Methodological issues in analyzing time trends in biologic fertility: protection bias.
One method of assessing biologic fertility is to measure time to pregnancy (TTP). Accidental pregnancies do not generate a valid TTP value and lead to nonrandom missing data if couples experiencing accidental pregnancies are more fertile than the general population. If factors affecting the rate of accidental pregnancies, such as availability of effective contraception and induced abortion, vary over time, then the result may be protection bias in the estimates of fertility time trends. Six European data sets were analyzed to investigate whether evidence of protection bias exists in TTP studies of fertility trends in Europe over the past 50 years. Couples experiencing accidental pregnancies tended to be more fertile than the general population. However, trends in accidental pregnancy rates were inconsistent across countries and were insufficient to produce substantial bias in fertility trends in simulated data. Where protection bias is suspected, the authors demonstrate use of 2 multiple imputation methods to generate realizations for the missing TTP values for accidental pregnancies. Simulation studies show that both methods successfully reduce or eliminate protection bias. The authors also demonstrate that standard sensitivity analyses for dealing with accidental pregnancies provide an upper bound on the extent of any bias.


Spherites in the midgut epithelial cells of the sugarcane borer parasitized by Cotesia flavipes.
Diatraea saccharalis, the main pest of sugarcane, has been controlled by Cotesia flavipes. Very little is known about the effect of parasitism on the host organs, including the midgut. The Lepidoptera midgut epithelium is composed of columnar, goblet, regenerative, and endocrine cells. Spherites have been described in columnar and regenerative cells of several Lepidoptera species, and presented a lot of functional meaning. We identified spherites in the midgut epithelial cells of non-parasitized D. saccharalis larvae analyzed the effect of parasitism on spherite morphology and distribution along the length of the midgut. Midgut fragments of both non-parasitized and parasitized larvae were processed for transmission electron microscopy. All the midgut epithelial cells showed spherites, but they were not preferentially located in a particular part of the cells. Parasitized larvae had more spherites, mainly in the columnar cells, than non-parasitized larvae. This observation was associated with an ionic imbalance within the insect host. Spherites were more abundant in the anterior midgut region than in other regions, which suggests that this region is involved in ion transport by intracellular and/or paracellular route. The morphological variability of spherites in the cells of parasitized larvae was related to the developmental stages of these structures.


Critical Care Air Transport Team severe traumatic brain injury short-term outcomes during flight for Operation Iraqi Freedom/Operation Enduring Freedom.
Our understanding of the expertise and equipment required to air transport injured soldiers with severe traumatic brain injuries (TBIs) continue to evolve. We conducted a retrospective chart review of characteristics, interventions required and short-term outcomes of patients with severe TBI managed by the US Air Force Critical Care Air Transport Teams (CCATTs) deployed in support of Operation Iraqi Freedom and Operation Enduring Freedom between 1 June 2007 and 31 August 2010. Patients were cared for based on guidelines given by the Brain Trauma Foundation and the Joint Theater Trauma System by non-neurosurgeon physicians with dedicated neurocritical care training. We report basic characteristics, injuries, interventions required and complications during transport. Intracranial haemorrhage was the most common diagnosis in this cohort. Most injuries were weapon related. During this study, there were no reported in-flight deaths. The majority of patients were mechanically ventilated. There were 45 patients who required at least one vasopressor to maintain adequate tissue perfusion, including four patients who required three or more. Some patients required intracranial pressure (ICP) management, treatment of diabetes insipidus and/or seizure prophylaxis medications. Air transport personnel must be prepared to provide standard critical care but also care specific to TBIs, including ICP control and management of diabetes insipidus. Although these patients and their potential complications are traditionally managed by neurosurgeons, those providers without neurosurgical backgrounds can be provided this training to help fill a wartime need. This study provides data for the future development of air transport guidelines for validating and clearing flight surgeons.


Better Outcomes through Learning, Data, Engagement, and Research (BOLDER) - a system for improving evidence and clinical practice in low and middle income countries.
Despite the many thousands of research studies published every year, evidence for making clinical decisions is often lacking. The main problem is that the evidence available is generated in conditions very different from those that prevail in routine clinical practice and with patients who are different. This is particularly a problem for low and middle income countries as most evidence is generated in high income countries. A group of clinicians, researchers, and policy makers met at Bellagio in Italy to consider how more relevant evidence might be generated. One answer is to conduct more pragmatic trials-those undertaken in routine clinical practice. The group thought that this might best be achieved by developing "learning health systems" in low and middle income countries. Learning health systems develop in communities that include clinicians, patients, researchers, improvement specialists, information technology specialists, managers, and policy makers and have a governance system that gives a voice to all those in the community. The systems focus on improving outcomes for patients, use a common dataset, and promote quality improvement and pragmatic research. Plans have been developed to create at least two learning systems in Africa.


Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.
Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants.


Role of atomic coherence in the propagation of two-color lasers in an autoionizing medium.
We study the role of atomic coherence in the propagation dynamics of two-color lasers in an autoionizing medium. By solving the coupled equations for atoms and fields simultaneously, it is found that the asymptotic value of the phase difference after a long propagation distance critically depends on the detuning from an autoionizing resonance and the asymmetry parameter, suggesting that inherent atomic coherence of an autoionizing system, which is absent in a bound state system, plays an important role during the propagation processes. Our numerical findings are consistent with our theoretical analysis using a series expansion method of the coupled equations.


A multicentre non-blinded randomised controlled trial to assess the impact of regular early specialist symptom control treatment on quality of life in malignant mesothelioma (RESPECT-MESO): study protocol for a randomised controlled trial.
Malignant pleural mesothelioma is an incurable cancer caused by exposure to asbestos. The United Kingdom has the highest death rate from mesothelioma in the world and this figure is increasing. Median survival is 8 to 12 months, and most patients have symptoms at diagnosis. The fittest patients may be offered chemotherapy with palliative intent. For patients not fit for systemic anticancer treatment, best supportive care remains the mainstay of management. A study from the United States examining advanced lung cancer showed that early specialist palliative care input improved patient health related quality of life and depression symptoms 12 weeks after diagnosis. While mesothelioma and advanced lung cancer share many symptoms and have a poor prognosis, oncology and palliative care services in the United Kingdom, and many other countries, vary considerably compared to the United States. The aim of this trial is to assess whether regular early symptom control treatment provided by palliative care specialists can improve health related quality of life in patients newly diagnosed with mesothelioma. This multicentre study is an non-blinded, randomised controlled, parallel group trial. A total of 174 patients with a new diagnosis of malignant pleural mesothelioma will be minimised with a random element in a 1:1 ratio to receive either 4 weekly regular early specialist symptom control care, or standard care. The primary outcome is health related quality of life for patients at 12 weeks. Secondary outcomes include health related quality of life for patients at 24 weeks, carer health related quality of life at 12 and 24 weeks, patient and carer mood at 12 and 24 weeks, overall survival and analysis of healthcare utilisation and cost. Current practice in the United Kingdom is to involve specialist palliative care towards the final weeks or months of a life-limiting illness. This study aims to investigate whether early, regular specialist care input can result in significant health related quality of life gains for patients with mesothelioma and if this change in treatment model is cost-effective. The results will be widely applicable to many institutions and patients both in the United Kingdom and internationally. Current controlled trials ISRCTN18955704. Date ISRCTN assigned: 31 January 2014.


Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.
To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.


Thin infrared imaging systems through multichannel sampling.
The size of infrared camera systems can be reduced by collecting low-resolution images in parallel with multiple narrow-aperture lenses rather than collecting a single high-resolution image with one wide-aperture lens. We describe an infrared imaging system that uses a three-by-three lenslet array with an optical system length of 2.3 mm and achieves Rayleigh criteria resolution comparable with a conventional single-lens system with an optical system length of 26 mm. The high-resolution final image generated by this system is reconstructed from the low-resolution images gathered by each lenslet. This is accomplished using superresolution reconstruction algorithms based on linear and nonlinear interpolation algorithms. Two implementations of the ultrathin camera are demonstrated and their performances are compared with that of a conventional infrared camera.


Current Trends in Patient-Reported Outcome Measures in Total Joint Arthroplasty: A Study of 4 Major Orthopaedic Journals.
More emphasis is being placed on patient-reported outcome measures (PROMs), but the myriad of PROMs makes standardization and cross-study comparison difficult. As the era of big data and massive total joint registries matures, it will be critical to identify and implement the best PROMs. All abstracts published in the years 2004, 2009, 2014, and 2016 in the Journal of Bone and Joint Surgery-American volume, the Bone and Joint Journal, Clinical Orthopedics and Related Research, and the Journal of Arthroplasty were reviewed. A PubMed search was performed with filters limiting results only to total knee, total hip, and unicompartmental knee arthroplasty articles with available abstracts. Each abstract was reviewed to identify all PROMs. Trends over time were evaluated using the Cochran-Armitage test. In the non-trend analysis, Pearson chi-square tests and one-way analysis of variance were performed. A total of 42 unique PROMs were used 1073 times across 644 studies. The number of PROMs in these 4 journals increased from 97 in 2004 to 228 in 2016 (P < .0001). The proportion of articles with more than one PROM increased from 20.6% in 2004 to 47.8% in 2016 (P = .0001). The most common PROMs used in total knee, total hip, and unicompartmental knee arthroplasty studies were the Knee Society Score, the Harris Hip Score, and the Oxford Knee Score, respectively. Providers and registries should consider the relative prevalence of published outcome measures when selecting which PROMs to use, to better facilitate future cross-study comparison.


Involvement of consumers in health technology assessment activities by Inahta agencies.
To obtain further information from members of the International Network of Agencies for Health Technology Assessment (INAHTA) on the involvement of consumers in their programs. A questionnaire for a survey was developed and sent to member agencies in November 2010. Survey responses were compared with those from an earlier survey conducted in 2005. Of the thirty-three agencies that provided responses, 67 percent involve consumers in some aspects of their health technology assessment (HTA) programs, compared with 57 percent in 2005. As in the earlier survey, most agencies reporting involvement have contact with consumer or patient organizations and a large minority also involve individual consumers. Summaries of HTA reports that are intended to be easily understood by consumers are prepared by 84 percent of the agencies, and 42 percent involve consumers in dissemination of HTA material. In both areas, there was some increase from the levels previously reported. The survey results suggest that there is a trend to increased involvement of consumers by the INAHTA agencies in their programs but that the level of involvement remains relatively limited. The manner of consumer participation varies between agencies.


Cerebral lateralization and early speech acquisition: a developmental scenario.
During the past ten years, research using Near-infrared Spectroscopy (NIRS) to study the developing brain has provided groundbreaking evidence of brain functions in infants. This paper presents a theoretically oriented review of this wealth of evidence, summarizing recent NIRS data on language processing, without neglecting other neuroimaging or behavioral studies in infancy and adulthood. We review three competing classes of hypotheses (i.e. signal-driven, domain-driven, and learning biases hypotheses) regarding the causes of hemispheric specialization for speech processing. We assess the fit between each of these hypotheses and neuroimaging evidence in speech perception and show that none of the three hypotheses can account for the entire set of observations on its own. However, we argue that they provide a good fit when combined within a developmental perspective. According to our proposed scenario, lateralization for language emerges out of the interaction between pre-existing left-right biases in generic auditory processing (signal-driven hypothesis), and a left-hemisphere predominance of particular learning mechanisms (learning-biases hypothesis). As a result of this completed developmental process, the native language is represented in the left hemisphere predominantly. The integrated scenario enables to link infant and adult data, and points to many empirical avenues that need to be explored more systematically.


Controversies in faith and health care.
Differences in religious faith-based viewpoints (controversies) on the sanctity of human life, acceptable behaviour, health-care technologies and health-care services contribute to the widespread variations in health care worldwide. Faith-linked controversies include family planning, child protection (especially child marriage, female genital mutilation, and immunisation), stigma and harm reduction, violence against women, sexual and reproductive health and HIV, gender, end-of-life issues, and faith activities including prayer. Buddhism, Christianity, Hinduism, Islam, Judaism, and traditional beliefs have similarities and differences in their viewpoints. Improved understanding by health-care providers of the heterogeneity of viewpoints, both within and between faiths, and their effect on health care is important for clinical medicine, public-health programmes, and health-care policy. Increased appreciation in faith leaders of the effect of their teachings on health care is also crucial. This Series paper outlines some faith-related controversies, describes how they influence health-care provision and uptake, and identifies opportunities for research and increased interaction between faith leaders and health-care providers to improve health care.


Genetic defects in human pericentrin are associated with severe insulin resistance and diabetes.
Genetic defects in human pericentrin (PCNT), encoding the centrosomal protein pericentrin, cause a form of osteodysplastic primordial dwarfism that is sometimes reported to be associated with diabetes. We thus set out to determine the prevalence of diabetes and insulin resistance among patients with PCNT defects and examined the effects of pericentrin depletion on insulin action using 3T3-L1 adipocytes as a model system. A cross-sectional metabolic assessment of 21 patients with PCNT mutations was undertaken. Pericentrin expression in human tissues was profiled using quantitative real-time PCR. The effect of pericentrin knockdown on insulin action and adipogenesis in 3T3-L1 adipocytes was determined using Oil red O staining, gene-expression analysis, immunoblotting, and glucose uptake assays. Pericentrin expression and localization also was determined in skeletal muscle. Of 21 patients with genetic defects in PCNT, 18 had insulin resistance, which was severe in the majority of subjects. Ten subjects had confirmed diabetes (mean age of onset 15 years [range 5-28]), and 13 had metabolic dyslipidemia. All patients without insulin resistance were younger than 4 years old. Knockdown of pericentrin in adipocytes had no effect on proximal insulin signaling but produced a twofold impairment in insulin-stimulated glucose uptake, approximately commensurate with an associated defect in cell proliferation and adipogenesis. Pericentrin was highly expressed in human skeletal muscle, where it showed a perinuclear distribution. Severe insulin resistance and premature diabetes are common features of PCNT deficiency but are not congenital. Partial failure of adipocyte differentiation may contribute to this, but pericentrin deficiency does not impair proximal insulin action in adipocytes.


Basal cell carcinoma.
Basal cell carcinoma (BCC) is the most common form of skin cancer, predominantly affecting the head and neck, and can be diagnosed clinically in most cases. Metastasis of BCC is rare, but localised tissue invasion and destruction can lead to morbidity. Incidence of BCC increases markedly after the age of 40 years, but incidence in younger people is rising, possibly as a result of increased sun exposure. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions on treatment response/recurrence (within 1 year of therapy) in people with basal cell carcinoma? What are the effects of interventions on long-term recurrence (a minimum of 2 years after treatment) in people with basal cell carcinoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: cryotherapy/cryosurgery, curettage and cautery/electrodesiccation, fluorouracil, imiquimod 5% cream, photodynamic therapy, and surgery (conventional or Mohs' micrographic surgery).


Effects of training on stress-related behavior of the common marmoset (Callithrix jacchus) in relation to coping with routine husbandry procedures.
Using positive reinforcement, J. McKinley trained 12 common marmosets (Callithrix jacchus) to provide urine samples on request. The study then exposed the marmosets to mildly stressful, routine husbandry procedures (i.e., capture and weighing). The nonhuman animals spent less time inactive poststressor as opposed to prestressor. L. Bassett collected matched behavioral data from 12 nontrained marmosets who were less accustomed to human interaction. These animals spent significantly more time self-scratching and locomoting as well as less time inactive, poststressor. Collapsed data from the 2 populations showed increased scent marking, poststressor. These results suggest that locomotion, self-scratching, and scent marking are useful, noninvasive behavioral measures of stress and, thus, reduced welfare in the common marmoset. Overall, nontrained animals showed more self-scratching than did their trained counterparts. It was not possible to collect urine from nontrained marmosets. In response to the stressor, however, trained animals showed no significant change in excreted urinary cortisol. These results suggest that training marmosets may allow them to cope better with routine laboratory procedures.


Voice processing in dementia: a neuropsychological and neuroanatomical analysis.
Voice processing in neurodegenerative disease is poorly understood. Here we undertook a systematic investigation of voice processing in a cohort of patients with clinical diagnoses representing two canonical dementia syndromes: temporal variant frontotemporal lobar degeneration (n = 14) and Alzheimer's disease (n = 22). Patient performance was compared with a healthy matched control group (n = 35). All subjects had a comprehensive neuropsychological assessment including measures of voice perception (vocal size, gender, speaker discrimination) and voice recognition (familiarity, identification, naming and cross-modal matching) and equivalent measures of face and name processing. Neuroanatomical associations of voice processing performance were assessed using voxel-based morphometry. Both disease groups showed deficits on all aspects of voice recognition and impairment was more severe in the temporal variant frontotemporal lobar degeneration group than the Alzheimer's disease group. Face and name recognition were also impaired in both disease groups and name recognition was significantly more impaired than other modalities in the temporal variant frontotemporal lobar degeneration group. The Alzheimer's disease group showed additional deficits of vocal gender perception and voice discrimination. The neuroanatomical analysis across both disease groups revealed common grey matter associations of familiarity, identification and cross-modal recognition in all modalities in the right temporal pole and anterior fusiform gyrus; while in the Alzheimer's disease group, voice discrimination was associated with grey matter in the right inferior parietal lobe. The findings suggest that impairments of voice recognition are significant in both these canonical dementia syndromes but particularly severe in temporal variant frontotemporal lobar degeneration, whereas impairments of voice perception may show relative specificity for Alzheimer's disease. The right anterior temporal lobe is likely to have a critical role in the recognition of voices and other modalities of person knowledge.


Diabetic kidney disease in FVB/NJ Akita mice: temporal pattern of kidney injury and urinary nephrin excretion.
Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process.


A comparative study of 2 fluoride-based mouthrinses.
The purpose of this study was to compare the effectiveness of 2 mouthrinses (conventional Meridol and alcohol-free Meridol). A controlled, single-blind clinical study of 3 weeks' duration was conducted on 80 adult subjects in good general health and without severe periodontitis (probing depths no deeper than 4 mm). The mouthrinses supplemented regular measures of oral hygiene for the reduction of plaque and gingivitis. In preliminary examinations to determine general conditions of oral health, especially the level of plaque, gingivitis, and periodontal findings, the approximal plaque index, sulcular bleeding index, and gingival index were established for each subject. Afterward the subjects were provided with a professional toothcleaning, as required. Each subject was randomly provided with 1 of the 2 mouthrinses, to be used 3 times daily in addition to routine oral health measures. The 3 indexes were reevaluated after 3 weeks; in addition, an optional stain index was employed. In both subject groups, a statistically significant reduction in plaque accumulation, as well as a reduction in inflammation and the tendency to bleeding, was observed. Reversible staining of the teeth and tongue was observed in fewer than one third of the subjects in both groups. Comparison of the 2 Meridol mouthrinses revealed no difference in effectiveness related to the alcohol content.


Global Measurements of Stratospheric Mountain Waves from Space.
Temperatures acquired by the Cryogenic Infrared Spectrometers and Telescopes for the Atmosphere (CRISTA) during shuttle mission STS-66 have provided measurements of stratospheric mountain waves from space. Large-amplitude, long-wavelength mountain waves at heights of 15 to 30 kilometers above the southern Andes Mountains were observed and characterized, with vigorous wave breaking inferred above 30 kilometers. Mountain waves also occurred throughout the stratosphere (15 to 45 kilometers) over a broad mountainous region of central Eurasia. The global distribution of mountain wave activity accords well with predictions from a mountain wave model. The findings demonstrate that satellites can provide the global data needed to improve mountain wave parameterizations and hence global climate and forecast models.


Novel Mitoviruses and a Unique Tymo-Like Virus in Hypovirulent and Virulent Strains of the Fusarium Head Blight Fungus, Fusarium boothii.
Hypovirulence of phytopathogenic fungi are often conferred by mycovirus(es) infections and for this reason many mycoviruses have been characterized, contributing to a better understanding of virus diversity. In this study, three strains of Fusarium head blight fungus (Fusarium boothii) were isolated from Ethiopian wheats as dsRNA-carrying strains: hypovirulent Ep-BL13 (>10, 3 and 2.5 kbp dsRNAs), and virulent Ep-BL14 and Ep-N28 (3 kbp dsRNA each) strains. The 3 kbp-dsRNAs shared 98% nucleotide identity and have single ORFs encoding a replicase when applied to mitochondrial codon usage. Phylogenetic analysis revealed these were strains of a new species termed Fusarium boothii mitovirus 1 in the genus Mitovirus. The largest and smallest dsRNAs in Ep-BL13 appeared to possess single ORFs and the smaller was originated from the larger by removal of its most middle part. The large dsRNA encoded a replicase sharing the highest amino acid identity (35%) with that of Botrytis virus F, the sole member of the family Gammaflexiviridae. Given that the phylogenetic placement, large genome size, simple genomic and unusual 3'-terminal RNA structures were far different from members in the order Tymovirales, the virus termed Fusarium boothii large flexivirus 1 may form a novel genus and family under the order.


Energy intake and risk of postmenopausal breast cancer: an expanded analysis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort.
Although animal experiments have consistently shown a positive relationship between breast cancer and energy intake, evidence from human studies remains inconclusive. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort, 29,170 women, ages 55 to 75 years, who successfully completed a food frequency questionnaire (FFQ) at entry (1993-2001), were followed through 2007, and 1,319 incident breast cancers were ascertained (median time from FFQ completion to diagnosis, 4.4 years). Women in the highest quartile of energy intake, relative to the lowest, had modestly, but significantly, increased breast cancer risk [multivariate relative risk (RR), 1.21; 95% confidence interval (95% CI), 1.03-1.42; P(trend) = 0.03]. The inclusion of body mass index and physical activity in the model reduced risk slightly (RR, 1.18; 95% CI, 1.00-1.39; P(trend) = 0.07). However, in similar analyses using energy intake from a FFQ administered approximately five years after entry (27,428 women; 806 incident breast cancers; median time from FFQ completion to diagnosis, 2.7 years), women in the highest and lowest quartiles of energy intake had similar risk. When follow-up time after the first FFQ was divided into three 4-year periods, the multivariate RRs for high versus low energy intake increased from 1.21 to 1.37 to 1.55 with increasing time since dietary assessment. Although the divergent results for the two FFQs could be due to subtle questionnaire differences, our findings suggest a modest positive association between energy intake and postmenopausal breast cancer that strengthens with time since dietary assessment.


Ground-State Spin Blockade in a Single-Molecule Junction.
It is known that the quantum mechanical ground state of a nanoscale junction has a significant impact on its electrical transport properties. This becomes particularly important in transistors consisting of a single molecule. Because of strong electron-electron interactions and the possibility of accessing ground states with high spins, these systems are eligible hosts of a current-blockade phenomenon called a ground-state spin blockade. This effect arises from the inability of a charge carrier to account for the spin difference required to enter the junction, as that process would violate the spin selection rules. Here, we present a direct experimental demonstration of a ground-state spin blockade in a high-spin single-molecule transistor. The measured transport characteristics of this device exhibit a complete suppression of resonant transport due to a ground-state spin difference of 3/2 between subsequent charge states. Strikingly, the blockade can be reversibly lifted by driving the system through a magnetic ground-state transition in one charge state, using the tunability offered by both magnetic and electric fields.


Factors influencing the utilization of research findings by health policy-makers in a developing country: the selection of Mali's essential medicines.
Research findings are increasingly being recognized as an important input in the formation of health policy. There is concern that research findings are not being utilized by health policy-makers to the extent that they could be. The factors influencing the utilization of various types of research by health policy-makers are beginning to emerge in the literature, however there is still little known about these factors in developing countries. The object of this study was to explore these factors by examining the policy-making process for a pharmaceutical policy common in developing countries; an essential medicines list. A study of the selection and updating of Mali's national essential medicines list was undertaken using qualitative methods. In-depth semi-structured interviews and a natural group discussion were held with national policy-makers, most specifically members of the national commission that selects and updates the country's list. The resulting text was analyzed using a phenomenological approach. A document analysis was also performed. Several factors emerged from the textual data that appear to be influencing the utilization of health research findings for these policy-makers. These factors include: access to information, relevance of the research, use of research perceived as a time consuming process, trust in the research, authority of those who presented their view, competency in research methods, priority of research in the policy process, and accountability. Improving the transfer of research to policy will require effort on the part of researchers, policy-makers, and third parties. This will include: collaboration between researchers and policy-makers, increased production and dissemination of relevant and useful research, and continued and improved technical support from networks and multi-national organizations. Policy-makers from developing countries will then be better equipped to make informed decisions concerning their health policy issues.


The role of phytoestrogens in the prevention and treatment of osteoporosis in ovarian hormone deficiency.
Ovarian hormone deficiency is a major risk factor for osteoporosis in postmenopausal women. Hormone replacement therapy (HRT) is perhaps the most effective treatment, as it has been demonstrated to both reduce the rate of bone loss and risk of fracture, including hip fracture. However, not all women who may benefit from HRT are willing to initiate this treatment due to fear of cancer and contraindications. Other therapeutic agents currently available are also associated with certain adverse effects. As a result, postmenopausal women are more inclined to use natural remedies to alleviate postmenopausal symptoms and help reduce their risk for chronic diseases such as osteoporosis. Recent reports support the notion that certain bioactive constituents, e.g., phytoestrogens, in plants play a role in maintaining or improving skeletal health. The main consumable plant sources of phytoestrogens include isoflavones and lignans found mainly in soybeans and flaxseed, respectively. Although this paper primarily focuses on the effects of soy protein or its isoflavones on bone, additional statements regarding the role of flaxseed and dried plums, a rich source of polyphenols, with respect to bone will be made.


Improved calibration of mass stopping power in low density tissue for a proton pencil beam algorithm.
Dose distributions for proton therapy treatments are almost exclusively calculated using pencil beam algorithms. An essential input to these algorithms is the patient model, derived from x-ray computed tomography (CT), which is used to estimate proton stopping power along the pencil beam paths. This study highlights a potential inaccuracy in the mapping between mass density and proton stopping power used by a clinical pencil beam algorithm in materials less dense than water. It proposes an alternative physically-motivated function (the mass average, or MA, formula) for use in this region. Comparisons are made between dose-depth curves calculated by the pencil beam method and those calculated by the Monte Carlo particle transport code MCNPX in a one-dimensional lung model. Proton range differences of up to 3% are observed between the methods, reduced to <1% when using the MA function. The impact of these range errors on clinical dose distributions is demonstrated using treatment plans for a non-small cell lung cancer patient. The change in stopping power calculation methodology results in relatively minor differences in dose when plans use three fields, but differences are observed at the 2%-2 mm level when a single field uniform dose technique is adopted. It is therefore suggested that the MA formula is adopted by users of the pencil beam algorithm for optimal dose calculation in lung, and that a similar approach is considered when beams traverse other low density regions such as the paranasal sinuses and mastoid process.


250 mW, 1.5 microm monolithic passively mode-locked slab-coupled optical waveguide laser.
We report the demonstration of a 1.5 microm InGaAsP mode-locked slab-coupled optical waveguide laser (SCOWL) producing 10 ps pulses with energies of 58 pJ and average output powers of 250 mW at a repetition rate of 4.29 GHz. To the best of our knowledge, this is the first passively mode-locked slab-coupled optical waveguide laser. The large mode and low confinement factor of the SCOWL architecture allows the realization of monolithic mode-locked lasers with high output power and pulse energy. The laser output is nearly diffraction limited with M2 values less than 1.2 in both directions.


Improving precision of proximity ligation assay by amplified single molecule detection.
Proximity ligation assay (PLA) has been proven to be a robust protein detection method. The technique is characterized by high sensitivity and specificity, but the assay precision is probably limited by the PCR readout. To investigate this potential limitation and to improve precision, we developed a digital proximity ligation assay for protein measurement in fluids based on amplified single molecule detection. The assay showed significant improvements in precision, and thereby also detection sensitivity, over the conventional real-time PCR readout.


A sensitive micro-immunoassay using beta-galactosidase/anti-beta-galactosidase complexes.
This paper describes a new sensitive microELISA based on enzyme/anti-enzyme complexes following an unlabelled antibody bridging step. beta-Galactosidase/anti-beta-galactosidase complexes were made using a monoclonal antibody raised against bacterial (E. coli) beta-galactosidase and enzyme activity was quantified with a fluorogenic substrate. Because of its high sensitivity the assay is particularly suitable for the detection of limited amounts of antigen. One application illustrated is the analysis of Class I and Class II histocompatibility antigens on peripheral blood lymphocytes using 5000 cells/well in 60-well Terasaki or 96-well microtitre plates.


Self-efficacy as a relevant construct in understanding sexual response and dysfunction.
While self-efficacy has been widely used to explain and treat various biobehavioral responses, few investigations have examined this concept in the context of sexual response and dysfunction. In this study, the authors constructed a measure of sexual self-efficacy, investigated whether it differentiated men with and without sexual dysfunction, and determined the utility of this construct by exploring its relation to other variables known to be related to erectile dysfunction in a sample of 60 men with erectile dysfunction and 14 functional men visiting a urology clinic. The sexual self-efficacy index differentiated men with and without erectile dysfunction, and general linear modeling showed that the index did indeed relate to other variables known to affect sexual and emotional response during a partnered sexual experience. These findings suggest that, as a unifying construct that predicts cognitive, affective, motivational, and behavioral responses, sexual self-efficacy has the potential to play an important role in the assessment of effective treatments for sexual problems.


Work-related musculoskeletal disorders among nurses in Ibadan, South-west Nigeria: a cross-sectional survey.
Musculoskeletal disorders represent a significant occupational problem among nurses; however, data on musculoskeletal health of nurses in Sub-Sahara Africa are sparse. This study sought to determine the lifetime, 12-months period and point prevalence of work-related musculoskeletal disorders (WMSDs); the associated job risk factors and the coping strategies toward reducing the risk among nurses from selected hospitals in Ibadan, South-west Nigeria A previously validated self administered questionnaire which sought information on demographics, prevalence and pattern of WMSDs, associated job risk factors and coping strategies was employed as the survey instrument. A total of 160 questionnaires were distributed to nurses in the different hospitals but 128 questionnaires were returned yielding an 80% response rate. 10 of the returned questionnaires were excluded because of incomplete data. Eighty-four point four percent of the nurses have had WMSDs once or more in their occupational lives. The 12-months period and point prevalence rate of WMSDs at any body region was 78% and 66.1% respectively. WMSDs occurred mostly in low back (44.1%), neck (28.0%), and knees (22.4%). 30.3% treated themselves or had visited other health practitioners for care. Nurses with > 20 years of clinical experience are about 4 times more likely to develop WMSDs (OR 3.81; CI 1.08-13.4) than those with 11-20 years experience. Working in the same positions for long periods (55.1%), lifting or transferring dependent patients (50.8%) and treating an excessive number of patients in one day (44.9%) were the most perceived job risk factors for WMSDs. Getting help in handling heavy patients (50.4%), modification of nursing procedures in order to avoid re-injury (45.4%), and modifying patient's/nurse position (40.3%) were the top three coping strategies. A high proportion of Nigerian nurses reported WMSDs at some body site in their occupational lives with the low back being injured most often. Education programmes on prevention and coping strategies for musculoskeletal disorders are recommended for nurses in order to reduce the rate of occupational hazards and also promote efficiency in patient care.


Theory of diffraction of vortex beams from structured apertures and generation of elegant elliptical vortex Hermite-Gaussian beams.
In this work, a comprehensive analytic study of the diffraction of vortex beams from structured apertures is presented. We formulate the near- and far-field diffraction of a vortex beam from an aperture having an arbitrary functionality in the Cartesian coordinates by two general and different approaches. We show that each of the resulting diffraction patterns can be determined by a number of successive derivatives of the 2D Fourier transform of the corresponding hypothetical aperture function or equally can be obtained by a summation of 2D Fourier transforms of the corresponding modified aperture function. We implement both introduced analytic approaches in predicting the diffraction of a vortex beam from an elliptic Gaussian aperture, an elliptic Gaussian phase mask, and a hyperbolic Gaussian phase mask in the near- and far-field regimes. It is shown that the predicted diffraction patterns by both these approaches are exactly the same. It is shown that the diffraction of a vortex beam from an elliptic Gaussian aperture at the far-field regime forms a light beam that belongs to a family of light beams we call elegant elliptical vortex Hermite-Gaussian beams. In addition, the diffractions of a vortex beam from a Fresnel zone plate in general form for the on- and off-axis situations are formulated, and sinusoidal and binary zone plates are investigated in detail. Our general analytic formula can be used for a large variety of apertures including off-center situations and asymmetrical cases.


Evaluating the Quality of Health Information in a Changing Digital Ecosystem.
Critical evaluation of online health information has always been central to consumer health informatics. However, with the emergence of new Web media platforms and the ubiquity of social media, the issue has taken on a new dimension and urgency. At the same time, many established existing information quality evaluation guidelines address information characteristics other than the content (eg, authority and currency), target information creators rather than users as their main audience, or do not address information presented via novel Web technologies. The aim of this formative study was to (1) develop a methodological approach for analyzing health-related Web pages and (2) apply it to a set of relevant Web pages. This qualitative study analyzed 25 type 2 diabetes pages, which were derived from the results of a Google search with the keywords "diabetes," "reversal," and "natural." The coding scheme, developed via a combination of theory- and data-driven approaches, includes 5 categories from existing guidelines (resource type, information authority, validity of background information sources, objectivity, and currency) and 7 novel categories (treatment or reversal method, promises and certainty, criticisms of establishment, emotional appeal, vocabulary, rhetoric and presentation, and use of science in argumentation). The coding involves both categorical judgment and in-depth narrative characterization. On establishing satisfactory level of agreement on the narrative coding, the team coded the complete dataset of 25 pages. The results set included "traditional" static pages, videos, and digitized versions of printed newspapers or magazine articles. Treatments proposed by the pages included a mixture of conventional evidence-based treatments (eg, healthy balanced diet exercise) and unconventional treatments (eg, dietary supplements, optimizing gut flora). Most pages either promised or strongly implied high likelihood of complete recovery. Pages varied greatly with respect to the authors' stated background and credentials as well as the information sources they referenced or mentioned. The majority included criticisms of the traditional health care establishment. Many sold commercial products ranging from dietary supplements to books. The pages frequently used colloquial language. A significant number included emotional personal anecdotes, made positive mentions of the word cure, and included references to nature as a positive healing force. Most pages presented some biological explanations of their proposed treatments. Some of the explanations involved the level of complexity well beyond the level of an educated layperson. Both traditional and data-driven categories of codes used in this work yielded insights about the resources and highlighted challenges faced by their users. This exploratory study underscores the challenges of consumer health information seeking and the importance of developing support tools that would help users seek, evaluate, and analyze information in the changing digital ecosystem.


The Second ASRA Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine: Executive Summary 2015.
Neurologic injury associated with regional anesthetic or pain medicine procedures is extremely rare. The Second American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine focuses on those complications associated with mechanical, ischemic, or neurotoxic injury of the neuraxis or peripheral nervous system. As with the first advisory, this iteration does not focus on hemorrhagic or infectious complications or local anesthetic systemic toxicity, all of which are the subjects of separate practice advisories. The current advisory offers recommendations to aid in the understanding and potential limitation of rare neurologic complications that may arise during the practice of regional anesthesia and/or interventional pain medicine. The Second American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Neurologic Complications Associated With Regional Anesthesia and Pain Medicine updates information that was originally presented at the Society's first open forum on this subject (2005) and published in 2008. Portions of the second advisory were presented in an open forum (2012) and are herein updated, with attention to those topics subject to evolving knowledge since the first and second advisory conferences. The second advisory briefly summarizes recommendations that have not changed substantially. New to this iteration of the advisory is information related to the risk of nerve injury inherent to common orthopedic surgical procedures. Recommendations are expanded regarding the preventive role of various monitoring technologies such as ultrasound guidance and injection pressure monitoring. New clinical recommendations focus on emerging concerns including spinal stenosis and vertebral canal pathologies, blood pressure management during neuraxial anesthesia, administering blocks in anesthetized or deeply sedated patients, patients with preexisting neurologic disease, and inflammatory neuropathies. An updated diagnostic and treatment algorithm is presented.


The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription.
Huntington's Disease (HD) is caused by an expansion of a polyglutamine tract within the huntingtin (htt) protein. Pathogenesis in HD appears to include the cytoplasmic cleavage of htt and release of an amino-terminal fragment capable of nuclear localization. We have investigated potential consequences to nuclear function of a pathogenic amino-terminal region of htt (httex1p) including aggregation, protein-protein interactions, and transcription. httex1p was found to coaggregate with p53 in inclusions generated in cell culture and to interact with p53 in vitro and in cell culture. Expanded httex1p represses transcription of the p53-regulated promoters, p21(WAF1/CIP1) and MDR-1. httex1p was also found to interact in vitro with CREB-binding protein (CBP) and mSin3a, and CBP to localize to neuronal intranuclear inclusions in a transgenic mouse model of HD. These results raise the possibility that expanded repeat htt causes aberrant transcriptional regulation through its interaction with cellular transcription factors which may result in neuronal dysfunction and cell death in HD.


Neuronal changes in psoriasis exacerbation.
The nervous system contributes to inflammatory skin diseases. Objective The aim of this investigation was to study the neuronal contribution to psoriasis at the remission and exacerbation phases. We examined the expression of the neuronal markers protein gene product 9.5 (PGP 9.5), growth-associated protein-43 (GAP-43) and substance P, in addition to its receptor (R), neurokinin-1R (NK-1R) in psoriatic skin from seven female patients at remission and exacerbation, using immunohistochemistry. The number of epidermal PGP 9.5 immunoreactive nerve fibres in the involved skin during exacerbation was decreased (P < 0.01) compared to involved skin at remission and non-involved skin at the exacerbation phase. GAP-43-positive nerve fibres were decreased (P < 0.05) in the involved skin in contrast to non-involved skin, during exacerbation. Substance P expression was seen on both immunoreactive nerve fibres and cells with a down-regulation (P < 0.01) in the number of positive nerve fibres in the involved skin compared to non-involved skin, at the exacerbation phase. The number of substance P-positive cells was slightly lower in the involved skin at exacerbation than at remission. The number of NK-1R immunoreactive cells was increased (P < 0.01) in the involved skin in contrast to non-involved skin, at the exacerbation phase. Our findings suggest a crosstalk between the nervous system and inflammation during psoriasis exacerbation in the form of an altered expression of nerve fibres, substance P and its NK-1R.


Adiponectin, leptin and insulin in breast milk: associations with maternal characteristics and infant body composition in the first year of life.
Breastfeeding may protect against excessive weight gain during infancy. However, the breast milk components responsible for this effect are unknown. We examined the variation of three breast milk hormones (adiponectin, leptin and insulin) according to maternal characteristics and determined their association with infant body composition. We studied a representative subset of 430 breastfed infants in the CHILD birth cohort. Breast milk was collected at 4 months postpartum and hormone concentrations were measured using the MesoScale Discovery System. Weight-for-length (WFL) and body mass index (BMI) z-scores were calculated according to the World Health Organization reference standard from infant anthropometrics measured at 4 months and 1 year. Maternal BMI and demographics were self-reported. Breast milk hormone concentrations varied widely between mothers. The geometric mean (range) was 19.4 (3.7-74.4) ngml-1 for adiponectin; 361 (31-3968) pgml-1 for leptin; and 589 (53-5557) pgml-1 for insulin. Maternal BMI was positively correlated with breast milk insulin (r=+0.40, P<0.0001) and leptin (r=+0.71, P<0.0001), but not adiponectin (r=-0.02, P=0.68). Breast milk hormone concentrations were also associated with maternal ethnicity, parity and breastfeeding exclusivity at sample collection. Independent of these factors and maternal diabetes, smoking and breastfeeding duration, higher breast milk leptin was associated with lower infant WFL z-score at 4 months (β -0.67, 95% confidence interval (CI): -1.17, -0.17 for highest vs lowest quintile) and 1 year (β -0.58, 95% CI: -1.02, -0.14). Insulin showed a U-shaped association, with intermediate concentrations predicting the lowest infant WFL z-score at 4 months (β -0.51, 95% CI: -0.87, -0.15 for third vs lowest quintile) and 1 year (β -0.35, 95% CI: -0.66, -0.04). Similar results were seen with infant BMI. Breast milk adiponectin was not significantly associated with infant body composition. Breast milk hormone concentrations were associated with several fixed and modifiable maternal characteristics. Higher concentrations of leptin and intermediate concentrations of insulin were associated with lower infant WFL in the first year of life.


Use of the Bruininks-Oseretsky test of motor proficiency in occupational therapy.
In addition to the need for good measurement tools in occupational therapy, there is a need for the tools to be used knowledgeably. The purpose of this article is to investigate the usefulness of the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) for both descriptive (diagnostic) and evaluative (change over time) purposes. The typical profile of subtest scores for children with mild motor problems revealed that certain subtests of the BOTMP may be better indicators of motor problems for these children than others. An analysis also was performed to compare the use of raw (point) scores with standard (age-adjusted) scores in evaluating change. Four subtests that provide a greater degree of discrimination between children with and without motor problems were identified. Raw (points) scores were found to provide a more valid measure of change over time than standard (age-related) scores. We recommend that, for clinical use, the BOTMP subtest standard scores be used for diagnostic purposes and that the raw scores be used for evaluative purposes.


Self-similarity and multifractality in human brain activity: A wavelet-based analysis of scale-free brain dynamics.
The temporal structure of macroscopic brain activity displays both oscillatory and scale-free dynamics. While the functional relevance of neural oscillations has been largely investigated, both the nature and the role of scale-free dynamics in brain processing have been disputed. Here, we offer a novel method to rigorously enrich the characterization of scale-free brain activity using a robust wavelet-based assessment of self-similarity and multifractality. For this, we analyzed human brain activity recorded with magnetoencephalography (MEG) while participants were at rest or performing a visual motion discrimination task. First, we report consistent infraslow (from 0.1 to 1.5 Hz) scale-free dynamics (i.e., self-similarity and multifractality) in resting-state and task data. Second, we observed a fronto-occipital gradient of self-similarity reminiscent of the known hierarchy of temporal scales from sensory to higher-order cortices; the anatomical gradient was more pronounced in task than in rest. Third, we observed a significant increase of multifractality during task as compared to rest. Additionally, the decrease in self-similarity and the increase in multifractality from rest to task were negatively correlated in regions involved in the task, suggesting a shift from structured global temporal dynamics in resting-state to locally bursty and non Gaussian scale-free structures during task. We showed that the wavelet leader based multifractal approach extends power spectrum estimation methods in the way of characterizing finely scale-free brain dynamics. Altogether, our approach provides novel fine-grained characterizations of scale-free dynamics in human brain activity.


Factors affecting outcome in schizophrenia and their relevance for psychopharmacological treatment.
A major focus of current treatment research in schizophrenia is the determinants of long-term outcome, including functional outcome and general medical well being, rather than just specific domains of psychopathology such as positive and negative symptoms, mood symptoms, and cognitive impairment. This focus does not negate the importance of the latter issues but sees them as factors contributing to long-term outcome to variable extents. A long-term treatment focus facilitates a more clinically relevant assessment of benefits versus risks of available treatments. For instance, atypical antipsychotic drugs as a group have clear advantages for several important domains of efficacy that may influence long-term outcome, but are also more expensive over the long term. Use of some agents may also result in deleterious physical health consequences as well as large additional costs over the long term owing to metabolic adverse effects. The present paper focuses on several key issues in schizophrenia which are important determinants of long-term outcome in schizophrenia, or influence choice of antipsychotic drugs, or both, including: (i) duration of untreated psychosis; (ii) impact of relapse on long-term outcome; (iii) limited efficacy for specific domains of psychopathology of current treatments; (iv) mortality owing to suicide; and (v) mortality owing to other causes (e.g. cardiovascular disease).


Fechner's aesthetics revisited.
Gustav Fechner is widely respected as a founding father of experimental psychology and psychophysics but fewer know of his interests and work in empirical aesthetics. In the later 1800s, toward the end of his career, Fechner performed experiments to empirically evaluate the beauty of rectangles, hypothesizing that the preferred shape would closely match that of the so-called 'golden rectangle'. His findings confirmed his suspicions, but in the intervening decades there has been significant evidence pointing away from that finding. Regardless of the results of this one study, Fechner ushered in the notion of using a metric to evaluate beauty in a psychophysical way. In this paper, we recreate the experiment using more naturalistic stimuli. We evaluate subjects' preferences against models that use various types of object complexity as metrics. Our findings that subjects prefer either very simple or very complex objects runs contrary to the hypothesized results, but are systematic none the less. We conclude that there are likely to be useful measures of aesthetic preference but they are likely to be complicated by the difficulty in defining some of their constituent parts.


Mental health research on scheduled tribes in India.
The burden of mental illness among the scheduled tribe (ST) population in India is not known clearly. The aim was to identify and appraise mental health research studies on ST population in India and collate such data to inform future research. Studies published between January 1980 and December 2018 on STs by following exclusion and inclusion criteria were selected for analysis. PubMed, PsychINFO, Embase, Sociofile, Cinhal, and Google Scholar were systematically searched to identify relevant studies. Quality of the included studies was assessed using an appraisal tool to assess the quality of cross-sectional studies and Critical Appraisal Checklist developed by Critical Appraisal Skills Programme. Studies were summarized and reported descriptively. Thirty-two relevant studies were found and included in the review. Studies were categorized into the following three thematic areas: alcohol and substance use disorders, common mental disorders and sociocultural aspects, and access to mental health-care services. Sociocultural factors play a major role in understanding and determining mental disorders. This study is the first of its kind to review research on mental health among the STs. Mental health research conducted among STs in India is limited and is mostly of low-to-moderate quality. Determinants of poor mental health and interventions for addressing them need to be studied on an urgent basis.


Applications of exogenous mesenchymal stem cells and low intensity pulsed ultrasound enhance fracture healing in rat model.
The present study aimed to investigate the effects of combined treatment of exogenous mesenchymal stem cells (MSCs) and low intensity pulsed ultrasound (LIPUS) on fracture healing by comparing LIPUS-MSC, MSC and control (CTL) groups. Radiography and quantitative callus width/area demonstrated that the MSC-LIPUS group had the best healing, MSC group the second and CTL group the poorest with significant differences among each at different time points. Micro-CT data supported that MSC-LIPUS had the highest bone volume/tissue volume. Histomorphometry showed a significantly faster remodeling in late phase in MSC-LIPUS and MSC groups. These indicated that the combined treatment of MSCs and LIPUS was beneficial to fracture healing. Regenerative power and homing ability of MSCs were shown by promotion in fracture healing and locally found green fluorescent protein (GFP)-labeled MSCs at fracture calluses. This evidence reflects that co-treatment of MSCs and LIPUS may be developed as an intervention for delayed union or nonunion.


Prevalence of and risk factors for tuberculin positivity and skin test anergy in HIV-1-infected and uninfected at-risk women. Women's Interagency HIV Study (WIHS).
To determine differences in rates of reactivity to purified protein derivative (PPD) tuberculin and of skin test anergy in relationship to serostatus, immune status, demographic characteristics, and other risk factors in women infected with or at high risk for infection with HIV-1; and to compare the usefulness of three different antigens in assessing delayed type hypersensitivity. Cross-sectional analysis of baseline data in a multicenter prospective cohort study of 1343 HIV-1-seropositive and 390 seronegative but at-risk women recruited from sites of HIV primary care and through community-based outreach for a longitudinal cohort study. 4.7% of the 1343 HIV-1-seropositive women and 15.4% of the 390 HIV-seronegative women were tuberculin-positive (p < .001). A lower threshold in millimeters of induration for tuberculin reactivity among HIV-seropositive women resulted in a smaller difference between the seropositive and the seronegative groups. Even when a 2-mm threshold was used in HIV-seropositive respondents, with a 10-mm threshold among seronegative participants, the difference between the seropositive (6.9% reactive) and the seronegative (15.4% reactive) groups remained statistically significant (p < .001). Limiting analysis to women who responded to the non-PPD antigens did not eliminate the differences in PPD reactivity between the HIV-seropositive and HIV-seronegative women. In multivariate analysis, tuberculin reactivity was associated with HIV-negative serostatus, a history of tuberculosis infection or disease, geographic site, and CD4 count >200 cells/mm3 in the HIV-seropositive women. In all, 41% of HIV-seropositive women and 12% of seronegative women were anergic (p < .001). Candida antigen had the lowest response rates. In multivariate analyses, only HIV-serostatus and CD4 cell counts in HIV-seropositive women were significantly associated with anergy. In this community-based cohort of HIV-seropositive and HIV-seronegative women, we found significant differences between the seronegative and seropositive women even with a lower threshold of induration defining PPD reactivity among seropositive women and among women not anergic to the non-PPD antigens. Prevalence of PPD reactivity was higher than in previously described in cohorts of homosexual men, but lower than in cohorts of predominantly male injection drug users. Rates of anergy were similar to those in most previously described cohorts.


Non-antibiotic strategies for sepsis.
Sepsis and septic shock remain a considerable therapeutic challenge. Despite significant advances in supportive care and the availability of potent, broad-spectrum antibiotics, the overall mortality due to sepsis is still approximately 35%, and this increases to 60% if patients develop septic shock. Antibiotics constitute a necessary part of the treatment of sepsis, and there is probably considerable scope to improve the way in which they are used. Nevertheless, antibiotics alone, even used optimally, are probably not sufficient to substantially reduce the mortality that accompanies the multiorgan failure that occurs in septic patients. For this reason, considerable efforts have been expended in developing non-antibiotic (or so-called adjunctive) forms of treatment, and here the general approaches to these types of treatment are reviewed. There are three main categories: improvements in supportive care, treatments aimed at bacterial virulence factors, and treatments aimed at host mediators. This is not intended to be a comprehensive review, but rather to provide examples in each category to illustrate the general principles-and the hurdles-that have characterized these approaches to therapy.


Reproduction numbers for epidemic models with households and other social structures. I. Definition and calculation of R0.
The basic reproduction number R(0) is one of the most important quantities in epidemiology. However, for epidemic models with explicit social structure involving small mixing units such as households, its definition is not straightforward and a wealth of other threshold parameters has appeared in the literature. In this paper, we use branching processes to define R(0), we apply this definition to models with households or other more complex social structures and we provide methods for calculating it.


Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo.
Genetic studies have identified the key signalling pathways and developmentally regulated transcription factors that govern cell lineage allocation and axis patterning in the early mammalian embryo. Recent advances have uncovered details of the molecular circuits that tightly control cell growth and differentiation in the mammalian embryo from the blastocyst stage, through the establishment of initial anterior-posterior polarity, to gastrulation, when the germ cells are set aside and the three primary germ layers are specified. Relevant studies in lower vertebrates indicate the conservation and divergence of regulatory mechanisms for cell lineage allocation and axis patterning.


An evaluative study of a community health service development.
This paper describes a research study designed to evaluate a community health service development in one health authority in rural England. The study compared two types of primary care teams working towards the same objectives. Surveys of patients and staff in the health authority were conducted about a range of issues, defined by the original aims of the scheme. Measures were made of care received by people over 75 years of age, consumer satisfaction, staff experiences of the multi-disciplinary team, job satisfaction and liaison with social services personnel. Few differences existed between the two forms of care on all of these measures. This paper contains a discussion of the findings alongside an examination of the implications for future health service developments, particularly flagship enterprises such as nursing development units. The importance of well established baseline measurements is emphasized by both the research findings and the discussion.


Association Between Bedroom Particulate Matter Filtration and Changes in Airway Pathophysiology in Children With Asthma.
Fine particles (particulate matter 2.5 μm [PM2.5]), a ubiquitous air pollutant, can deposit in the small airways that play a vital role in asthma. It appears to be unknown whether the use of a PM2.5 filtration device can improve small airway physiology and respiratory inflammation in children with asthma. To discover what pathophysiological changes in the small airways are associated with using a PM2.5-removing device in the bedrooms of children with asthma. Children with mild or moderate asthma were enrolled in this double-blind, crossover study. The participants used a true filtration device and a sham filtration device in their bedrooms in a random order for 2 weeks each with a 2-week washout interval. The study was conducted in a suburb of Shanghai, China, during a low-ozone season. Ozone and PM2.5 were measured inside bedrooms and outside a window. Impulse oscillometry, spirometry, and fractional exhaled nitric oxide were measured at the beginning and the end of each intervention. Peak expiratory flow was measured twice daily at home. Forty-three children (5-13 years old; 26 boys [60%]) participated. Outdoor 24-hour mean PM2.5 concentrations were moderately high, ranging from 28.6 to 69.8 μg/m3 (median, 53 μg/m3). During true filtration, bedroom PM2.5 concentrations were a mean (SD) of 63.4% (35.9%) lower than during sham filtration. Compared with sham filtration, true filtration was significantly associated with improved airway mechanics, reflected in a 24.4% (95% CI, 11.8%-37.1%) reduction in total airway resistance, a 43.5% (95% CI, 13.7%-73.3%) reduction in small airway resistance, a 22.2% (95% CI, 2.2%-42.2%) reduction in resonant frequency, and a 73.1% (95% CI, 0.3%-145.8%) increase in airway reactance. True filtration was also associated with significant improvements in fractional exhaled nitric oxide (a 27.6% [95% CI, 8.9%-42.4%] reduction) and peak expiratory flow (a 1.6% [95% CI, 0.8%-2.5%] increase). These improvements were significantly associated with bedroom PM2.5 reduction. Improvements in small airway function were nonsignificant (8.4% [95% CI, -1.4% to 18.3%]) in all participants but significant (13.2% [95% CI, 1.2%-25.1%]) in participants without eosinophilic airway inflammation at baseline. No improvements were observed for forced vital capacity, forced expiratory volume during the first second, and the ratio of these in all participants or subgroups. Per these results, indoor PM2.5 filtration can be a practical method to improve air flow in an asthmatic lung through improved airway mechanics and function as well as reduced inflammation. This warrants a clinical trial to confirm. ClinicalTrials.gov Identifier: NCT03282864.


Women's experiences of appearance concern and body control across the lifespan: challenging accepted wisdom.
This study adopted a lifespan approach to women's experiences of appearance concern and body control. Thirty-two women (aged 16 to 77) were interviewed about their exercise and food regulation. Results of the grounded theory analysis challenge social constructions of appearance concern as associated principally with the reproductive years, and of the body as malleable, and highlight the complexity of the relationship between appearance concern and body control. Despite frequent persistence of (or increase in) appearance concern beyond young adulthood, 'healthier' responses to appearance concern occurred due to changing priorities and increasing awareness. Findings highlight the utility of an inclusive and qualitative approach, and the absence of simple and sovereign factors determining an individual's levels of appearance concern or body control.


RTOG sarcoma radiation oncologists reach consensus on gross tumor volume and clinical target volume on computed tomographic images for preoperative radiotherapy of primary soft tissue sarcoma of extremity in Radiation Therapy Oncology Group studies.
To develop a Radiation Therapy Oncology Group (RTOG) atlas delineating gross tumor volume (GTV) and clinical target volume (CTV) to be used for preoperative radiotherapy of primary extremity soft tissue sarcoma (STS). A consensus meeting was held during the RTOG meeting in January 2010 to reach agreement about GTV and CTV delineation on computed tomography (CT) images for preoperative radiotherapy of high-grade large extremity STS. Data were presented to address the local extension of STS. Extensive discussion ensued to develop optimal criteria for GTV and CTV delineation on CT images. A consensus was reached on appropriate CT-based GTV and CTV. The GTV is gross tumor defined by T1 contrast-enhanced magnetic resonance images. Fusion of magnetic resonance and images is recommended to delineate the GTV. The CTV for high-grade large STS typically includes the GTV plus 3-cm margins in the longitudinal directions. If this causes the field to extend beyond the compartment, the field can be shortened to include the end of a compartment. The radial margin from the lesion should be 1.5 cm, including any portion of the tumor not confined by an intact fascial barrier, bone, or skin surface. The consensus on GTV and CTV for preoperative radiotherapy of high-grade large extremity STS is available as web-based images and in a descriptive format through the RTOG. This is expected to improve target volume consistency and allow for rigorous evaluation of the benefits and risks of such treatment.


The plastidial pentose phosphate pathway is essential for postglobular embryo development in Arabidopsis.
Large numbers of genes essential for embryogenesis in Arabidopsis encode enzymes of plastidial metabolism. Disruption of many of these genes results in embryo arrest at the globular stage of development. However, the cause of lethality is obscure. We examined the role of the plastidial oxidative pentose phosphate pathway (OPPP) in embryo development. In nonphotosynthetic plastids the OPPP produces reductant and metabolic intermediates for central biosynthetic processes. Embryos with defects in various steps in the oxidative part of the OPPP had cell division defects and arrested at the globular stage, revealing an absolute requirement for the production via these steps of ribulose-5-phosphate. In the nonoxidative part of the OPPP, ribulose-5-phosphate is converted to ribose-5-phosphate (R5P)-required for purine nucleotide and histidine synthesis-and subsequently to erythrose-4-phosphate, which is required for synthesis of aromatic amino acids. We show that embryo development through the globular stage specifically requires synthesis of R5P rather than erythrose-4-phosphate. Either a failure to convert ribulose-5-phosphate to R5P or a block in purine nucleotide biosynthesis beyond R5P perturbs normal patterning of the embryo, disrupts endosperm development, and causes early developmental arrest. We suggest that seed abortion in mutants unable to synthesize R5P via the oxidative part of the OPPP stems from a lack of substrate for synthesis of purine nucleotides, and hence nucleic acids. Our results show that the plastidial OPPP is essential for normal developmental progression as well as for growth in the embryo.


[Various aspects of evolution of Alu repeats in mammals].
A complex study on various evolutionary peculiarities of the mammalia dispersed Alu repeats (Alu repeats of primates and B1 of rodents) has been carried out by phylogenetic analysis. A phylogenetic tree, containing the 7SL RNA genes and the Alu repeats of primates and rodents has been constructed. It has been shown that the branch of the phyletic line leading to the Alu repeats of primates and B1 of rodents from the 7SL RNA genes occurred after the divergence of the 7SL RNA genes of amphibia and mammalia, but before the divergence of the 7SL RNA genes of primates and rodents (250.10 years ago). A statistically reliable slowing down in the evolutionary rates of one of two monomers for the human Alu repeats has been proved. It may be caused by the functional load of the corresponding monomer in connection with the presence of a definit regulatory site in it.


Molecular dynamics simulations of Zika virus NS3 helicase: Insights into RNA binding site activity.
America is still suffering with the outbreak of Zika virus (ZIKV) infection. Congenital ZIKV syndrome has already caused a public health emergency of international concern. However, there are still no vaccines to prevent or drugs to treat the infection caused by ZIKV. The ZIKV NS3 helicase (NS3h) protein is a promising target for drug discovery due to its essential role in viral genome replication. NS3h unwinds the viral RNA to enable the replication of the viral genome by the NS5 protein. NS3h contains two important binding sites: the NTPase binding site and the RNA binding site. Here, we used molecular dynamics (MD) simulations to study the molecular behavior of ZIKV NS3h in the presence and absence of ssRNA and the potential implications for NS3h activity and inhibition. Although there is conformational variability and poor electron densities of the RNA binding loop in various apo flaviviruses NS3h crystallographic structures, the MD trajectories of NS3h-ssRNA demonstrated that the RNA binding loop becomes more stable when NS3h is occupied by RNA. Our results suggest that the presence of RNA generates important interactions with the RNA binding loop, and these interactions stabilize the loop sufficiently that it remains in a closed conformation. This closed conformation likely keeps the ssRNA bound to the protein for a sufficient duration to enable the unwinding/replication activities of NS3h to occur. In addition, conformational changes of this RNA binding loop can change the nature and location of the optimal ligand binding site, according to ligand binding site prediction results. These are important findings to help guide the design and discovery of new inhibitors of NS3h as promising compounds to treat the ZIKV infection.


Synthesis and fast transfer of monolayer MoS2 on reusable fused silica.
Atomically thin, two-dimensional materials ranging from superconductors, metals, semiconductors to insulators are emerging as potential candidates for the next-generation digital electronics and optoelectronic applications. Their synthesis on a commonly used substrate and fast transfer to a plenty of desired substrates need to be addressed to meet the industrialization criteria for practical applications. In this study, fused silica, which is amorphous, transparent, and inexpensive, was examined as a substrate for MoS2 synthesis. The MoS2 growth behavior on fused silica and its crystal quality were evaluated. In addition, a novel way was developed to quickly peel off MoS2 from the fused silica surface within 15 s (i.e., etching in an acidic solution to detach the edge and completing the delamination via a capillary force at the interface between air and water). The fused silica could be reused at least three times. Moreover, the produced MoS2 domains showed no obvious degradation of quality. These results support the feasibility of MoS2 synthesis on amorphous and recyclable substrates and also the time-saving transfer for the cost-effective and high-quality production of other two-dimensional materials.


Diversity in autoimmunity against retinal, neuronal, and axonal antigens in acquired neuro-retinopathy.
Autoimmune retinopathies and optic neuropathies are complex disorders of the retina and the optic nerve, in which patients develop autoantibodies (AAbs) against retinal and optic nerve proteins. Autoimmunity might significantly influence the outcome of retinal and optic nerve degenerative process but the pathogenic process is not fully elucidated. To better understand the role of AAbs in pathogenicity of these suspected autoimmune visual disorders, we focused on unique AAbs specificities associated with the syndrome to identify their antigenic targets in the optic nerve and retina. Serum samples were obtained from patients, whose visual disorders were potentially autoimmune in nature, including patients with cancer with possible paraneoplastic syndrome. Autoantibodies were tested against human optic nerve and retinal antigens for specificity by Western blotting and immunofluorescence. Out of 209 tested for anti-optic nerve autoantibodies, 55% showed specific neuronal autoantibodies. The repertoire of anti-optic nerve autoantibodies often differed from anti-retinal antibodies. The major antigenic targets for these antibodies could be divided into four groups. Autoantibodies specific to classical glycolytic enzymes involved in energy production (α and γ enolases, glyceraldehyde 3-phosphate dehydrogenase) also reacted with retinal antigens. Autoantibodies targeted neuronal-specific myelin proteins (MBP, MOG), aquaporin 4, and collapsing response mediator protein 5 reacted with optic nerve antigens. They showed immunostaining of axons and myelin in the optic nerve as determined by double immunofluorescence. We identified novel neuronal autoantigens not previously known to be associated with acquired autoimmune retinopathy and optic neuropathy. Knowledge of the full autoantibody repertoire perpetuating this syndrome is an important first requirement in increasing our understanding of the autoimmune process to facilitate better diagnosis, prognosis, and treatment.


Directional sensitivity of dynamic cerebral autoregulation in squat-stand maneuvers.
Dynamic cerebral autoregulation (CA), the transient response of cerebral blood flow (CBF) to rapid changes in arterial blood pressure (BP), is usually modeled as a linear mechanism. We tested the hypothesis that dynamic CA can display nonlinear behavior resulting from differential efficiency dependent on the direction of BP changes. Cerebral blood velocity (CBV) (transcranial Doppler), heart rate (HR) (three-lead ECG), continuous BP (Finometer), and end-tidal CO2 (capnograph) were measured in 10 healthy young subjects during 15 squat-stand maneuvers (SSM) with a frequency of 0.05 Hz. The protocol was repeated with a median (interquartile range) of 44 (35-64) days apart. Dynamic CA was assessed with the autoregulation index (ARI) obtained from CBV step responses estimated with an autoregressive moving-average model. Mean BP, HR, and CBV were different (all P < 0.001) between squat and stand, regardless of visits. ARI showed a strong interaction ( P < 0.001) of SSM with the progression of transients; in general, the mean ARI was higher for the squat phase compared with standing. The changes in ARI were partially explained by concomitant changes in CBV ( P = 0.023) and pulse pressure ( P < 0.001), but there was no evidence that ARI differed between visits ( P = 0.277). These results demonstrate that dynamic CA is dependent on the direction of BP change, but further work is needed to confirm if this finding can be generalized to other physiological conditions and also to assess its dependency on age, sex and pathology.


Carbon dioxide sensing in an obligate insect-fungus symbiosis: CO2 preferences of leaf-cutting ants to rear their mutualistic fungus.
Defense against biotic or abiotic stresses is one of the benefits of living in symbiosis. Leaf-cutting ants, which live in an obligate mutualism with a fungus, attenuate thermal and desiccation stress of their partner through behavioral responses, by choosing suitable places for fungus-rearing across the soil profile. The underground environment also presents hypoxic (low oxygen) and hypercapnic (high carbon dioxide) conditions, which can negatively influence the symbiont. Here, we investigated whether workers of the leaf-cutting ant Acromyrmex lundii use the CO2 concentration as an orientation cue when selecting a place to locate their fungus garden, and whether they show preferences for specific CO2 concentrations. We also evaluated whether levels preferred by workers for fungus-rearing differ from those selected for themselves. In the laboratory, CO2 preferences were assessed in binary choices between chambers with different CO2 concentrations, by quantifying number of workers in each chamber and amount of relocated fungus. Leaf-cutting ants used the CO2 concentration as a spatial cue when selecting places for fungus-rearing. A. lundii preferred intermediate CO2 levels, between 1 and 3%, as they would encounter at soil depths where their nest chambers are located. In addition, workers avoided both atmospheric and high CO2 levels as they would occur outside the nest and at deeper soil layers, respectively. In order to prevent fungus desiccation, however, workers relocated fungus to high CO2 levels, which were otherwise avoided. Workers' CO2 preferences for themselves showed no clear-cut pattern. We suggest that workers avoid both atmospheric and high CO2 concentrations not because they are detrimental for themselves, but because of their consequences for the symbiotic partner. Whether the preferred CO2 concentrations are beneficial for symbiont growth remains to be investigated, as well as whether the observed preferences for fungus-rearing influences the ants' decisions where to excavate new chambers across the soil profile.


Dental plaque, preventive care, and tooth brushing associated with dental caries in primary teeth in schoolchildren ages 6-9 years of Leon, Nicaragua.
Our study aimed to evaluate the effect of various risk indicators for dental caries on primary teeth of Nicaraguan children (from Leon, Nicaragua) ages 6 to 9, using the negative binomial regression model. A cross-sectional study was carried out to collect clinical, demographic, socioeconomic, and behavioral data from 794 schoolchildren ages 6 to 9 years, randomly selected from 25 schools in the city of León, Nicaragua. Clinical examinations for dental caries (dmft index) were performed by 2 trained and standardized examiners. Socio-demographic, socioeconomic, and behavioral data were self-reported using questionnaires. Multivariate negative binomial regression (NBR) analysis was used. Mean age was 7.49 ± 1.12 years. Boys accounted for 50.1% of the sample. Mean dmft was 3.54 ± 3.13 and caries prevalence (dmft >0) was 77.6%. In the NBR multivariate model (p<0.05), for each year of age, the expected mean dmft decreased by 7.5%. Brushing teeth at least once a day and having received preventive dental care in the last year before data collection were associated with declines in the expected mean dmft by 19.5% and 69.6%, respectively. Presence of dental plaque increased the expected mean dmft by 395.5%. The proportion of students with caries in this sample was high. We found associations between dental caries in the primary dentition and dental plaque, brushing teeth at least once a day, and having received preventive dental care. To improve oral health, school programs and/or age-appropriate interventions need to be developed based on the specific profile of caries experience and the associated risk indicators.


Periodic population codes: From a single circular variable to higher dimensions, multiple nested scales, and conceptual spaces.
Across the nervous system, neurons often encode circular stimuli using tuning curves that are not sine or cosine functions, but that belong to the richer class of von Mises functions, which are periodic variants of Gaussians. For a population of neurons encoding a single circular variable with such canonical tuning curves, computing a simple population vector is the optimal read-out of the most likely stimulus. We argue that the advantages of population vector read-outs are so compelling that even the neural representation of the outside world's flat Euclidean geometry is curled up into a torus (a circle times a circle), creating the hexagonal activity patterns of mammalian grid cells. Here, the circular scale is not set a priori, so the nervous system can use multiple scales and gain fields to overcome the ambiguity inherent in periodic representations of linear variables. We review the experimental evidence for this framework and discuss its testable predictions and generalizations to more abstract grid-like neural representations.


Mitral atresia. Morphological details.
The morphological characteristics of mitral atresia were studied in 30 hearts to determine the presence or absence of a morphological rudiment of the atretic valve and the relation of this rudiment, if found, to any chamber in the ventricular mass. All the hearts showed atrial situs solitus and no ventricular inversion; consequently all had left atrioventricular atresia. In all instances dense fibrous tissue connected the floor of the left atrium to the left ventricle. This connective tissue is considered to be the morphological rudiment of the atretic mitral valve. In several hearts the intervening fibrous tissue varied from a thick fibrous membrane to a tiny fibrous cord; it is impossible to detect these variations clinically. It is, therefore, more practical to classify those hearts which have a detectable fibrous membrane macroscopically as having an "imperforate membrane" and those with a fibrous strand detectable only microscopically as having an "absent atrioventricular connection."


Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.
Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) programme that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.


Rampant exchange of the structure and function of extramembrane domains between membrane and water soluble proteins.
Of the membrane proteins of known structure, we found that a remarkable 67% of the water soluble domains are structurally similar to water soluble proteins of known structure. Moreover, 41% of known water soluble protein structures share a domain with an already known membrane protein structure. We also found that functional residues are frequently conserved between extramembrane domains of membrane and soluble proteins that share structural similarity. These results suggest membrane and soluble proteins readily exchange domains and their attendant functionalities. The exchanges between membrane and soluble proteins are particularly frequent in eukaryotes, indicating that this is an important mechanism for increasing functional complexity. The high level of structural overlap between the two classes of proteins provides an opportunity to employ the extensive information on soluble proteins to illuminate membrane protein structure and function, for which much less is known. To this end, we employed structure guided sequence alignment to elucidate the functions of membrane proteins in the human genome. Our results bridge the gap of fold space between membrane and water soluble proteins and provide a resource for the prediction of membrane protein function. A database of predicted structural and functional relationships for proteins in the human genome is provided at sbi.postech.ac.kr/emdmp.


Human Factors and Data Logging Processes With the Use of Advanced Technology for Adults With Type 1 Diabetes: Systematic Integrative Review.
People with type 1 diabetes (T1D) undertake self-management to prevent short and long-term complications. Advanced technology potentially supports such activities but requires consideration of psychological and behavioral constructs and usability issues. Economic factors and health care provider capacity influence access and uptake of advanced technology. Previous reviews have focused upon clinical outcomes or were descriptive or have synthesized studies on adults with those on children and young people where human factors are different. This review described and examined the relationship between human factors and adherence with technology for data logging processes in adults with T1D. A systematic literature search was undertaken by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality appraisal was undertaken and data were abstracted and categorized into the themes that underpinned the human factor constructs that were examined. A total of 18 studies were included. A total of 6 constructs emerged from the data analysis: the relationship between adherence to data logging and measurable outcomes; satisfaction with the transition to advanced technology for self-management; use of advanced technology and time spent on diabetes-related activities; strategies to mediate the complexities of diabetes and the use of advanced technology; cognition in the wild; and meanings, views, and perspectives from the users of technology. Increased treatment satisfaction was found on transition from traditional to advanced technology use-insulin pump and continuous glucose monitoring (CGM); the most significant factor was when blood glucose levels were consistently <7.00 mmol/L (P ≤.01). Participants spent considerable time on their diabetes self-care. Logging of data was positively correlated with increasing age when using an app that provided meaningful feedback (regression coefficient=55.8 recordings/year; P ≤.01). There were benefits of CGM for older people in mediating complexities and fears of hypoglycemia with significant differences in well-being (P ≤.001). Qualitative studies explored the contextual use and uptake of technology. The results suggested frustrations with CGM, continuous subcutaneous insulin infusion, calibration of devices, and alarms. Furthermore implications for "body image" and the way in which "significant others" impacted on the behavior and attitude of the individual toward technology use. There were wide variations in the normal use of and interaction with technology across a continuum of sociocultural contexts, which has implications for the way in which future technologies should be designed. Quantitative studies were limited by small sample sizes, making it difficult to generalize findings to other contexts. This was further limited by a sample that was predominantly white, well-controlled, and engaged with self-care. The use of critical appraisal frameworks demonstrated where research into human factors and data logging processes of individuals could be improved. This included engaging people in the design of the technology, especially hard-to-reach or marginalized groups.