAS.


The role of (15)N CSA and CSA/dipole cross-correlation in (15)N relaxation in solid proteins.
The influence of the (15)N CSA on (15)N longitudinal relaxation is investigated for an amide group in solid proteins in powder form under MAS. This contribution is determined to be typically 20-33% of the overall longitudinal relaxation rate, at 11.74 and 16.45 T, respectively. The improved treatment is used to analyze the internal dynamics in the protein Crh, in the frame of a motional model of diffusion in a cone, using the explicit average sum approach. Significant variations with respect to the determined dynamics parameters are observed when properly accounting for the contribution of (15)N CSA fluctuations. In general, the fit of experimental data including CSA led to the determination of diffusion times (tau(w)) which are longer than when considering only an (15)N-(1)H dipolar relaxation mechanism. CSA-Dipole cross-correlation is shown to play little or no role in protonated solids, in direct contrast to the liquid state case.


What to do when you question cardiac troponin values.
High-sensitivity cardiac troponin assays enable cardiac troponin measurement with a high degree of analytical sensitivity and a low level of analytical imprecision at the low measuring range. One of the most important advantages of these new assays is that they allow novel, more rapid approaches for ruling in or ruling out acute myocardial infarctions. The increase in the early diagnostic sensitivity of high-sensitivity cardiac troponin assays comes at the cost of a reduced acute myocardial infarction specificity of the biomarker, because more patients with other causes of acute or chronic myocardial injury without overt myocardial ischaemia are detected than with previous cardiac troponin assays. Increased troponin concentrations that do not fit with the clinical presentation are seen in the daily routine, mainly as a result of a variety of pathologies, and if tested in the same sample, even discrepancies between high-sensitivity cardiac troponin I and troponin T test results may sometimes be found as well. In addition, analytically false-positive test results occasionally may occur since no assay is perfect. In this review, we summarise the biochemical, pathophysiological and analytical background of the work-up for such a clinical setting.


[Interactive mortality atlas in Andalusia, Spain (AIMA)].
Until now, mortality atlases have been static. Most of them describe the geographical distribution of mortality using count data aggregated over time and standardized mortality rates. However, this methodology has several limitations. Count data aggregated over time produce a bias in the estimation of death rates. Moreover, this practice difficult the study of temporal changes in geographical distribution of mortality. On the other hand, using standardized mortality hamper to check differences in mortality among groups. The Interactive Mortality Atlas in Andalusia (AIMA) is an alternative to conventional static atlases. It is a dynamic Geographical Information System that allows visualizing in web-site more than 12.000 maps and 338.00 graphics related to the spatio-temporal distribution of the main death causes in Andalusia by age and sex groups from 1981. The objective of this paper is to describe the methods used for AIMA development, to show technical specifications and to present their interactivity. The system is available from the link products in www.demap.es. AIMA is the first interactive GIS that have been developed in Spain with these characteristics. Spatio-temporal Hierarchical Bayesian Models were used for statistical data analysis. The results were integrated into web-site using a PHP environment and a dynamic cartography in Flash. Thematic maps in AIMA demonstrate that the geographical distribution of mortality is dynamic, with differences among year, age and sex groups. The information nowadays provided by AIMA and the future updating will contribute to reflect on the past, the present and the future of population health in Andalusia.


Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents.
Several studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer's disease. We previously reported chronic ingestion of saturated fatty acids (SFA) compromises blood-brain barrier (BBB) integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA's. Wild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG) and amyloid-β enriched apolipoprotein (apo)-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy. Atorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble). Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis. Our findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.


Geriatrics Education Team Model Results in Sustained Geriatrics Training in 15 Residency and Fellowship Programs and Scholarship.
Caring for the growing elderly population will require specialty and subspecialty physicians who have not completed geriatric medicine fellowship training to participate actively in patient care. To meet this workforce demand, a sustainable approach to integrating geriatrics into specialty and subspecialty graduate medical education training is needed. This article describes the use of a geriatrics education team (GET) model to develop, implement, and sustain specialty-specific geriatrics curricula using a systematic process of team formation and needs assessment through evaluation, with a unique focus on developing curricular interventions that are meaningful to each specialty and satisfy training, scholarship, and regulatory requirements. The GET model and associated results from 15 specialty residency and fellowship training programs over a 4-year period include 93% curriculum sustainability after initial implementation, more than half of the programs introducing additional geriatrics education, and more than 80% of specialty GETs fulfilling their scholarship requirements through their curriculum dissemination. Win-wins and barriers encountered in using the GET model, along with the model's efficacy in curriculum development, sustainability, and dissemination, are summarized.


The Chloroplast Genome of Passiflora edulis (Passifloraceae) Assembled from Long Sequence Reads: Structural Organization and Phylogenomic Studies in Malpighiales.
The family Passifloraceae consists of some 700 species classified in around 16 genera. Almost all its members belong to the genus Passiflora. In Brazil, the yellow passion fruit (Passiflora edulis) is of considerable economic importance, both for juice production and consumption as fresh fruit. The availability of chloroplast genomes (cp genomes) and their sequence comparisons has led to a better understanding of the evolutionary relationships within plant taxa. In this study, we obtained the complete nucleotide sequence of the P. edulis chloroplast genome, the first entirely sequenced in the Passifloraceae family. We determined its structure and organization, and also performed phylogenomic studies on the order Malpighiales and the Fabids clade. The P. edulis chloroplast genome is characterized by the presence of two copies of an inverted repeat sequence (IRA and IRB) of 26,154 bp, each separating a small single copy region of 13,378 bp and a large single copy (LSC) region of 85,720 bp. The annotation resulted in the identification of 105 unique genes, including 30 tRNAs, 4 rRNAs, and 71 protein coding genes. Also, 36 repetitive elements and 85 SSRs (microsatellites) were identified. The structure of the complete cp genome of P. edulis differs from that of other species because of rearrangement events detected by means of a comparison based on 22 members of the Malpighiales. The rearrangements were three inversions of 46,151, 3,765 and 1,631 bp, located in the LSC region. Phylogenomic analysis resulted in strongly supported trees, but this could also be a consequence of the limited taxonomic sampling used. Our results have provided a better understanding of the evolutionary relationships in the Malpighiales and the Fabids, confirming the potential of complete chloroplast genome sequences in inferring evolutionary relationships and the utility of long sequence reads for generating very accurate biological information.


Flow cytometry: basic principles and applications.
Flow cytometry is a sophisticated instrument measuring multiple physical characteristics of a single cell such as size and granularity simultaneously as the cell flows in suspension through a measuring device. Its working depends on the light scattering features of the cells under investigation, which may be derived from dyes or monoclonal antibodies targeting either extracellular molecules located on the surface or intracellular molecules inside the cell. This approach makes flow cytometry a powerful tool for detailed analysis of complex populations in a short period of time. This review covers the general principles and selected applications of flow cytometry such as immunophenotyping of peripheral blood cells, analysis of apoptosis and detection of cytokines. Additionally, this report provides a basic understanding of flow cytometry technology essential for all users as well as the methods used to analyze and interpret the data. Moreover, recent progresses in flow cytometry have been discussed in order to give an opinion about the future importance of this technology.


High-intensity interval training and hyperoxia during chemotherapy: A case report about the feasibility, safety and physical functioning in a colorectal cancer patient.
We conducted a case study to examine the feasibility and safety of high-intensity interval training (HIIT) with increased inspired oxygen content in a colon cancer patient undergoing chemotherapy. A secondary purpose was to investigate the effects of such training regimen on physical functioning. A female patient (51 years; 49.1 kg; 1.65 m; tumor stage: pT3, pN2a (5/29), pM1a (HEP), L0, V0, R0) performed 8 sessions of HIIT (5 × 3 minutes at 90% of Wmax, separated by 2 minutes at 45% Wmax) with an increased inspired oxygen fraction of 30%. Patient safety, training adherence, cardiorespiratory fitness (peak oxygen uptake and maximal power output during an incremental cycle ergometer test), autonomous nervous function (i.e., heart rate variability during an orthostatic test) as well as questionnaire-assessed quality of life (EORTC QLQ-C30) were evaluated before and after the intervention.No adverse events were reported throughout the training intervention and a 3 months follow-up. While the patient attended all sessions, adherence to total training time was only 51% (102 of 200 minutes; mean training time per session 12:44 min:sec). VO2peak and Wmax increased by 13% (from 23.0 to 26.1 mL min kg) and 21% (from 83 to 100 W), respectively. Heart rate variability represented by the root mean squares of successive differences both in supine and upright positions were increased after the training by 143 and 100%, respectively. The EORTC QLQ-C30 score for physical functioning (7.5%) as well as the global health score (10.7%) improved, while social function decreased (17%). Our results show that a already short period of HIIT with concomitant hyperoxia was safe and feasible for a patient undergoing chemotherapy for colon cancer. Furthermore, the low overall training adherence of only 51% and an overall low training time per session (∼13 minutes) was sufficient to induce clinically meaningful improvements in physical functioning. However, this case also underlines that intensity and/or length of the HIIT-bouts might need further adjustments to increase training compliance.


Pain in Endometriosis.
Endometriosis is a chronic and debilitating condition affecting ∼10% of women. Endometriosis is characterized by infertility and chronic pelvic pain, yet treatment options remain limited. In many respects this is related to an underlying lack of knowledge of the etiology and mechanisms contributing to endometriosis-induced pain. Whilst many studies focus on retrograde menstruation, and the formation and development of lesions in the pathogenesis of endometriosis, the mechanisms underlying the associated pain remain poorly described. Here we review the recent clinical and experimental evidence of the mechanisms contributing to chronic pain in endometriosis. This includes the roles of inflammation, neurogenic inflammation, neuroangiogenesis, peripheral sensitization and central sensitization. As endometriosis patients are also known to have co-morbidities such as irritable bowel syndrome and overactive bladder syndrome, we highlight how common nerve pathways innervating the colon, bladder and female reproductive tract can contribute to co-morbidity via cross-organ sensitization.


Pro-angiogenic CD14(++) CD16(+) CD163(+) monocytes accelerate the in vitro endothelialization of soft hydrophobic poly (n-butyl acrylate) networks.
As the majority of the polymers used as cardiovascular grafts so far do not match the elasticity of human arteries (100-1000kPa) and the required endothelialization, a multifunctional material approach is needed to allow the adjustment of the mechanical properties while at the same time exhibiting a haemocompatible surface. Recently soft poly(n-butyl acrylate) networks (cPnBA) with adjustable mechanical properties were introduced as candidate materials with a surface that can be endothelialized. In this study, angiogenically stimulated intermediate CD163(+) monocytes/macrophages (aMO2) were utilized as a cellular cytokine release system to realize the functional endothelialization of the hydrophobic cPnBA surface. We investigated the influence of co-cultured aMO2 on the morphology, density and cytokine secretion of human umbilical venous endothelial cells (HUVEC) seeded on cPnBA with an elastic modulus of around 250kPa (cPnBA0250). A functional confluent HUVEC monolayer could be developed in the co-culture within 3days. In contrast, the HUVEC in the monoculture exhibited stress fibres, broadened marginal filament bands and significantly more and larger cell-free areas in the monolayer, indicating incomplete cell-substrate binding. Remarkably, a functional confluent monolayer formation could only be achieved in co-cultures; it did not develop with the sole supplementation of recombinant VEGF-A(165) to the HUVEC monocultures (unpublished data). The study demonstrated the multifunctional potential of cPnBA in combination with aMO2 as a cellular cytokine release system, adapting their secretion to the demand of HUVEC. In this way, a functional confluent monolayer could be generated within 3days.


Multigene expression profile testing in breast cancer: is there a role for family physicians?
Family physicians (fps) play a role in aspects of personalized medicine in cancer, including assessment of increased risk because of family history. Little is known about the potential role of fps in supporting cancer patients who undergo tumour gene expression profile (gep) testing. We conducted a mixed-methods study with qualitative and quantitative components. Qualitative data from focus groups and interviews with fps and cancer specialists about the role of fps in breast cancer gep testing were obtained during studies conducted within the pan-Canadian canimpact research program. We determined the number of visits by breast cancer patients to a fp between the first medical oncology visit and the start of chemotherapy, a period when patients might be considering results of gep testing. The fps and cancer specialists felt that ordering gep tests and explaining the results was the role of the oncologist. A new fp role was identified relating to the fp-patient relationship: supporting patients in making adjuvant therapy decisions informed by gep tests by considering the patient's comorbid conditions, social situation, and preferences. Lack of fp knowledge and resources, and challenges in fp-oncologist communication were seen as significant barriers to that role. Between 28% and 38% of patients visited a fp between the first oncology visit and the start of chemotherapy. Our findings suggest an emerging role for fps in supporting patients who are making adjuvant treatment decisions after receiving the results of gep testing. For success in this new role, education and point-of-care tools, together with more effective communication strategies between fps and oncologists, are needed.


Non-Steroidal Anti-Inflammatory Drug Use and Genomic DNA Methylation in Blood.
Non-steroidal anti-inflammatory drug (NSAID) use is associated with decreased risk of some cancers. NSAID use modulates the epigenetic profile of normal colonic epithelium and may reduce risk of colon cancer through this pathway; however, the effect of NSAID use on the DNA methylation profile of other tissues including whole blood has not yet been examined. Using the Sister Study cohort, we examined the association between NSAID usage and whole genome methylation patterns in blood DNA. Blood DNA methylation status across 27,589 CpG sites was evaluated for 871 women using the Illumina Infinium HumanMethylation27 Beadchip, and in a non-overlapping replication sample of 187 women at 485,512 CpG sites using the Infinium HumanMethylation450 Beadchip. We identified a number of CpG sites that were differentially methylated in regular, long-term users of NSAIDs in the discovery group, but none of these sites were statistically significant in our replication group. We found no replicable methylation differences in blood related to NSAID usage. If NSAID use does effect blood DNA methylation patterns, differences are likely small.


Livestock grazing affects the egg size of an insectivorous passerine.
Livestock grazing is a major driver of ecosystem change, and has been associated with significant declines in various bird species worldwide. In Britain, there is particular concern that severe grazing pressure is deleteriously affecting vegetation and birds in upland regions. However, the mechanism by which grazing affects birds is unclear. Here, we report for the first time, to our knowledge, that sheep grazing pressure affects the egg size of a common upland passerine: the meadow pipit Anthus pratensis. We manipulated sheep stocking densities in a replicated field experiment, and found that plots with the highest stocking density contained nests with the smallest eggs, and that plots with low stocking density contained nests with the largest eggs. However, eggs laid in ungrazed plots were also small, suggesting that either too many sheep or their removal from upland areas might have a detrimental effect on pipit egg size. We found no significant effect on fledging success but the reduced post-fledging survival of young from smaller eggs, as seen in other studies, could partly explain declines in upland birds.


The Road Less Traveled: Alternative Pathways for Action-Verb Processing in Parkinson's Disease.
Action verbs are critically embodied in motor brain networks. In Parkinson's disease (PD), damage to the latter compromises access to such words. However, patients are not fully incapable of processing them, as their performance is far from floor level. Here we tested the hypothesis that action-verb processing in PD may rely on alternative disembodied semantic circuits. Seventeen PD patients and 15 healthy controls listened to action verbs and nouns during functional MRI scanning. Using cluster-mass analysis with a permutation test, we assessed task-related functional connectivity considering seeds differentially engaged by action and non-action words (namely, putamen and M1 versus posterior superior temporal lobe, respectively). The putamen seed showed reduced connectivity within the basal ganglia in patients for both lexical categories. However, only action verbs recruited different cortical networks in each group. Specifically, the M1 seed exhibited more anterior connectivity for controls and more posterior connectivity for patients, with no differences in the temporal seed. Moreover, the patients' level of basal ganglia atrophy positively correlated with their reliance on M1-posterior connectivity during action-verb processing. PD patients seem to have processed action verbs via non-motor cortical networks subserving amodal semantics. Such circuits may afford alternative pathways to process words when default embodied mechanisms are disturbed. Moreover, the greater the level of basal ganglia atrophy, the greater the patients' reliance on this alternative route. Our findings offer new insights into differential neurofunctional mechanisms recruited to process action semantics in PD.


Vaginal hygiene practices and perceptions among women in the urban Northeast.
To inform development of an intervention to decrease vaginal douching among Latinas, we conducted a survey of 335 women aged 16-45 years in primary care offices in the urban Northeast, including many Hispanic women (59.7%). About a third (30.7%) indicated that they had never douched. Of women who had ever douched (n = 235), 51.1% indicated they no longer douche. Women reported using a variety of products for douching and non-douching hygiene, including U.S.-made and imported commercial products as well as traditional products. Compared to Black women, more Hispanic women reported never douching and use of imported products. More positive beliefs about the benefits of douching and its safety were reported by women who currently douche. Health care providers should be aware that women may be using imported and traditional products, the safety of which is unknown. Advice about douching from health care providers may be effective for some women in helping them choose to stop or not initiate the practice.


Blocked coated pits in AtT20 cells result from endocytosis of budding retrovirions.
AtT20 cells support the replication of two endogenous retroviruses, a murine leukemia virus and a mouse mammary tumor virus. On glass or plastic substrates, AtT20 cells grow in clumps. In this situation, retroviruses budding from the plasma membrane of one cell can, on rare occasions, be invested by coated pits in the plasma membranes of contiguous cells. These pits can invaginate to depths of 2,000-4,000 A within the cytoplasm drawing with them the viral buds which remain connected to their parental cells by tubular stalks, some of which are only 225 +/- 15 A in diameter. These stalks run down the straight necks of the pits from the buds to the parental cell surfaces. Several lines of evidence indicate that these unique structures are blocked such that neither endocytosis nor budding can go to completion, and that they persist for several hours. The properties of these blocked coated pits are relevant to models of both endocytosis and viral budding. First, they indicate that the invagination of a coated pit is not absolutely dependent on its pinching off to form a coated vesicle, but that uncoating appears to be dependent upon the generation of a free vesicle. Secondly, they suggest that the final stages in the maturation of a retroviral core into a mature nucleoid are dependent on the detachment of the bud from its parental cell and that the driving force of budding is the association of viral transmembrane proteins with viral core proteins. An explanation is offered to account for the formation of these structures despite the phenomenon of viral interference.


Carers' perceptions of pain in people with dementia: a grounded theory approach.
The purpose of this Grounded Theory based study was to add to the limited understanding about the perception and observation of pain by the formal and informal carers of people with dementia. Thirty-one carers talked about how they know when their person with dementia has pain. Findings showed there is no one set of signs or behaviours that indicate pain in all people with dementia. However, a common pain assessment process amongst carers involved being able to detect deviation from normal behaviours based upon their intimate knowledge of what is normal for their person. A central hypothesis was thus generated from the data that considered that effective pain assessment for people with dementia is dependent on carers having an intimate knowledge of the individual's normal state of being with dementia. Implications for nursing practice are discussed.


Effect of temperature on life history of Cirrospilus vittatus (Hymenoptera: Eulophidae), an ectoparasitoid of Phyllocnistis citrella (Lepidoptera: Gracillariidae).
Cirrospilus vittatus is a generalist parasitoid detected on the invading Phyllocnistis citrella 1 yr after the introduction of this pest into Spain in 1993. In this study, the influence of temperature on parasitoid development, survival, and some selected life history parameters was determined. Development times shortened as the temperature increased from 15 to 30 degrees C, but increased between 30 and 35 degrees C. Larval development times varied the greatest over the range of temperatures, whereas egg development varied the least. The estimated upper and lower development thresholds were 38.2 and 8.2 degrees C, respectively, and the maximal developmental rate (8.75 d(-1)) occurred at 31.5 degrees C. The thermal constant was 275.1 +/- 4.6 degree-days. Cirrospilus vittatus appeared to be a synovigenic species. Mean fecundity at 25 degrees C was 39.17 eggs per female, and the oviposition rate fluctuated around five eggs per day. Superparasitism was quite common (42.8%), but fertility was high (85.6%). Immature C. vittatus survival was 58.1%. From these results, an intrinsic rate of increase of 0.126 females per female per day was estimated. Although under typical Mediterranean climatic conditions, development of C. vittatus could continue throughout the year, its reproductive fitness at 25 degrees C is lower than other leafminer parasitoids attacking P. citrella in Spain. These results could account for the progressive displacement observed in field populations occurring between C. vittatus and the predominant indigenous parasitoids of P. citrella, Cirrospilus sp. near lyncus.


Differential expression of extracellular proteins is correlated with angiogenesis in vitro.
Strains of bovine aortic endothelial cells, grown on plastic under conventional culture conditions and in the absence of growth factor supplementation, exhibited a sprouting phenotype and a predisposition toward the formation of cords and tubular structures. We examined endothelial cells at different stages of tube formation. Analysis of metabolically labeled proteins showed that the synthesis of type I collagen was initiated in sprouting cells and during the formation of tubular structures. SPARC (secreted protein, acidic and rich in cysteine) a Ca2(+)-binding protein associated with cellular shape change and morphogenetic processes (Sage H, Vernon RB, Funk SE, Everitt EA, Angello J: J Cell Biol 109:341, 1989), was upregulated during spontaneous tube formation. Levels of messenger RNA for type I collagen and SPARC corroborated the stage-specific increases observed for these proteins. Differential levels of transcription were apparent in multilayered cells directly involved in tube formation, in comparison with cells comprising either the tubes or the confluent monolayers at a distance from the tubes. Analysis of DNA synthesis indicated that multilayered sprouting cells in the proximity of the endothelial tubes were actively proliferating, whereas cells that had been incorporated into tubes showed low levels of DNA synthesis. Immunolabeling studies revealed a dense accumulation of SPARC and type I collagen in the cytoplasm of cells that were situated near the growing tubes. Two other secreted proteins, type III collagen and thrombospondin, were expressed constitutively by subconfluent cultures and were increased in those cells contributing to tube formation. We propose that type I collagen and SPARC are specifically related to the angiogenesis-like phenomenon displayed by bovine aortic endothelial cells in vitro. Type I collagen might facilitate the active migration of endothelial cells, or the stabilization of the resulting tubes, with SPARC directing the re-organization and dynamic assembly of the tubular network.


Catastrophic events and older adults.
The plight of older adults during catastrophic events is a societal concern. Older persons have an increased prevalence of cognitive disorders, chronic illnesses, and mobility problems that limit their ability to cope. These disorders may result in a lack of mental capacity and the ability to discern when they should evacuate or resolve problems encountered during a catastrophe. Some older persons may have limited transportation options, and many of the elderly survivors are at increased risk for abuse, neglect, and exploitation. Recommendations for future catastrophic events include the development of a federal tracking system for elders and other vulnerable adults, the designation of separate shelter areas for elders and other vulnerable adults, and involvement of gerontological professionals in all aspects of emergency preparedness and care delivery, including training of frontline workers. Preparation through preevent planning that includes region-specific social services, medical and public health resources, volunteers, and facilities for elders and vulnerable adults is critical. Elders need to be protected from abuse and fraud during catastrophic events. A public health triage system for elders and other vulnerable populations in pre- and postdisaster situations is useful, and disaster preparedness is paramount. Communities and members of safety and rescue teams must address ethical issues before an event. When older adults are involved, consideration needs to be given to triage decision making, transporting those who are immobile, the care of older adults who receive palliative care, and the equitable distribution of resources. Nurses are perfectly equipped with the skills, knowledge, and training needed to plan and implement disaster preparedness programs. In keeping with the tradition of Florence Nightingale, nurses can assume several crucial roles in disaster preparedness for older adults. Nurses possess the ability to participate and lead community policy development, serve on rescue teams, perform patient assessments, and deliver care. Nurses are crucial to well-planned and executed programs for catastrophic events that affect older adults. Also, all health care providers involved must be aware of the physical and psychological ramifications of disaster relief. The health and resilience of disaster-relief teams depend on paying attention to signs and symptoms of posttraumatic stress disorder and seeking appropriate treatment should it occur.


Approaches to Distal Upper-Extremity Trauma: A Comparison of Plastic, Orthopedic, and Hand Surgeons in Academic Practice.
Hand trauma call duties at university medical centers are traditionally split among plastic surgeons and orthopedic surgeons, frequently without additional fellowship training in hand and upper-extremity surgery. Differences in operative approach between these groups have never been specifically described. The University Health Consortium-Association of American Medical Colleges Faculty Practice Solutions Center database contains comprehensive, factual, billing and coding data from 90 academic medical centers in the United States and can be used to characterize the practice patterns of various academic surgical specialties. To characterize and compare the clinical experience of academic plastic, orthopedic, and hand surgeons in addressing traumatic distal upper extremity injuries (using the Faculty Practice Solutions Center data set). Annual data for CPT defined procedures related to traumatic injuries of the nail bed, finger, hand, wrist, and forearm performed by plastic, orthopedic, and hand surgeons during calendar years 2010 to 2013 were included in the study. From 2010 to 2013, the experience of fellowship-trained hand surgeons in treating traumatic distal upper extremity injuries was consistently greater than that of plastic surgeons and general orthopedic surgeons across all categories. Injuries of the nail bed were repaired more frequently by plastic surgeons than orthopedic surgeons (average 1.3 annual procedures per surgeon for plastic surgeons compared with 0.3 for orthopedic surgeons). Fractures and dislocations involving the phalanx and metacarpal were repaired equally by both groups, with plastic surgeons using predominantly percutaneous (38%) or open methods (45% of repairs), and orthopedic surgeons using mostly closed reduction (59% of repairs), splinting, and casting. Fractures and dislocations involving the carpal bones, radius, and ulna were more frequently repaired by orthopedic surgeons (average 23.2 procedures versus 2.6 for plastic surgeons), whereas tendon repairs in all segments were performed more frequently by plastic surgeons (average 13.7 procedures versus 2.5 for orthopedic surgeons). Replantation and repair of neurovascular injuries were exceedingly rare (less than 1 occurrence) in all groups for all years and are not specifically reported in Table 1. Similarly, incision and drainage procedures and decompressive fasciotomies of the distal upper extremity were uncommonly performed and also not included (Table 1 displays the mean annual procedures per surgeon by grouped CPT coded procedures, with overall averages displayed to the right. Figure 1 displays the proportions of intra-articular and extra-articular bony hand injuries treated by closed, open, and percutaneous methods by each specialty). A large degree of variation exists in the treatment of distal upper extremity injuries, based on specialty service. Hand surgeons, not surprisingly, have the most robust clinical experience, whereas plastic surgeons and orthopedic surgeons each display varying strengths and weaknesses, perhaps a consequence of their respective training.


Effects of Recombinant Human Bone Morphogenetic Protein-2 Dose and Ceramic Composition on New Bone Formation and Space Maintenance in a Canine Mandibular Ridge Saddle Defect Model.
Treatment of mandibular osseous defects is a significant clinical challenge. Maintenance of the height and width of the mandibular ridge is essential for placement of dental implants and restoration of normal dentition. While guided bone regeneration using protective membranes is an effective strategy for maintaining the anatomic contour of the ridge and promoting new bone formation, complications have been reported, including wound failure, seroma, and graft exposure leading to infection. In this study, we investigated injectable low-viscosity (LV) polyurethane/ceramic composites augmented with 100 μg/mL (low) or 400 μg/mL (high) recombinant human bone morphogenetic protein-2 (rhBMP-2) as space-maintaining bone grafts in a canine mandibular ridge saddle defect model. LV grafts were injected as a reactive paste that set in 5-10 min to form a solid porous composite with bulk modulus exceeding 1 MPa. We hypothesized that compression-resistant LV grafts would enhance new bone formation and maintain the anatomic contour of the mandibular ridge without the use of protective membranes. At the rhBMP-2 dose recommended for the absorbable collagen sponge carrier in dogs (400 μg/mL), LV grafts maintained the width and height of the host mandibular ridge and supported new bone formation, while at suboptimal (100 μg/mL) doses, the anatomic contour of the ridge was not maintained. These findings indicate that compression-resistant bone grafts with bulk moduli exceeding 1 MPa and rhBMP-2 doses comparable to that recommended for the collagen sponge carrier support new bone formation and maintain ridge height and width in mandibular ridge defects without protective membranes.


Genetic association of TCF4 intronic polymorphisms, CTG18.1 and rs17089887, with Fuchs' endothelial corneal dystrophy in an Indian population.
To assess the genetic association of transcription factor 4 (TCF4) intronic polymorphisms and CTG18.1 allele in individuals with Fuchs' endothelial corneal dystrophy (FECD) individuals from a sample Indian population. Forty-four FECD patients and 108 unrelated age-matched controls were recruited with informed consent for this study. Three, single nucleotide polymorphisms (SNPs) spanning the third intronic region of TCF4 (rs613872, rs17089887, and rs17089925) and an unstable trinucleotide repeat CTG18.1 allele were genotyped by direct sequencing using Sanger's method. The association of polymorphisms was analyzed using χ(2) test and logistic regression. SNP rs17089887 (P = 0.013) and CTG18.1 (P = 2 × 10(-4)) alleles were found to be significantly associated with FECD in the sample Indian population. However, the other two SNPs, rs613872 and rs17089925, were not likewise associated. Thirty-four percent of FECD subjects and 5% of control individuals harbor more than 50 trinucleotide repeats, which was considered as the disease threshold. TCF4 poses a major contributor to FECD manifestation globally, with a significant association of rs17089887 and CTG18.1 allele in the Indian population.


Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes.
In somatic cells, the heterodimeric Structural Maintenance of Chromosomes (SMC) proteins are involved in chromosome condensation and gene dosage compensation (SMC2 and 4), and sister chromatid cohesion and DNA recombination (SMC1 and 3). We report here evidence for an involvement of mammalian SMC1 and SMC3 proteins in meiosis. Immunofluorescence analysis of testis sections showed intense chromatin association in meiotic prophase cells, weaker staining in round spermatids and absence of the SMC proteins in elongated spermatids. In spermatocyte nuclei spreads, the SMC1 and SMC3 proteins localize in a beaded structure along the axial elements of synaptonemal complexes of pachytene and diplotene chromosomes. Both SMC proteins are present in rat spermatocytes and enriched in preparations of synaptonemal complexes. Several independent experimental approaches revealed interactions of the SMC proteins with synaptonemal complex-specific proteins SCP2 and SCP3. These results suggest a model for the arrangement of SMC proteins in mammalian meiotic chromatin.


Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes.
Monocytes play a critical role in defending the host against foreign organisms and in regulating the behavior of other cells. Monocytes circulate as nonadherent cells in the blood and migrate as adherent cells through tissues. Adhesion molecules mediate not only cell adhesion, but also migration, phagocytosis, and many other adhesion-dependent functions. Monocyte chemoattractant protein-1 (MCP-1) is thought to be responsible for monocyte recruitment in acute inflammatory conditions and may be an important mediator in chronic inflammation. In this study, immunofluorescence flow cytometry was used to determine whether MCP-1 can regulate the cell surface expression of adhesion molecules, particularly beta-2 and alpha-4 integrins and the leukocyte adhesion molecule-1. We found that MCP-1 induced expression of CD11c (p150,95 alpha-subunit) and CD11b (Mac-1 alpha-subunit), and caused little or no change of CD11a (lymphocyte function-associated Ag-1 alpha-subunit), very late activation Ag-4, or leukocyte adhesion molecule-1. We demonstrated that antibodies to beta-2 and alpha-4 integrins inhibited MCP-1-induced monocyte chemotaxis. We also showed that MCP-1 is capable of inducing IL-1 and IL-6, but not TNF production of monocytes. These results indicate that MCP-1 is not only a chemoattractant but also a novel cytokine with the capacity to regulate several parameters of monocyte function.


Comparison of the effect of multiple short-duration with single long-duration exercise sessions on glucose homeostasis in type 2 diabetes mellitus.
We evaluated and compared the effects on glycaemic control of two different exercise protocols in elderly men with type 2 diabetes mellitus. Eighteen patients with type 2 diabetes mellitus carried out home-based bicycle training for 5 weeks. Patients were randomly assigned to one of two training programmes at 60% of maximal oxygen uptake: three 10 min sessions per day (3 x 10) or one 30 min session per day (1 x 30). Plasma insulin, C-peptide and glucose concentrations were measured during a 3 h oral glucose tolerance test (OGTT). Insulin sensitivity index (ISI(composite)), pre-hepatic insulin secretion rates (ISR) and change in insulin secretion per unit change in glucose concentrations (B(total)) were calculated. Cardiorespiratory fitness increased in response to training in both groups. In group 3 x 10 (n = 9) fasting plasma glucose (p = 0.01), 120 min glucose OGTT (p = 0.04) and plasma glucose concentration areas under the curve at 120 min (p < 0.04) and 180 min (p = 0.07) decreased. These parameters remained unchanged in group 1 x 30 (n = 9). No significant changes were found in ISI(composite), ISR and B(total) in either of the exercise groups. In a matched time-control group (n = 10), glycaemic control did not change. Moderate to high-intensity training performed at 3 x 10 min/day is preferable to 1 x 30 min/day with regard to effects on glycaemic control. This is in spite of the fact that cardiorespiratory fitness increased similarly in both exercise groups. A possible explanation is that the energy expenditure associated with multiple short daily sessions may be greater than that in a single daily session.


Health Care Provider Communication and the Duration of Time Loss Among Injured Workers: A Prospective Cohort Study.
In addition to providing injured workers with biomedical treatment, health care providers (HCPs) can promote return to work (RTW) through various communications. To test the effect of several types of HCP communications on time loss following injury. The authors analyzed survey and administrative claims data from a total of 730 injured workers in Victoria, Australia. Survey responses were collected around 5 months postinjury and provided data on HCP communication and confounders. Administrative claim records provided data on compensated time loss postsurvey. The authors conducted multivariate zero-inflated Poisson regressions to determine both the odds of having future time loss and its duration. Types of HCP communications included providing an estimated RTW date, discussing types of activities the injured worker could do or ways to prevent a recurrence, and contacting other RTW stakeholders. Each was measured in isolation as well as modified by a low-stress experience with the HCP. Time loss was the count of cumulative compensated work absence in weeks, accrued postsurvey. RTW dates reduced the odds of future time loss [odds ratio, 0.26; 95% confidence interval (CI), 0.09-0.82] regardless of the stressfulness of the experience. Communications that predicted shorter durations of time loss only did so with low-stress experiences: RTW date [incidence rate ratio (IRR), 0.56; 95% CI, 0.50-0.63], stakeholder contact (IRR, 0.78; 95% CI, 0.70-0.87), and prevention discussions (IRR, 0.87; 95% CI, 0.78-0.98). HCPs may reduce time loss through several types of communication, particularly when stress is minimized. RTW dates had the largest and most robust effect.


Characterization of rodent models of HIV-gp120 and anti-retroviral-associated neuropathic pain.
A distal symmetrical sensory peripheral neuropathy is frequently observed in people living with Human Immunodeficiency Virus Type 1 (HIV-1). This neuropathy can be associated with viral infection alone, probably involving a role for the envelope glycoprotein gp120; or a drug-induced toxic neuropathy associated with the use of nucleoside analogue reverse transcriptase inhibitors as a component of highly active anti-retroviral therapy. In order to elucidate the mechanisms underlying drug-induced neuropathy in the context of HIV infection, we have characterized pathological events in the peripheral and central nervous system following systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) with or without the concomitant delivery of HIV-gp120 to the rat sciatic nerve (gp120+ddC). Systemic ddC treatment alone is associated with a persistent mechanical hypersensitivity (33% decrease in limb withdrawal threshold) that when combined with perineural HIV-gp120 is exacerbated (48% decrease in threshold) and both treatments result in thigmotactic (anxiety-like) behaviour. Immunohistochemical studies revealed little ddC-associated alteration in DRG phenotype, as compared with known changes following perineural HIV-gp120. However, the chemokine CCL2 is significantly expressed in the DRG of rats treated with perineural HIV-gp120 and/or ddC and there is a reduction in intraepidermal nerve fibre density, comparable to that seen in herpes zoster infection. Moreover, a spinal gliosis is apparent at times of peak behavioural sensitivity that is exacerbated in gp120+ddC as compared to either treatment alone. Treatment with the microglial inhibitor, minocycline, is associated with delayed onset of hypersensitivity to mechanical stimuli in the gp120+ddC model and reversal of some measures of thigmotaxis. Finally, the hypersensitivity to mechanical stimuli was sensitive to systemic treatment with gabapentin, morphine and the cannabinoid WIN 55,212-2, but not with amitriptyline. These data suggests that both neuropathic pain models display many features of HIV- and anti-retroviral-related peripheral neuropathy. They therefore merit further investigation for the elucidation of underlying mechanisms and may prove useful for preclinical assessment of drugs for the treatment of HIV-related peripheral neuropathic pain.


Instrument-free nucleic acid amplification assays for global health settings.
Many infectious diseases that affect global health are most accurately diagnosed through nucleic acid amplification and detection. However, existing nucleic acid amplification tests are too expensive and complex for most low-resource settings. The small numbers of centralized laboratories that exist in developing countries tend to be in urban areas and primarily cater to the affluent. In contrast, rural area health care facilities commonly have only basic equipment and health workers have limited training and little ability to maintain equipment and handle reagents.1 Reliable electric power is a common infrastructure shortfall. In this paper, we discuss a practical approach to the design and development of non-instrumented molecular diagnostic tests that exploit the benefits of isothermal amplification strategies. We identify modular instrument-free technologies for sample collection, sample preparation, amplification, heating, and detection. By appropriately selecting and integrating these instrument-free modules, we envision development of an easy to use, infrastructure independent diagnostic test that will enable increased use of highly accurate molecular diagnostics at the point of care in low-resource settings.


Vaginal fold histology reduces the variability introduced by vaginal exfoliative cytology in the classification of mouse estrous cycle stages.
Vaginal exfoliative cytology is commonly used in biomedical and toxicological research to classify the stages of the rodent estrous cycle. However, mouse vaginal exfoliative cytology is commonly used as a stand-alone tool and has not been evaluated in reference to vaginal histology and serum sex hormone levels. In this study, the direct and Giemsa-stained methods of vaginal exfoliative cytology were compared in reference to vaginal fold histology and serum sex hormone levels. Both methods predicted the estrous stages similarly with mean discordance rates of 55%, 77%, 46%, and 31%, for diestrus, proestrus, estrus, and metestrus, respectively. From these results, we conclude that vaginal exfoliative cytology may be used as a general guide to determine the desired estrous stage end point and that a definitive confirmation of the estrous stage should be obtained from evaluation of vaginal fold histology. Confirmation of the stage of the estrous cycle by vaginal fold histology will decrease the variability otherwise introduced by misclassification of estrous cycle stages with vaginal exfoliative cytology.


Melanesian prehistory: some recent advances.
Human occupation of New Guinea had begun 50,000 years ago, but islands further east were settled only in Recent times. In part of the New Guinea highlands, wet and dry horticultural systems began by 9000 years ago. Local intensification is evident until the present, but only the most recent major crop (sweet potato, which has been grown in the region for less than 300 years) is documented. On the south coast, exchange systems and economies locally diversify over the last two millennia. In the Melanesian islands, exotic materials were moved 3000 kilometers 3000 years ago, but whether traders or colonists were involved is not yet clear. The prehistory of the area is proving more complex than was believed even a decade ago.


Dysglycemia and long-term mortality: observations from the Israel study of glucose intolerance, obesity and hypertension.
We describe the relationship between dysglycemia and long-term mortality and elucidate the relationship between blood glucose levels during an oral glucose tolerance test (OGTT) and haemoglobin A1 (HbA1) and mortality. A cohort of 1410 individuals was followed for 33 years since 1980. Fasting and post-OGTT glucose parameters were used to categorize the cohort according to baseline glycemic status. The mortality rate increased from 43% in normoglycemic individuals to 53.3, 61.7, 72.9 and 88.0% in those with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and diabetes, respectively. The highest mortality rate, compared with the normoglycemic category, was observed in individuals with IFG/IGT and diabetes according to a Cox proportional hazard model (HR = 1.38, 95%CI 1.10-1.74 and HR = 2.14, 95%CI 1.70-2.70, respectively), followed by individuals with IGT and IFG, but this did not reach statistical significance. We speculate that the IFG group may represent a mixture of individuals en route from normal to the next two categories as well as another cohort whose glucose levels are stably set at the upper reaches of the normal distribution. Significant differences were found between 1 and 2 h glucose values (p < 0.001). Fasting, 60 and 120 min glucose values were positively associated with increasing HbA1 quintiles (p < 0.05). The mean HbA1 was significantly higher in those who died (p = 0.01). The highest mortality (58.8%) was observed in the upper HbA1 quintile that was also associated with the highest prevalence of the metabolic syndrome (17.2%). This study shows a continuous relationship between the severity of dysglycemia and long-term mortality and should promote the early recognition of prediabetes. The 1 h post-load glucose level was continuously associated with increasing HbA1 concentrations and may therefore serve as an early marker for abnormalities in glucose tolerance. An elevated 1 h post-load glucose level may potentially identify at-risk individuals well before the traditional 2 h glucose value.


Paget's disease: improvement of spinal cord dysfunction with diphosphonates and calcitonin.
The clinical and radiographic features of spinal cord dysfunction secondary to Paget's disease are described. Long-term medical management with the use of the diphosphonates, calcitonins and mithramycin resulted in marked and rapid clinical improvements in 8 of 10 of our own patients. These results are comparable to those seen in 19 other patients previously described in the literature, and are also similar to those obtained by surgical treatment. The recurrence rate and mortality (approximately 10%) of surgical treatment suggest that drug treatment now has a place in the management of paraparesis, particularly when this is of gradual onset. Medical management may also provide a valuable adjunct in those cases where surgery is required (e.g. sudden onset of paraparesis). In patients with cord dysfunction, but without significant anatomical compression of the spinal cord, it is suggested that paraparesis may be caused by a "vascular steal" syndrome, a notion which is supported by the rapidity with which drug-induced remission occurs.


Statistical mechanics of letters in words.
We consider words as a network of interacting letters, and approximate the probability distribution of states taken on by this network. Despite the intuition that the rules of English spelling are highly combinatorial and arbitrary, we find that maximum entropy models consistent with pairwise correlations among letters provide a surprisingly good approximation to the full statistics of words, capturing ∼92% of the multi-information in four-letter words and even "discovering" words that were not represented in the data. These maximum entropy models incorporate letter interactions through a set of pairwise potentials and thus define an energy landscape on the space of possible words. Guided by the large letter redundancy we seek a lower-dimensional encoding of the letter distribution and show that distinctions between local minima in the landscape account for ∼68% of the four-letter entropy. We suggest that these states provide an effective vocabulary which is matched to the frequency of word use and much smaller than the full lexicon.


The validity of teens' and young adults' self-reported condom use.
To examine the concordance between teens' and young adults' self-reported condom use, assessed by audio-computer-assisted self-interviewing, and Y-chromosome polymerase chain reaction (Yc-PCR) assay, a nondisease marker for detecting the presence of sperm in vaginal fluid for 14 days after unprotected vaginal sex. Randomized trial of a human immunodeficiency virus prevention program. Only data from baseline (before randomization) were used for this analysis. A clinic-based sample in Atlanta, Georgia. Eligible teens and young adults were African American female teens and young adults 15 to 21 years old who had reported sexual activity in the previous 60 days. Of 1558 teens and young adults screened from March 1, 2002, through August 31, 2004, 847 were eligible and 715 (84.4%) participated at baseline. Self-reported consistent condom use in the 14 days before baseline and Yc-PCR results. Of participants who reported vaginal sex in the past 14 days, 186 reported consistent condom use, defined as 100% condom use. Of these, 63 had a positive Yc-PCR result, indicating detection of the Y chromosome in the vaginal fluid. Participants who reported consistent condom use with a self-reported history of sexually transmitted diseases were 2.4 times more likely to have a positive Yc-PCR result (adjusted odds ratio, 2.4; 95% confidence interval, 1.2-4.8; P = .01). A significant degree of discordance between self-reports of consistent condom use and Yc-PCR positivity was observed. Several rival explanations for the observed discordance exist, including (1) teens and young adults inaccurately reported condom use; (2) teens and young adults used condoms consistently but used them incorrectly, resulting in user error; and (3) teens and young adults responded with socially desirable answers. Using an objective biological measure may provide one strategy for validating teens' and young adults' self-reported condom use.


Legitimating the illegitimate: How doctors manage their knowledge of the prestige of diseases.
Although the sociology of medicine has developed a rich body of research on patients' experiences and how they handle their illnesses, few analyses have examined doctors' concepts of disease. Building on previous research findings that doctors consider some diseases to be more worthy than others, this article focuses on how these differences in disease prestige are articulated and made logical. We presented a focus group panel of doctors a table of 38 diseases rank-ordered by prestige according to the results of a previous quantitative study of doctors. We prompted a lively discussion among the doctors by asking them whether they were familiar with this rank order. In analysing how they managed the prestige knowledge presented to them, we focused on how they handled the value conflict between this informal rank order and the formal value of equality of treatment. Using positioning theory as a theoretical premise and a methodological tool, we found that the focus group participants created positions in their conversations that allowed them to present and discuss views on disease prestige that would be considered illegitimate if they were declared directly. However, they were able to do so without being forced to take a personal stand. Thus, we demonstrate how informal disease rankings can be produced and reproduced.


A low-interaction automatic 3D liver segmentation method using computed tomography for selective internal radiation therapy.
This study introduces a novel liver segmentation approach for estimating anatomic liver volumes towards selective internal radiation treatment (SIRT). The algorithm requires minimal human interaction since the initialization process to segment the entire liver in 3D relied on a single computed tomography (CT) slice. The algorithm integrates a localized contouring algorithm with a modified k-means method. The modified k-means segments each slice into five distinct regions belonging to different structures. The liver region is further segmented using localized contouring. The novelty of the algorithm is in the design of the initialization masks for region contouring to minimize human intervention. Intensity based region growing together with novel volume of interest (VOI) based corrections is used to accomplish the single slice initialization. The performance of the algorithm is evaluated using 34 liver CT scans. Statistical experiments were performed to determine consistency of segmentation and to assess user dependency on the initialization process. Volume estimations are compared to the manual gold standard. Results show an average accuracy of 97.22% for volumetric calculation with an average Dice coefficient of 0.92. Statistical tests show that the algorithm is highly consistent (P = 0.55) and independent of user initialization (P = 0.20 and Fleiss' Kappa = 0.77 ± 0.06).


Effects of spatial and temporal resolution for MR image-guided thermal ablation of prostate with transurethral ultrasound.
To describe approaches for determining optimal spatial and temporal resolutions for the proton resonance frequency shift method of quantitative magnetic resonance temperature imaging (MRTI) guidance of transurethral ultrasonic prostate ablation. Temperature distributions of two transurethral ultrasound applicators (90 degrees sectored tubular and planar arrays) for canine prostate ablation were measured via MRTI during in vivo sonication, and agree well with two-dimensional finite difference model simulations at various spatial resolutions. Measured temperature distributions establish the relevant signal-to-noise ratio (SNR) range for thermometry in an interventional MR scanner, and are reconstructed at different resolutions to compare resultant temperature measurements. Various temporal resolutions are calculated by averaging MRTI frames. When noise is added to simulated temperature distributions for tubular and planar applicators, the minimum root mean squared (RMS) error is achieved by reconstructing to pixel sizes of 1.9 and 1.7 mm, respectively. In in vivo measurements, low spatial resolution MRTI data are shown to reduce the noise without significantly affecting thermal dose calculations. Temporal resolution of 0.66 frames/minute leads to measurement errors of more than 12 degrees C during rapid heating. Optimizing MRTI pixel size entails balancing large pixel SNR gain with accuracy in representing underlying temperature distributions.


Quantifying Vulnerability to Extreme Heat in Time Series Analyses: A Novel Approach Applied to Neighborhood Social Disparities under Climate Change.
We propose a novel approach to examine vulnerability in the relationship between heat and years of life lost and apply to neighborhood social disparities in Montreal and Paris. We used historical data from the summers of 1990 through 2007 for Montreal and from 2004 through 2009 for Paris to estimate daily years of life lost social disparities (DYLLD), summarizing social inequalities across groups. We used Generalized Linear Models to separately estimate relative risks (RR) for DYLLD in association with daily mean temperatures in both cities. We used 30 climate scenarios of daily mean temperature to estimate future temperature distributions (2021-2050). We performed random effect meta-analyses to assess the impact of climate change by climate scenario for each city and compared the impact of climate change for the two cities using a meta-regression analysis. We show that an increase in ambient temperature leads to an increase in social disparities in daily years of life lost. The impact of climate change on DYLLD attributable to temperature was of 2.06 (95% CI: 1.90, 2.25) in Montreal and 1.77 (95% CI: 1.61, 1.94) in Paris. The city explained a difference of 0.31 (95% CI: 0.14, 0.49) on the impact of climate change. We propose a new analytical approach for estimating vulnerability in the relationship between heat and health. Our results suggest that in Paris and Montreal, health disparities related to heat impacts exist today and will increase in the future.


Average intensity and contrast of light amplified by a partially homogeneously broadened, slightly saturated laser amplifier with stochastic gain distributions.
We evaluate the average intensity and contrast of the output of a laser amplifier in which stochastic gain distributions exist. This situation occurs when turbulence flows are developed in a gas- or liquid-laser amplifier. The gain medium is assumed to be partially homogeneously broadened and slightly saturated and to consist of two-level atoms. In our computations, a plane wave is propagated through the gain medium with weak turbulences, under the assumption that the size of the first Fresnel zone is much smaller than the characteristic length of turbulences.


Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags.
Liver cancer is one of the leading causes of cancer death worldwide. To identify novel target genes that are related to liver carcinogenesis, we examined new genes that are differentially expressed in human hepatocellular carcinoma (HCC) cell lines and tissues based on the expressed sequence tag (EST) frequency. Eleven libraries were constructed from seven HCC cell lines and three normal liver tissue samples obtained from Korean patients. An analysis of gene expression profiles for HCC was performed using the frequency of ESTs obtained from these cDNA libraries. Genes were identified (n=120) as being either up- or down-regulated in human liver cancer cells. Among these, 14 genes (FTL, K-ALPHA1, LDHA, RPL4, ENO1, ANXA2, RPL9, RPL10, RPL13A, GNB2L1, AMBP, GC, A1BG, and SERPINC1), in addition to previously well-known liver cancer related genes, were confirmed to be differentially expressed in seven liver cancer cell lines and 17 HCC tissues by semi-quantitative RT-PCR. In addition, 73 genes, in which there was a significant difference (P>0.99) between HBV- and HCV-associated HCC cells, were selected. Of these, expression patterns of 14 (RPLP0, AKR1C, KRT8, GPX4, RPS15, ID1, RPS21, VIM, EEF1G, EIF4A1, HLA-C, FN1, CD44, and RPS10) were confirmed by semi-quantitative RT-PCR in four of HBV- and three of HCV-associated HCC cell lines. Among those genes, an immunohistochemical analysis for ANXA2 showed that it is expressed at high levels in HCC. Using an analysis of EST frequency, the newly identified genes, especially ANXA2, represent potential biomarkers for HCC and useful targets for elucidating the molecular mechanisms associated with HCC involving virological etiology.


A cross-sectional study on levels of second-hand smoke in restaurants and bars in five cities in China.
To assess indoor second-hand smoke (SHS) exposure in restaurants and bars via PM(2.5) (fine particles 2.5 μm in diameter and smaller) level measurements in five cities in China. The study was conducted from July to September in 2007 in Beijing, Xi'an, Wuhan, Kunming and Guiyang. Portable aerosol monitors were used to measure PM(2.5) concentrations in 404 restaurants and bars. The occupant density and the active smoker density were calculated for each venue sampled. Among the 404 surveyed venues, 23 had complete smoking bans, 9 had partial smoking bans and 313 (77.5%) were observed to have allowed smoking during sampling. The geometric mean of indoor PM(2.5) levels in venues with smoking observed was 208 μg/m(3) and 99 μg/m(3) in venues without observed smoking. When outdoor PM(2.5) levels were adjusted, indoor PM(2.5) levels in venues with smoking observed were consistently significantly higher than in venues without smoking observed (F=80.49, p<0.001). Indoor PM(2.5) levels were positively correlated with outdoor PM(2.5) levels (partial rho=0.37 p<0.001) and active smoker density (partial rho=0.34, p<0.001). Consistent with findings in other countries, PM(2.5) levels in smoking places are significantly higher than those in smoke-free places and are strongly related to the number and density of active smokers. These findings document the high levels of SHS in hospitality venues in China and point to the urgent need for comprehensive smoke-free laws in China to protect the public from SHS hazards, as called for in Article 8 of the Framework Convention on Tobacco Control, which was ratified by China in 2005.


A Systematic Review of Outcome Measures Assessing Disability Following Upper Extremity Trauma.
To define upper extremity outcome measures focusing on trauma and level of initial psychometric evaluation and to assess methodological quality of relevant patient-reported outcome (PRO) measures. A broad search strategy using PubMed, OVID, CINAHL, and PsycINFO was deployed and reported using PRISMA (PROSPERO: CRD42016046243). PRO measures involving orthopedic trauma in their original development were selected and original publications assessed, including psychometric evaluations. Extraction, synthesis, and quality assessment were performed using COSMIN. Of 144 upper extremity outcome measures, the majority were designed for the shoulder, wrist, and hand; 20% (n = 29/144) involved trauma conditions in their initial development, PRO measurements, and psychometric evaluation on introduction. Methodological quality was highly variable. A few PRO measures were originally designed for use in upper extremity trauma. Methodological quality and psychometric evaluation need to improve. This review aims to highlight strengths and weaknesses and guide decision making in this field.


A steady-state approach of benefit-cost analysis with a periodic leslie-matrix model. Presentation and application to the evaluation of a sheep-diseases preventive scheme in Kolda, Senegal.
A seasonal population-dynamics matrix model (periodic Leslie-matrix model) was developed to model short production cycles and high seasonal variations occurring in demographic rates and offtake patterns for small ruminants. The year was split into 24- and 15-day phases. Population-size changes were modelled by the recurrence equation x(j+1)=B(j)x(j), where j was the 15-day phase, x an age-class population size vector and B a fecundity-, mortality-, offtake- and intake-rate matrix. Given an initial vector x(1), annual dynamics were described by x(25)=B(24)...B(1)x(1)=Ax(1), where A was the annual projection matrix.A steady-state hypothesis was used to estimate offtake gains and financial returns from a trial of pasteurellosis vaccination and anthelminthic drench in traditionally managed sheep flocks in Senegal, from July 1987 to June 1988. Nineteen villages and 76 herds were involved in the experiment. Villages were randomly allocated to one of the four treatment combinations in a factorial design, and subsequent demographic rates and net offtake patterns were measured. In the trial, vaccination had a negative effect on offtakes among females. No vaccination effect was observed for males. A positive effect of deworming was found for both sexes. From the trial data, our model calculated that the overall ratio of offtakes (i.e. number of animals) for dewormed over undrenched sheep was 1.2 (95% confidence interval: 1.1, 1.4). The deworming financial benefit-cost ratio was 3.7 (1.9, 5.4).


[DSM-5 classification of personality disorders in older persons].
Although it is generally agreed that personality disorders are an important topic in old-age psychiatry, DSM-5 has paid relatively little attention to older persons affected with this severe mental disorder. To look closely and carefully at several aspects of the way in which DSM-5 defines personality disorders relating to older persons. We make a critical evaluation of the description of personality disorders given in DSM-5. First of all, we question whether the phrase 'personality change due to another medical condition' should really be included in the dsm-5 chapter of personality disorders because a personality change actually has the features of a persistent conduct disorder. Secondly, we argue that in a future revised version of dsm-5 personality disorders affecting older persons should be referred to specifically as 'late-onset' personality disorders. Thirdly, we stress that the research programme relating to the dimensional dsm-5 model of personality disorders should involve a larger number of older persons. In addition, more research is needed with regard to the use, wording and validity of the phrase 'personality change due to a medical condition'. Those responsible for the revision of the DSM-5 should ensure that the concept 'late-onset personality disorders' is incorporated in the text. The description of personality disorders in DSM-5 is confusing. This is probably due to the transitional period between the old categorical (dsm-iv) system and the newly proposed dimensional approach to personality disorders in DSM-5, an approach that needs further investigation. However, this intervening period could be a good opportunity for doing further research into personality disorders in older adults.


Suppression of melatonin secretion in healthy subjects with eyeglass LED delivery system.
Practicability remains a problem in light therapy of biological rhythm disorders. We report here the effect on melatonin secretion of a device consisting of a prototype of eyeglasses including light emitting diodes (LED) in lenses (Somnavue). Light (1,200 lx) was administered in a randomised crossover design to ten healthy subjects with Somnavue for 1 or 2 hours, Lumino (a helmet which administers light) for 1 hour, and placebo, beginning at 01:00 h. Plasma melatonin concentrations were evaluated between 20:00-05:00 h. Multiple comparisons showed differences between placebo and Somnavue administered for one or two hours (p<0.01 and p<0.05 respectively) and Lumino and placebo (p<0.05). In conclusion, Somnavue was able to suppress melatonin. The development of such a device could increase adherence with light treatment in SAD or circadian rhythm sleep disorders.


Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect.
The regulation of HSC proliferation and engraftment of the BM is an important but poorly understood process, particularly during ontogeny. Here we show that in mice, all HSCs are cycling until 3 weeks after birth. Then, within 1 week, most became quiescent. Prior to 4 weeks of age, the proliferating HSCs with long-term multilineage repopulating activity displayed an engraftment defect when transiting S/G2/M. During these cell cycle phases, their expression of CXC chemokine ligand 12 (CXCL12; also referred to as stromal cell-derived factor 1 [SDF-1]) transiently increased. The defective engrafting activity of HSCs in S/G2/M was reversed when cells were allowed to progress into G1 prior to injection or when the hosts (but not the cells) were pretreated with a CXCL12 antagonist. Interestingly, the enhancing effect of CXCL12 antagonist pretreatment was exclusive to transplants of long-term multilineage repopulating HSCs in S/G2/M. These results demonstrate what we believe to be a new HSC regulatory checkpoint during development. They also suggest an ability of HSCs to express CXCL12 in a fashion that changes with cell cycle progression and is associated with a defective engraftment that can be overcome by in vivo administration of a CXCL12 antagonist.


Plaquing procedure for infectious hematopoietic necrosis virus.
A single overlay plaque assay was designed and evaluated for infectious hematopoietic necrosis virus. Epithelioma papillosum carpio cells were grown in normal atmosphere with tris(hydroxymethyl)aminomethane- or HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid)-buffered media. Plaques were larger and formed more quickly on 1- to 3-day-old cell monolayers than on older monolayers. Cell culture medium with a 10% addition of fetal calf serum (MEM 10) or without serum (MEM 0) were the most efficient virus diluents. Dilution with phosphate-buffered saline, saline, normal broth, or deionized water reduced plaque numbers. Variations in the pH (7.0 to 8.0) of a MEM 0 diluent did not affect plaque numbers. Increasing the volume of viral inoculum above 0.15 ml (15- by 60-mm plate) decreased plaquing efficiency. Significantly more plaques occurred under gum tragacanth and methylcellulose than under agar or agarose overlays. Varying the pH (6.8 to 7.4) of methylcellulose overlays did not significantly change plaque numbers. More plaques formed under the thicker overlays of both methylcellulose and gum tragacanth. Tris(hydroxymethyl)aminomethane and HEPES performed equally well, buffering either medium or overlay. Plaque numbers were reduced when cells were rinsed after virus adsorption or less than 1 h was allowed for adsorption. Variation in adsorption time between 60 and 180 min did not change plaque numbers. The mean plaque formation time was 7 days at 16 degrees C. The viral dose response was linear when the standardized assay was used.


Synergism between melatonin and atorvastatin against endothelial cell damage induced by lipopolysaccharide.
The beneficial effects of atorvastatin are based on both cholesterol-dependent and independent mechanisms. The latter probably include the ability of the estatin to enhance the expression of endothelial nitric oxide synthase (eNOS) and to cause a vasodilatation. In turn, the antioxidant and anti-inflammatory actions of melatonin are related to its vascular protection. In the present study, we investigated the efficacy of the combination of melatonin plus atorvastatin against endothelial cell damage induced by inflammation and oxidative stress injury. Human umbilical vein endothelial cells (HUVEC) were cultured with bacterial lipopolysaccharide (LPS) in the presence or absence of melatonin and/or atorvastatin. LPS inhibited eNOS mRNA and protein expression, which was reversed by atorvastatin and, to a lesser extent, by melatonin. Together, melatonin + atorvastatin induced higher eNOS protein expression than either compound alone. Melatonin, but not atorvastatin, reduced free radical generation, lipid peroxidation, and interleukin-6 levels induced by LPS. In the presence of atorvastatin, the effects of melatonin were maintained or even improved. These data suggest that melatonin improves the beneficial effects of atorvastatin and reduces its side effects in endothelial cells during inflammation and under conditions of oxidative stress.


Testing in serum for human glandular kallikrein 2, and free and total prostate specific antigen in biannual screening for prostate cancer.
We investigated the value of serum measurements for glandular kallikrein 2 (hK2), and free (f) and total (t) prostate specific antigen (PSA) in a second round of biannual screening for prostate cancer. In 1995 to 1996, 5,853 of 9,811 randomly selected men in Göteborg, Sweden 50 to 66 years old had PSA measurements. Of 660 men 611 with tPSA 3 ng/ml or greater underwent biopsy and 145 had cancer. All were re-invited 2 years later for PSA testing, and 506 of 596 men with tPSA 3 ng/ml or greater underwent biopsy and 113 cancers were detected. We analyzed hK2, tPSA and fPSA in 423 of 453 (93%) men who underwent biopsy in 1997 to 1998 who were also screened in 1995 to 1996. The 99 of 423 (23%) men who underwent biopsy diagnosed with prostate cancer in 1997 to 1998 had significantly different tPSA, percent fPSA and hK2 x tPSA/fPSA compared to the men with negative biopsies from 2 years earlier. The largest area under curve was obtained for hK2 x tPSA/fPSA in serum from 1995 to 1996 and from 1997 to 1998, but the difference was not significant compared to tPSA and percent fPSA. In serum from 1997 to 1998 measurements of hK2 x tPSA/fPSA gave significantly higher specificity than tPSA at 85% sensitivity, and significantly higher specificity than tPSA and percent fPSA at 70% to 75% sensitivity. In addition, levels of hK2 and hK2 x tPSA/fPSA manifested a significantly greater 2-year increase in men with cancer compared to those with benign biopsies. In men with tPSA levels 3.0 ng/ml or greater who were not diagnosed with cancer during a first round of screening, hK2 measurements enhanced specificity compared to tPSA testing at moderately high sensitivity, and manifested a greater 2-year increase in men with cancer.


Effect of Electronic Health Record-Based Medication Support and Nurse-Led Medication Therapy Management on Hypertension and Medication Self-management: A Randomized Clinical Trial.
Complex medication regimens pose self-management challenges, particularly among populations with low levels of health literacy. To test medication management tools delivered through a commercial electronic health record (EHR) with and without a nurse-led education intervention. This 3-group cluster randomized clinical trial was performed in community health centers in Chicago, Illinois. Participants included 794 patients with hypertension who self-reported using 3 or more medications concurrently (for any purpose). Data were collected from April 30, 2012, through February 29, 2016, and analyzed by intention to treat. Clinics were randomly assigned to to groups: electronic health record-based medication management tools (medication review sheets at visit check-in, lay medication information sheets printed after visits; EHR-alone group), EHR-based tools plus nurse-led medication management support (EHR plus education group), or usual care. Outcomes at 12 months included systolic blood pressure (primary outcome), medication reconciliation, knowledge of drug indications, understanding of medication instructions and dosing, and self-reported medication adherence. Medication outcomes were assessed for all hypertension prescriptions, all prescriptions to treat chronic disease, and all medications. Among the 794 participants (68.6% women; mean [SD] age, 52.7 [9.6] years), systolic blood pressure at 12 months was greater in the EHR-alone group compared with the usual care group by 3.6 mm Hg (95% CI, 0.3 to 6.9 mm Hg). Systolic blood pressure in the EHR plus education group was not significantly lower compared with the usual care group (difference, -2.0 mm Hg; 95% CI, -5.2 to 1.3 mm Hg) but was lower compared with the EHR-alone group (-5.6 mm Hg; 95% CI, -8.8 to -2.4 mm Hg). At 12 months, hypertension medication reconciliation was improved in the EHR-alone group (adjusted odds ratio [OR], 1.8; 95% CI, 1.1 to 2.9) and the EHR plus education group (adjusted odds ratio [OR], 2.0; 95% CI, 1.3 to 3.3) compared with usual care. Understanding of medication instructions and dosing was greater in the EHR plus education group than the usual care group for hypertension medications (OR, 2.3; 95% CI, 1.1 to 4.8) and all medications combined (OR, 1.7; 95% CI, 1.0 to 2.8). Compared with usual care, the EHR tools alone and EHR plus education interventions did not improve hypertension medication adherence (OR, 0.9; 95% CI, 0.6-1.4 for both) or knowledge of chronic drug indications (OR for EHR tools alone, 1.0 [95% CI, 0.6 to 1.5] and OR for EHR plus education, 1.1 [95% CI, 0.7-1.7]). The study found that EHR tools in isolation improved medication reconciliation but worsened blood pressure. Combining these tools with nurse-led support suggested improved understanding of medication instructions and dosing but did not lower blood pressure compared with usual care. ClinicalTrials.gov identifier: NCT01578577.


Adoptive T cell immunotherapy for cancer.
Harnessing the immune system to recognize and destroy tumor cells has been the central goal of anti-cancer immunotherapy. In recent years, there has been an increased interest in optimizing this technology in order to make it a clinically feasible treatment. One of the main treatment modalities within cancer immunotherapy has been adoptive T cell therapy (ACT). Using this approach, tumor-specific cytotoxic T cells are infused into cancer patients with the goal of recognizing, targeting, and destroying tumor cells. In the current review, we revisit some of the major successes of ACT, the major hurdles that have been overcome to optimize ACT, the remaining challenges, and future approaches to make ACT widely available.


Physical fitness and mental health impact of a sport-for-development intervention in a post-conflict setting: randomised controlled trial nested within an observational study of adolescents in Gulu, Uganda.
Physical inactivity contributes to poor fitness and mental health disorders. This is of concern in post-conflict low-income settings where non-communicable diseases are emerging and there is limited evidence for physical activity interventions. We examined the effects of a sport-for-development programme on adolescent physical fitness and mental health in Gulu, Uganda. We conducted a single-blinded RCT nested within an observational study with three unbalanced parallel groups. Participants were able-bodied adolescents aged 11-14 years. The intervention comprised an 11-week voluntary competitive sport-for-development football league. Participants who did not subscribe for the intervention formed a non-registered comparison group. Boys who registered for the sport-for-development programme were randomly allocated to the intervention or wait-listed. The girls programme subscription was insufficient to form a wait-list and all registrants received the intervention. Physical fitness was assessed by cardiorespiratory fitness (multi-stage fitness test), muscular power (standing broad jump) and body composition (BMI-for-age). Mental health was measured using the Acholi Psychosocial Assessment Instrument for local depression-like (DLS) and anxiety-like (ALS) syndromes. All randomisation was computer generated and assessors were masked to group allocation. An intention-to-treat analysis of adjusted effect size (ES) was applied. There were 1,462 adolescents in the study (intervention: boys = 74, girls = 81; wait-list: boys = 72; comparison: boys = 472, girls = 763). At four months follow-up there was no significant effect on the boys fitness when comparing intervention vs wait-listed and intervention vs non-registered groups. However, there was a negative effect on DLS when comparing boys intervention vs wait-listed (ES = 0.67 [0.33 to 1.00]) and intervention vs non-registered (ES = 0.25 [0.00 to 0.49]). Similar results were observed for ALS for boys intervention vs wait-listed (ES = 0.63 [0.30 to 0.96]) and intervention vs non-registered (ES = 0.26 [0.01 to 0.50]). There was no significant effect on the girls for any outcomes. The sport-for-development league in this study had no impact on fitness and a negative effect on the mental health of participating boys. From this research, there is no evidence that voluntary competitive sport-for-development interventions improve physical fitness or mental health outcomes in post-conflict settings.


Robust fast direct integral equation solver for quasi-periodic scattering problems with a large number of layers.
We present a new boundary integral formulation for time-harmonic wave diffraction from two-dimensional structures with many layers of arbitrary periodic shape, such as multilayer dielectric gratings in TM polarization. Our scheme is robust at all scattering parameters, unlike the conventional quasi-periodic Green's function method which fails whenever any of the layers approaches a Wood anomaly. We achieve this by a decomposition into near- and far-field contributions. The former uses the free-space Green's function in a second-kind integral equation on one period of the material interfaces and their immediate left and right neighbors; the latter uses proxy point sources and small least-squares solves (Schur complements) to represent the remaining contribution from distant copies. By using high-order discretization on interfaces (including those with corners), the number of unknowns per layer is kept small. We achieve overall linear complexity in the number of layers, by direct solution of the resulting block tridiagonal system. For device characterization we present an efficient method to sweep over multiple incident angles, and show a 25× speedup over solving each angle independently. We solve the scattering from a 1000-layer structure with 3 × 105 unknowns to 9-digit accuracy in 2.5 minutes on a desktop workstation.


The value of avian genomics to the conservation of wildlife.
Genomic studies in non-domestic avian models, such as the California condor and white-throated sparrow, can lead to more comprehensive conservation plans and provide clues for understanding mechanisms affecting genetic variation, adaptation and evolution.Developing genomic tools and resources including genomic libraries and a genetic map of the California condor is a prerequisite for identification of candidate loci for a heritable embryonic lethal condition. The white-throated sparrow exhibits a stable genetic polymorphism (i.e. chromosomal rearrangements) associated with variation in morphology, physiology, and behavior (e.g., aggression, social behavior, sexual behavior, parental care).In this paper we outline the utility of these species as well as report on recent advances in the study of their genomes. Genotyping of the condor resource population at 17 microsatellite loci provided a better assessment of the current population's genetic variation. Specific New World vulture repeats were found in the condor genome. Using condor BAC library and clones, chicken-condor comparative maps were generated. A condor fibroblast cell line transcriptome was characterized using the 454 sequencing technology.Our karyotypic analyses of the sparrow in combination with other studies indicate that the rearrangements in both chromosomes 2m and 3a are complex and likely involve multiple inversions, interchromosomal linkage, and pleiotropy. At least a portion of the rearrangement in chromosome 2m existed in the common ancestor of the four North American species of Zonotrichia, but not in the one South American species, and that the 2m form, originally thought to be the derived condition, might actually be the ancestral one. Mining and characterization of candidate loci in the California condor using molecular genetic and genomic techniques as well as linkage and comparative genomic mapping will eventually enable the identification of carriers of the chondrodystrophy allele, resulting in improved genetic management of this disease.In the white-throated sparrow, genomic studies, combined with ecological data, will help elucidate the basis of genic selection in a natural population. Morphs of the sparrow provide us with a unique opportunity to study intraspecific genomic differences, which have resulted from two separate yet linked evolutionary trajectories. Such results can transform our understanding of evolutionary and conservation biology.


Midlife Marital Dissolution and the Onset of Cognitive Impairment.
Marital dissolution has become more common in midlife with the doubling of the divorce rate among middle-aged adults. Guided by the stress model that stipulates losing economic, social, and psychological resources lowers well-being, we posited that midlife adults who experienced divorce or widowhood were at greater risk of cognitive impairment than the continuously married. Subsequent repartnering was expected to negate the increased risk. We used data from the 1998-2016 Health and Retirement Study to estimate discrete-time event history models using logistic regression to predict cognitive impairment onset for men and women. Roughly 27% of men who experienced spousal death in midlife went on to experience mild cognitive impairment by age 65. For women, experiencing divorce or widowhood was associated with higher odds of cognitive impairment onset although these differentials were accounted for by economic, social, and psychological resources. Men and women who repartnered after marital dissolution did not appreciably differ from their continuously married counterparts in terms of their likelihoods of cognitive impairment onset. A stressful life event, midlife marital dissolution can be detrimental to cognitive well-being, placing individuals at increased risk of developing dementia in later life. The growing diversity of partnership experiences during the second half of life points to the continued importance of examining how union dissolution and formation shape health and well-being.