The Management of Schizophrenia in Clinical Practice (MOSAIC) Registry: a focus on patients, caregivers, illness severity, functional status, disease burden and healthcare utilization.
The Management of Schizophrenia in Clinical Practice (MOSAIC), a disease-based registry of schizophrenia, was initiated in December 2012 to address important gaps in our understanding of the impact and burden of schizophrenia and to provide insight into the current status of schizophrenia care in the US. Recruitment began in December 2012 with ongoing assessment continuing through May 2014. Participants were recruited from a network of 15 centralized Patient Assessment Centers supporting proximal care sites. Broad entry criteria included patients diagnosed with schizophrenia, schizophreniform or schizoaffective disorder, presenting within the normal course of care, in usual treatment settings, aged ≥18years and able to read and speak English. By May 2014, 550 participants (65.8% male, 59.8% White, 64.4% single, mean age 42.9years), were enrolled. The majority had a diagnosis of schizophrenia (62.0%). Mean illness duration at entry was 15.0years. Common comorbidities at entry were high lipid levels (26.9%), hypertension (23.1%) and type II diabetes (13%). Participants were categorized by baseline overall Clinical Global Impression-Schizophrenia Severity Score as minimally (9.1%), mildly (25.3%), moderately (39.9%), markedly (22.3%) and severely (3.4%) ill. Most commonly used second generation antipsychotics at entry were risperidone (17.8%), clozapine (16.5%), olanzapine (14.0%), aripiprazole (13.6%) and quetiapine (5.6%). No large-scale patient registry has been conducted in the US to longitudinally follow patients with schizophrenia and describe symptom attributes, support network, care access and disease burden. These data provide important epidemiological, clinical and outcome insights into the burden of schizophrenia in the US.


Composite reflective/absorptive IR-blocking filters embedded in metamaterial antireflection-coated silicon.
Infrared (IR)-blocking filters are crucial for controlling the radiative loading on cryogenic systems and for optimizing the sensitivity of bolometric detectors in the far-IR. We present a new IR filter approach based on a combination of patterned frequency-selective structures on silicon and a thin (25-75 μm thick) absorptive composite based on powdered reststrahlen absorbing materials. For a 300 K blackbody, this combination reflects ∼50% of the incoming light and blocks >99.8% of the total power with negligible thermal gradients and excellent low-frequency transmission. This allows a reduction in the IR thermal loading to negligible levels in a single cold filter. These composite filters are fabricated on silicon substrates, which provide excellent thermal transport laterally through the filter and ensure that the entire area of the absorptive filter stays near the bath temperature. A metamaterial antireflection coating cut into these substrates reduces in-band reflections to below 1%, and the in-band absorption of the powder mix is below 1% for signal bands below 750 GHz. This type of filter can be directly incorporated into silicon refractive optical elements.


Microbial colonization and controls in dryland systems.
Drylands constitute the most extensive terrestrial biome, covering more than one-third of the Earth's continental surface. In these environments, stress limits animal and plant life, so life forms that can survive desiccation and then resume growth following subsequent wetting assume the foremost role in ecosystem processes. In this Review, we describe how these organisms assemble in unique soil- and rock-surface communities to form a thin veneer of mostly microbial biomass across hot and cold deserts. These communities mediate inputs and outputs of gases, nutrients and water from desert surfaces, as well as regulating weathering, soil stability, and hydrological and nutrient cycles. The magnitude of regional and global desert-related environmental impacts is affected by these surface communities; here, we also discuss the challenges for incorporating the consideration of these communities and their effects into the management of dryland resources.


Detection and characterization of usability problems in structured data entry interfaces in dentistry.
Poor usability is one of the major barriers for optimally using electronic health records (EHRs). Dentists are increasingly adopting EHRs, and are using structured data entry interfaces to enter data such that the data can be easily retrieved and exchanged. Until recently, dentists have lacked a standardized terminology to consistently represent oral health diagnoses. In this study we evaluated the usability of a widely used EHR interface that allow the entry of diagnostic terms, using multi-faceted methods to identify problems and work with the vendor to correct them using an iterative design method. Fieldwork was undertaken at two clinical sites, and dental providers as subjects participated in user testing (n=32), interviews (n=36) and observations (n=24). User testing revealed that only 22-41% of users were able to successfully complete a simple task of entering one diagnosis, while no user was able to complete a more complex task. We identified and characterized 24 high-level usability problems reducing efficiency and causing user errors. Interface-related problems included unexpected approaches for displaying diagnosis, lack of visibility, and inconsistent use of UI widgets. Terminology related issues included missing and mis-categorized concepts. Work domain issues involved both absent and superfluous functions. In collaboration with the vendor, each usability problem was prioritized and a timeline set to resolve the concerns. Mixed methods evaluations identified a number of critical usability issues relating to the user interface, underlying terminology of the work domain. The usability challenges were found to prevent most users from successfully completing the tasks. Our further work we will determine if changes to the interface, terminology and work domain do result in improved usability.


AKINbeta3, a plant specific SnRK1 protein, is lacking domains present in yeast and mammals non-catalytic beta-subunits.
The SNF1/AMPK/SnRK1 heterotrimeric kinase complex is involved in the adaptation of cellular metabolism in response to diverse stresses in yeast, mammals and plants. Following a model proposed in yeast, the kinase targets are likely to bind the complex via the non-catalytic beta-subunits. These proteins currently identified in yeast, mammals and plants present a common structure with two conserved interacting domains named Kinase Interacting Sequence (KIS) and Association with SNF1 Complex (ASC), and a highly variable N-terminal domain. In this paper we describe the characterisation of AKINbeta3, a novel protein related to AKINbeta subunits of Arabidopsis thaliana, containing a truncated KIS domain and no N-terminal extension. Interestingly the missing region of the KIS domain corresponds to the glycogen-binding domain (beta-GBD) identified in the mammalian AMPKbeta1. In spite of its unusual features, AKINbeta3 complements the yeast sip1Deltasip2Deltagal83Delta mutant. Moreover, interactions between AKINbeta3 and other AKIN complex subunits from A. thaliana were detected by two-hybrid experiments and in vitro binding assays. Taken together these data demonstrate that AKINbeta3 is a beta-type subunit. A search for beta-type subunits revealed the existence of beta3-type proteins in other plant species. Furthermore, we suggest that the AKINbeta3-type subunits could be plant specific since no related sequences have been found in any of the other completely sequenced genomes. These data suggest the existence of novel SnRK1 complexes including AKINbeta3-type subunits, involved in several functions among which some could be plant specific.


Effect of oscillation on elevating shear stresses.
The effect of oscillation on elevating turbulent shear stresses through the Jellyfish and St. Vincent valves has been investigated. Laser Doppler anemometry was employed to determine the velocity and shear stress distributions at various locations downstream of the valves. Comparison between two valves revealed that at 0.5D downstream of the valves the magnitude of shear stresses in the Jellyfish valve were much higher than those of the St. Vincent valve at cardiac outputs of 4, 5.5 and 7 l min(-1). The cause of high shear stresses in close proximity to the Jellyfish valve could be attributed to the oscillation of the membrane which in turn generated a wake downstream of the valve (in the core of valve chamber) and produced a wide region of disturbance further downstream. This resulted in further pressure drag, and consequently higher pressure drops across the valve and higher shear stresses downstream of the valve.


Is excessive running predictive of degenerative hip disease? Controlled study of former elite athletes.
To determine the effects of regular long distance running on the state of the hips in later life. Retrospective study of a cohort of elite athletes and a group of normal, healthy, untrained controls examined 15 years after initial testing. Research project at school for physical education and sports. 27 Former long distance runners (mean age 42), nine former bobsleigh riders (mean age 42), and 23 normal, healthy, untrained men (mean age 35) who had been examined in 1973 and who agreed to re-examination in 1988. Radiological evidence of degenerative hip disease in 1988. Physiological and exercise characteristics of all subjects had been recorded in 1973, and in 1988 these measurements were repeated together with radiological examination of the hips. An additive radiological index of hip disease based on grades of subchondral sclerosis, osteophyte formation, and joint space narrowing was significantly increased among runners as compared with bobsleigh riders and untrained controls. After adjustment for age the significant effect of type of sports activity remained (p = 0.032). In multivariate analyses age and milage run in 1973 (97 km/week) emerged as independent, significant, and positive predictors of radiological signs of degenerative hip disease in 1988 (p = 0.017 and p = 0.024 respectively). Among runners alone running pace in 1973 rather than milage run was the stronger predictor of subsequent degenerative hip disease. The milage run in 1988 was not particularly predictive of the radiological index, but endurance in 1988 was inversely related to degenerative hip disease seen radiologically. Long term, high intensity, high milage running should not be dismissed as a potential risk factor for premature osteoarthritis of the hip.


Attitudes, health lifestyle behaviors and cardiometabolic risk factors among relatives of individuals with type 2 diabetes mellitus.
To describe and compare attitudes, lifestyle behaviors, and cardiometabolic risk factors between individuals with and without a relative with type 2 diabetes mellitus (T2DM) living in the same household. A secondary analysis of baseline data from an implementation study in Peru was conducted. The outcomes were attitudes towards changing lifestyle behaviors (e.g. intentions towards losing weight, increasing physical activity, reducing salt consumption, etc), profiles of health lifestyle behaviors (e.g. daily smoking, heavy drinking, and physical activity), and cardiometabolic risk factors (e.g., overweight [body mass index ≥25 kg/m2] and hypertension); whereas the exposure was the presence of at least one relative with known diagnosis of T2DM living in the same household. Multilevel logistic mixed effect regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 2298 records, 1134 (49.4%) males, mean age 43.3 (SD: 17.2) years, were analyzed. There was no evidence of a difference in lifestyle-changing attitudes, smoking, alcohol drinking, physical activity levels, and hypertension between individuals with and without relatives with T2DM. Overweight was 63% more common among individuals having a relative with a T2DM in multivariable model (OR = 1.63; 95% CI: 1.03-2.61). Individuals with relatives with T2DM have higher probabilities of being overweight compared to those who did not have relatives with T2DM in the same household. The absence of differences on lifestyle-related attitudes and behaviors highlight the need of involving relatives of patients with T2DM on intervention strategies to further enhance diabetes prevention and management efforts.


High-Q hybrid 3D-2D slab-3D photonic crystal microcavity.
The radiation loss in the escaping light cone with a two-dimensional (2D) photonic crystal slab microcavity can be suppressed by means of cladding the low-Q slab microcavity by three-dimensional woodpile photonic crystals with the complete bandgap when the resonance frequency is located inside the complete bandgap. It is confirmed that the hybrid microcavity based on a low-Q, single-defect photonic crystal slab microcavity shows improvement of the Q factor without affecting the mode volume and modal frequency. Whereas 2D slab microcavities exhibit Q saturation with an increase in the number of layers, for the analyzed hybrid microcavities with a small gap between the slab and woodpiles, the Q factor does not saturate.


Continuously tunable slow-light device consisting of heater-controlled silicon microring array.
We experimentally demonstrate a tunable slow-light device consisting of all-pass Si microrings. A compact device of 0.014 mm2 footprint is fabricated by using CMOS-compatible process, and its center wavelength, bandwidth and delay are continuously tuned by integrated heaters. The tuning range is 300 ps at fixed wavelengths with a 1 nm bandwidth. Eye opening of 40 Gbps non-return-to-zero signals is observed at up to a 150 ps delay and a 4 bit buffering capacity is confirmed, which corresponds to a spatial buffering density of 0.29 kbit/mm2.


"Just because you're pregnant, doesn't mean you're sick!" A qualitative study of beliefs regarding physical activity in black South African women.
Despite the benefits of physical activity during pregnancy, the physiological and psychological changes that occur during this unique period may put women at greater risk of being sedentary. Lifestyle and environmental transitions have left black South African women at increased risk of physical inactivity and associated health risks. Therefore, the aim of this qualitative study was to describe the beliefs regarding physical activity during pregnancy in an urban African population. Semi-structured interviews (n = 13) were conducted with pregnant black African women during their third trimester. Deductive thematic analysis was completed based on the Theory of Planned Behaviour. Coding and analysis was completed with the assistance of ATLAS.ti software. Participants had a mean age of 28 (19-41) years, and a mean BMI of 30 (19.6-39.0) kg/m(2). Although the majority of women believed that physical activity was beneficial, this did not appear to translate into behaviour. Reported reasons for this included barriers such as pregnancy-related discomforts, lack of time, money and physical activity related education, all of which can contribute to a reduced perceived control to become active. Opportunities to participate in group exercise classes was a commonly reported facilitator for becoming active. In addition, influential role players, such as family, friends and healthcare providers, as well as cultural beliefs, reportedly provided the women with vague, conflicting and often discouraging advice about physical activity during pregnancy. This study provides new theoretical insight on the beliefs of urban South African pregnant women regarding physical activity. Findings from this study suggest a holistic approach to improve physical activity compliance during pregnancy, inclusive of physical activity education and exercise opportunities within a community setting. This study presents critical formative work upon which contextually and culturally sensitive interventions can be developed.


Comprehensive analysis of proton range uncertainties related to stopping-power-ratio estimation using dual-energy CT imaging.
The dual-energy CT-based (DECT) approach holds promise in reducing the overall uncertainty in proton stopping-power-ratio (SPR) estimation as compared to the conventional stoichiometric calibration approach. The objective of this study was to analyze the factors contributing to uncertainty in SPR estimation using the DECT-based approach and to derive a comprehensive estimate of the range uncertainty associated with SPR estimation in treatment planning. Two state-of-the-art DECT-based methods were selected and implemented on a Siemens SOMATOM Force DECT scanner. The uncertainties were first divided into five independent categories. The uncertainty associated with each category was estimated for lung, soft and bone tissues separately. A single composite uncertainty estimate was eventually determined for three tumor sites (lung, prostate and head-and-neck) by weighting the relative proportion of each tissue group for that specific site. The uncertainties associated with the two selected DECT methods were found to be similar, therefore the following results applied to both methods. The overall uncertainty (1σ) in SPR estimation with the DECT-based approach was estimated to be 3.8%, 1.2% and 2.0% for lung, soft and bone tissues, respectively. The dominant factor contributing to uncertainty in the DECT approach was the imaging uncertainties, followed by the DECT modeling uncertainties. Our study showed that the DECT approach can reduce the overall range uncertainty to approximately 2.2% (2σ) in clinical scenarios, in contrast to the previously reported 1%.


ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia.
In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6-1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a 'black box' warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.


Sexual behaviors, condom use, and sexual health of Americans over 50: implications for sexual health promotion for older adults.
In the contemporary U.S., men and women are living longer and healthier lives. As such, many people spend greater portions of their lives as sexually active individuals. Yet, little is known about the myriad of ways that older adults experience their sexual lives. This study sought to assess the context and frequency of sexual behaviors, condom use, sexual pleasure, and sexual experience of men and women over age 50. Information regarding the sexual experiences of a nationally representative sample of men and women over age 50 within the past year was examined. Sexual behavior over the past year was assessed in relation to several situational and contextual characteristics (e.g., event location, type of partner, health status, condom use). Participants were also asked about their experience (i.e., pleasure, arousal, pain, lubrication/erectile difficulties, and orgasm) during their most recent partnered sexual event. Bivariate or ordinal logistic regression models were used to investigate the relationship of age, health and partner status to sexual frequency and experience. Although sizable proportions (20-30%) of both men and women remained sexually active well into their 80s age was related to a lower likelihood of solo and most partnered sexual behaviors. When controlling for age, relationship status, and health remained significant predictors of select sexual behaviors. The participant's evaluation of their most recent sexual experience in terms of arousal, erectile difficulty, and orgasm all declined with age. Health status was related to men's evaluation of the experience. Relationship status was the most consistent predictor of women's evaluation of the experience. Condom use rates remained low for participants across age groups. Many older adults continue be sexually active well into advanced age (80+). Thus, providers need to be attentive to the diverse sexual health needs of older adults.


Characteristics of canine lower esophageal sphincter: a new electrophysiological tool.
The canine lower esophageal sphincter (LES) was evaluated as a model for investigation of the electrophysiology of nonadrenergic noncholinergic neurotransmission. The LES contained a dense collection of gap junctions and a moderate number of nerves located at the periphery of muscle bundles, which are often associated with interstitial cells of Cajal. These cells make gap junctions with one another and with smooth muscle cells. The nerve varicosities contained many large dense cored vesicles. In vitro the LES produced spontaneous active tone and relaxed to field stimulation that was blocked by tetrodotoxin (TTX). Increase of stimulus duration or frequency produced a partially TTX-insensitive sphincter relaxation. Basal tone and nerve-mediated relaxation were unaffected by cholinergic, histaminergic, or adrenergic antagonists. Acetylcholine, carbachol, or histamine caused TTX-insensitive contractions mediated by M2- and H1-receptors, respectively. Vasoactive intestinal peptide (10(-6) M) and isoproterenol (10(-6) M) relaxed the LES to the same extent as field stimulation. In the double sucrose gap this tissue regularly produced inhibitory junction potentials when field stimulated. The canine LES has appropriate morphological and pharmacological properties for the electrophysiological study of nonadrenergic noncholinergic neural responses, their mechanisms, and mediators.


Microbial growth yield estimates from thermodynamics and its importance for degradation of pesticides and formation of biogenic non-extractable residues.
In biodegradation studies with isotope-labelled pesticides, fractions of non-extractable residues (NER) remain, but their nature and composition is rarely known, leading to uncertainty about their risk. Microbial growth leads to incorporation of carbon into the microbial mass, resulting in biogenic NER. Formation of microbial mass can be estimated from the microbial growth yield, but experimental data is rare. Instead, we suggest using prediction methods for the theoretical yield based on thermodynamics. Recently, we presented the Microbial Turnover to Biomass (MTB) method that needs a minimum of input data. We have estimated the growth yield of 40 organic chemicals (31 pesticides) using the MTB and two existing methods. The results were compared to experimental values, and the sensitivity of the methods was assessed. The MTB method performed best for pesticides. Having the theoretical yield and using the released CO2 as a measure for microbial activity, we predicted a range for the formation of biogenic NER. For the majority of the pesticides, a considerable fraction of the NER was estimated to be biogenic. This novel approach provides a theoretical foundation applicable to the evaluation and prediction of biogenic NER formation during pesticide degradation experiments, and may also be employed for the interpretation of NER data from regulatory studies.


MRI appearance does not change in the first 7 days after acute hamstring injury-a prospective study.
The optimal timing of MRI following acute hamstring injury is not known and is mainly based on expert opinions. To describe the day-to-day changes in the extent of oedema and investigate the optimal timing for detection of fibre disruption on MRI following acute hamstring injuries. Prospective, descriptive study. We performed standardised MRI (1.5T) ≤1 day after injury in male athletes with acute hamstring injury. If initial MRI revealed positive signs of injury (increased signal intensity on fluid sensitive sequences), consecutive MRIs were obtained daily throughout the subsequent week (ie, 7 times). The MRI parameters (day 1-7) were scored by a single radiologist using a standardised scoring form. The day-to-day changes in the extent of oedema (distance from tuber, craniocaudal length, mediolateral width and anteroposterior depth) and the presence and extent of fibre disruption (tear) were assessed with descriptive statistics and repeated measures using analysis of variance of log-transformed data. The overall main effect for time was reported with a significance level set at p<0.05. 13 out of 132 male athletes assessed for eligibility between January 2014 and December 2015 were included. 1 dropped out, while 12 (31 years, range 20-49) completed the study; 11 had 7 MRI scans each and one had 5 MRI scans performed. There were no significant day-to-day changes for any of the extent of oedema measures (p values ranging from 0.12 to 0.81). Fibre disruption (tear), present in 5 of the athletes, was detectable from day 1, with small and insignificant day-to-day changes (p values ranging from 0.45 to 0.95). We observed insignificant day-to-day changes in the extent of oedema throughout the first week following acute hamstring injury. Fibre disruption (tear) was detectable from the first day after injury. These findings indicate that MRI can be performed on any day during the first week following an acute (hamstring) muscle injury.


Laser: a powerful tool for treatment of pyogenic granuloma.
Lasers have opened a new door for the treatment of various disorders. Treatment of soft tissue intraoral mucosal growth by laser has profound effect on the patient acceptability taking the functional and aesthetic factor into consideration. The patient is able to get the outdoor treatment without the phobia of local anaesthetic and is out of the clinic in few minutes in contrast to the traditional method of surgical excision. Very few cases have been reported in literature regarding treatment of mucosal growth by soft tissue lasers. We present a case of recurrent pyogenic granuloma in a patient treated with an alternative approach, that is, diode laser, without the use of anaesthesia, sutures, anti-inflammatory drugs, or analgesics. The diagnosis of this lesion is equally important for correct treatment planning.


RAPID PROGRESSION OF FOVEOMACULAR RETINOSCHISIS IN YOUNG MYOPICS.
To describe a foveomacular retinoschisis that has not been described. Patients with foveomacular retinoschisis were included. Exclusion criteria included refractive error over -6.00 diopters, presence of posterior staphyloma, positive RS1-gene mutation, family history of retinoschisis, optic disk abnormalities, or glaucoma. Vitrectomy was performed on eyes with functional or structural deterioration. Seventeen eyes from 10 patients (15-30 years old, 8 females and 2 males) with foveoschisis were recruited, with bilateral involvement in 7 patients and unilateral in 3 patients. Vitrectomy was performed in 13 eyes (13/17, 76.5%). Seven eyes (6 patients) were operated soon after the first presentation because of poor vision and severe foveoschisis. Six eyes (6 patients) were operated 2 weeks to 13 months later because of deterioration of vision and foveoschisis. Preoperative vision was 20/134 ± 20/165, and postoperative vision was 20/25 ± 20/57, with visual improvement of 6.9 (4-14) lines. The mean postoperative follow-up period was 36.5 (15-69) months. Four eyes (4 patients) were asymptomatic, despite progression of foveoschisis. Three eyes (3 patients) maintained normal macula structures. We report a foveomacular retinoschisis characterized by young age of onset, female predominant, no highly myopia, mostly bilateral involvement, and rapid progression of foveoschisis and visual acuity. Vitrectomy is effective in restoring anatomical structure and stabilize vision.


"Buruli ulcer and leprosy, they are intertwined": Patient experiences of integrated case management of skin neglected tropical diseases in Liberia.
Skin neglected tropical diseases (NTDs) such as Buruli ulcer (BU) and leprosy produce significant stigma and disability. Shared clinical presentations and needs for care present opportunities for integrated case management in co-endemic areas. As global policies are translated into local integrated services, there remains a need to monitor what new configurations of care emerge and how individuals experience them. To explore patient experiences of integrated case management for skin NTDs, in 2018, we conducted a field-based qualitative case series in a leprosy rehabilitation centre in Ganta, Liberia where BU services were recently introduced. Twenty patients with BU (n = 10) and leprosy (n = 10) participated in in-depth interviews that incorporated photography methods. We contextualised our findings with field observations and unstructured interviews with health workers. The integration of care for BU and leprosy prompted new conceptualisations of these diseases and experiences of NTD stigma. Some patients felt anxiety about using services because they feared being infected with the other disease. Other patients viewed the two diseases as 'intertwined': related manifestations of the same condition. Configurations of inter-disease stigma due to fear of transmission were buffered by joint health education sessions which also appeared to facilitate social support between patients in the facility. For both diseases, medication and wound care were viewed as the cornerstones of care and appreciated as interventions that led to rehabilitation of the whole patient group through shared experiences of healing, avoidance of physical deformities and stigma reduction. Patient accounts of intense pain during wound care for BU and inability of staff to manage severe complications, however, exposed some shortcomings of medical care for the newly integrated service, as did patient fears of long-lasting disability due to lack of physiotherapy services. Under integrated care policies, the possibility of new discourses about skin NTD identities emerging along with new configurations of stigma may have unanticipated consequences for patients' experiences of case management. The social experience of integrated medication and wound dressing has the potential to link patients within a single, supportive patient community. Control programmes with resource constraints should anticipate potential challenges of integrating care, including the need to ameliorate lasting disability and provide adequate clinical management of severe BU cases.


Cortical blood flow during extracranial-intracranial bypass surgery.
Cortical blood flow was evaluated at the time of surgery with a thermal diffusion flow probe in 25 extracranial-intracranial bypass operations. The procedures were performed 14 times for carotid occlusion, 6 times for inaccessible carotid stenosis, on 3 occasions for middle cerebral occlusion, once for basilar occlusion and once for middle cerebral stenosis. Fifty-seven different cortical regions were evaluated before and after completion of the anastomosis. During temporary occlusion of the cortical vessel, no significant changes in cortical blood flow were identified. The mean flow pre-bypass was 58 ml/100 g/min and postbypass was 66. This was a significant difference. When initial ischemic areas were evaluated, flows increased from 36 ml/100 g/min to 52 ml/100 g/min. These postbypass flows were statistically different than the flow values in the nonischemic areas of 75 ml/100 g/min. Blood pressure and arterial carbon dioxide tension did not vary significantly. Extracranial-intracranial bypass increases cortical flow in ischemic areas although this does not bring the flow into the normal range.


Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction.
Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success.


Advances in hemophagocytic lymphohistiocytosis: pathogenesis, early diagnosis/differential diagnosis, and treatment.
Hemophagocytic lymphohistiocytosis (HLH) is a histiocytic disorder characterized by a highly stimulated, but ineffective, immune response to antigens, which results in life-threatening cytokine storm and inflammatory reaction. Considerable progress has been made during the past 2 decades. Detection of molecular genetic abnormalities in genes involved in immune response pathways, such as PRF1, STX11, UNC13D, STXBP2, RAB27A, LYST, AP3B1, SH2D1A, and BIRC4, is confirmatory for the diagnosis. Clinical diagnosis is largely made according to HLH-2004 criteria. However, a new finding of the Th1/Th2 cytokine pattern (significant increase of IFN-γ and IL-10 with slightly increased or normal level of IL-6) is a useful biomarker for the early diagnosis, differential diagnosis, and the monitoring of the disease. Intensive immunosuppressive therapy is generally accepted as treatment for the relief of clinical symptoms/signs, while allogeneic hematopoietic stem cell transplantation is currently the only potentially curative therapy option for severe familial forms of HLH.


Isotope analysis of human dental calculus δ13 CO3 2- : Investigating a potential new proxy for sugar consumption.
Dental calculus (mineralised dental plaque) is composed primarily of hydroxyapatite. We hypothesise that the carbonate component of dental calculus will reflect the isotopic composition of ingested simple carbohydrates. Therefore, dental calculus carbonates may be an indicator for sugar consumption, and an alternative to bone carbonate in isotopic palaeodiet studies. We utilised Fourier transform infrared attenuated total reflectance analysis to characterise the composition and crystallisation of bone and dental calculus before isotope analysis of carbonate. Using a Sercon 20-22 mass spectrometer coupled with a Sercon GSL sample preparation system and an IsoPrime 100 dual inlet mass spectrometer plus Multiprep device to measure carbon, we tested the potential of dental calculus carbonate to identify C4 resources in diet through analysis of δ13 C values in paired bone, calculus and teeth mineral samples. The modern population shows higher δ13 C values in all three tissue carbonates compared to both archaeological populations. Clear differences in dental calculus δ13 C values are observed between the modern and archaeological individuals suggesting potential for utilising dental calculus in isotope palaeodiet studies. The offset between dental calculus and either bone or enamel carbonate δ13 C values is large and consistent in direction, with no consistent offset between the δ13 C values for the three tissues per individual. Our results support dental calculus carbonate as a new biomaterial to identify C4 sugar through isotope analysis. Greater carbon fractionation in the mouth is likely due to the complex formation of dental calculus as a mineralized biofilm, which results in consistently high δ13 C values compared to bone and enamel.


Using computer, mobile and wearable technology enhanced interventions to reduce sedentary behaviour: a systematic review and meta-analysis.
High levels of sedentary behaviour (SB) are associated with negative health consequences. Technology enhanced solutions such as mobile applications, activity monitors, prompting software, texts, emails and websites are being harnessed to reduce SB. The aim of this paper is to evaluate the effectiveness of such technology enhanced interventions aimed at reducing SB in healthy adults and to examine the behaviour change techniques (BCTs) used. Five electronic databases were searched to identify randomised-controlled trials (RCTs), published up to June 2016. Interventions using computer, mobile or wearable technologies to facilitate a reduction in SB, using a measure of sedentary time as an outcome, were eligible for inclusion. Risk of bias was assessed using the Cochrane Collaboration's tool and interventions were coded using the BCT Taxonomy (v1). Meta-analysis of 15/17 RCTs suggested that computer, mobile and wearable technology tools resulted in a mean reduction of -41.28 min per day (min/day) of sitting time (95% CI -60.99, -21.58, I2 = 77%, n = 1402), in favour of the intervention group at end point follow-up. The pooled effects showed mean reductions at short (≤ 3 months), medium (>3 to 6 months), and long-term follow-up (>6 months) of -42.42 min/day, -37.23 min/day and -1.65 min/day, respectively. Overall, 16/17 studies were deemed as having a high or unclear risk of bias, and 1/17 was judged to be at a low risk of bias. A total of 46 BCTs (14 unique) were coded for the computer, mobile and wearable components of the interventions. The most frequently coded were "prompts and cues", "self-monitoring of behaviour", "social support (unspecified)" and "goal setting (behaviour)". Interventions using computer, mobile and wearable technologies can be effective in reducing SB. Effectiveness appeared most prominent in the short-term and lessened over time. A range of BCTs have been implemented in these interventions. Future studies need to improve reporting of BCTs within interventions and address the methodological flaws identified within the review through the use of more rigorously controlled study designs with longer-term follow-ups, objective measures of SB and the incorporation of strategies to reduce attrition. The review protocol was registered with PROSPERO: CRD42016038187.


Repeated change-of-direction test for collegiate male soccer players.
The aim of the study was to investigate the applicability of a repeated change-of-direction (RCoD) test for NCAA Division-I male soccer players. The RCoD test consisted of 5 diagonal direction changes per repetition with a soccer ball to be struck at the end. Each player performed 15 repetitions with approximately 10 seconds to jog back between repetitions. Data were collected in two sessions. In the first session, 13 players were examined for heart rate responses and blood lactate concentrations. In the second session, 22 players were examined for the test's ability to discriminate the primary from secondary players (78.0±16.1 and 10.4±13.3 minutes per match, respectively). Heart rate data were available only from 9 players due to artifacts. The peak heart rate (200.2±6.6 beats∙min-1: 99.9±3.0% maximum) and blood lactate concentration (14.8±2.4 mmol∙L-1 immediately after) resulted in approximately 3.5 and 6.4-fold increases from the resting values, respectively. These values appear comparable to those during intense periods of soccer matches. In addition, the average repetition time of the test was found to discriminate the primary (4.85±0.23 s) from the secondary players (5.10±0.24 s) (P=0.02). The RCoD test appears to induce physiological responses similar to intense periods of soccer matches with respect to heart rate and blood lactate concentration. Players with better average repetition times tend to be those who play major minutes.


A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the splotch (Sp) mouse mutant.
The splotch (Sp) mouse mutant displays defects in neural tube closure in the form of exencephaly and spina bifida. Recently, mutations in the Pax-3 gene have been described in the radiation-induced Spr and Sp2H alleles. This led us to examine the integrity of the Pax-3 gene and its cellular mRNA transcript in the original, spontaneously arising Sp allele. A complex mutation in the Pax-3 gene including an A-->T transversion at the invariant 3' AG splice acceptor of intron 3 was identified in the Sp/Sp mutant. This genomic mutation abrogates the normal splicing of intron 3, resulting in the generation of four aberrantly spliced mRNA transcripts. Two of these Pax-3 transcripts make use of cryptic 3' splice sites within the downstream exon, generating small deletions which disrupt the reading frame of the transcripts. A third aberrant splicing event results in the deletion of exon 4, while a fourth retains intron 3. These aberrantly spliced mRNA transcripts are not expected to result in functional Pax-3 proteins and are thus responsible for the phenotype observed in the Sp mouse mutant.


CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity.
CAP37, an antimicrobial protein of human neutrophil granules, is a specific chemoattractant for monocytes. Purified to homogeneity by sequential chromatography over carboxymethyl Sephadex, G-75 Sephadex, and hydrophobic interaction HPLC, demonstratively endotoxin-free CAP37 was maximally chemotactic over a range of 1.3 X 10(-9)-10(-8) M. Thus it was active in the same molar concentrations as formyl-methionyl-leucyl-phenylalanine. CAP37 lacked chemotactic activity for neutrophils and lymphocytes. In checkerboard assays CAP37 had some chemokinetic activity as well. It was also chemotactic for rabbit mononuclear cells. Higher concentrations (2.7 X 10(-8) M) were required for activity with rabbit cells than with human. Sequence analysis of the first 42 NH2-terminal amino acid residues of CAP37 showed strong homologies with known serine proteases that mediate various functions in inflammation. However, a critical substitution of a serine for a histidine at position 41 suggested that CAP37 lacked serine protease action. This impression was supported by the failure of CAP37 to bind tritiated diisopropyl fluorophosphate. 89% of total CAP37 was released extracellularly from human neutrophils while they phagocytized Staphylococcus aureus. We propose that CAP37 released from neutrophils during phagocytosis and degranulation may mediate recruitment of monocytes in the second wave of inflammation.


Do UK university football club players suffer neuropsychological impairment as a consequence of their football (soccer) play?
Male players from football and rugby clubs and sportsmen from a variety of noncontact sports clubs at a UK university were compared on biographical and neuropsychological test measures. A data analysis paradigm was developed and employed to control the inflation of Type 1 error rate due to multiple hypotheses testing. Rugby players sustained most head injuries in their chosen sport, but neuropsychological tests of attention, memory, and executive function provided no evidence of performance impairment attributable to the number of head injuries sustained or the football, rugby, or noncontact sport groups. Footballers' heading frequency was related to the number of football head injuries sustained, but no relationship was detected between footballers' heading frequency and their neuropsychological test performance. Following discussion of pertinent methodological limitations it is concluded that there was no evidence in this dataset of neuropsychological impairment consistent with either mild head injury incidence or football heading frequency. However, a need for further research examining the long-term neuropsychological consequences of such head injuries was identified.


Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings.
The role of the endocannabinoid system in nicotine addiction is being increasingly acknowledged. We conducted a pilot, randomised double blind placebo controlled study set out to assess the impact of the ad-hoc use of cannabidiol (CBD) in smokers who wished to stop smoking. 24 smokers were randomised to receive an inhaler of CBD (n=12) or placebo (n=12) for one week, they were instructed to use the inhaler when they felt the urge to smoke. Over the treatment week, placebo treated smokers showed no differences in number of cigarettes smoked. In contrast, those treated with CBD significantly reduced the number of cigarettes smoked by ~40% during treatment. Results also indicated some maintenance of this effect at follow-up. These preliminary data, combined with the strong preclinical rationale for use of this compound, suggest CBD to be a potential treatment for nicotine addiction that warrants further exploration.


Evaluation of the Effects of Pinus koraiensis Needle Extracts on Serum Lipid and Oxidative Stress in Adults with Borderline Dyslipidemia: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.
Background. Dyslipidemia has been well-known as a common metabolic disorder contributing to cardiovascular disease. The aim of this study was to evaluate the effect of the Pinus koraiensis needle extracts (PKE) on the blood cholesterol and oxidative stress. Method. We conducted a 12-week randomized, double-blinded controlled trial to examine the effect of PKE on blood lipid profiles in adults with borderline dyslipidemia. Thirty-three eligible persons were recruited and randomly assigned into PKE (n = 20) and placebo groups (n = 13). Serum lipids including total cholesterol, low-density lipoprotein- (LDL-) cholesterol, high-density lipoprotein- (HDL-) cholesterol, very low-density lipoprotein- (VLDL-) cholesterol, and triglyceride were measured before and after trial. Serum insulin, glucose, and antioxidant indicators were also analyzed before and after trial and anthropometry and blood pressure were measured every 4 weeks. Results. After 12 weeks, PKE statically significant decreases in systolic blood pressure (p < 0.05) and waist circumference (p < 0.05) were observed. Also, VLDL-cholesterol significantly decreased (from 24.4 ± 10.0 mg/dL at baseline to 18.4 ± 4.1 mg/dL after 12 weeks) (p < 0.05) and superoxide dismutase (SOD) increased (6.12 ± 0.41 U/mL to 9.06 ± 0.62 U/mL) (p < 0.01) in PKE group. However, after adjustment with WC, VLDL-cholesterol was not significant between groups (p = 0.095) and while SOD remained significant between groups (p = 0.013). Conclusion. The results show that PKE was effective in improving the superoxide dismutase in the individuals with borderline dyslipidemia.


Pain and physical function are similar following axillary, muscle-sparing vs posterolateral thoracotomy.
We set out to determine whether there is a difference in postoperative pain and recovery after the patient undergoes the axillary muscle-sparing incision (ie, muscle-sparing thoracotomy [MT]) vs the modified posterolateral incision (ie, posterolateral thoracotomy [PT]). Analysis of a database originally collected to determine the effect of the timing of epidural analgesia on long-term outcome after thoracotomy. The Hospital of the University of Pennsylvania. Patients presenting for lobectomy, segmentectomy, or bilobectomy. Pain, physical activity, and the extent that pain interfered with activities following major thoracotomy were prospectively assessed with standard questionnaires (ie, the brief pain inventory and the Medical Outcomes Study 36-item short form) on postoperative days 1 to 5, and at postoperative weeks 4, 8, 12, 24, 36, and 48 by a blinded research assistant. Perioperative care was standardized and included patient-controlled thoracic epidural analgesia until thoracostomy tube removal. Eighty-two subjects underwent MT and 38 subjects underwent PT during the 16-month accrual period. There were no significant differences in demographics. Pain reported during hospitalization and after hospital discharge did not differ with respect to incision type (p > or = 0.17). Postoperative physical activity levels were significantly less than those reported preoperatively, with a trend toward better functioning in the MT groups after 8 weeks. Incision type did not predict complications, morbidity, or mortality. When comparing patients who had undergone vertical, axillary, wholly MT to those who had undergone modified serratus muscle-sparing PT, postoperative differences in pain were not apparent. One should not anticipate reduced pain or more rapid overall recovery following MT, at least when epidural analgesia is used aggressively for perioperative pain control.


The Impact of Spinal Needle Selection on Postdural Puncture Headache: A Meta-Analysis and Metaregression of Randomized Studies.
Potentially broadened indications for spinal anesthesia require increased understanding of the risk factors and prevention measures associated with postdural puncture headache (PDPH). This review is designed to examine the association between spinal needle characteristics and incidence of PDPH. Meta-analysis and metaregression was performed on randomized controlled trials to determine the effect of needle design and gauge on the incidence of PDPH after controlling for patient confounders such as age, sex, and year of publication. Fifty-seven randomized controlled trials (n = 16416) were included in our analysis, of which 32 compared pencil-point design with cutting-needle design and 25 compared individual gauges of similar design. Pencil-point design was associated with a statistically significant reduction in incidence of PDPH (risk ratio, 0.41; 95% confidence interval, 0.31-0.54; P < 0.001; I = 29%) compared with cutting needles among studies that assessed both design types. Subgroup analysis among obstetric and nonobstetric procedures yielded similar results. After adjustment for significant covariates, metaregression analysis among all 57 included trials revealed a significant correlation between needle gauge and rate of PDPH among cutting needles (slope = -2.65, P < 0.001), but not pencil-point needles (slope = -0.01, P = 0.819). Pencil-point needles are associated with significantly lower incidence of PDPH compared with the cutting-needle design. Whereas a significant relationship was noted between needle gauge and PDPH for cutting-needle design, a similar association was not shown for pencil-point needles. Providers may consider selection of larger-caliber pencil-point needle to maximize technical proficiency without expensing increased rates of PDPH.


Multicenter Comparison of Molecular Tumor Boards in The Netherlands: Definition, Composition, Methods, and Targeted Therapy Recommendations.
Molecular tumor boards (MTBs) provide rational, genomics-driven, patient-tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision-making method, reporting, and registration of the MTBs was completed through on-site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type-specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a "Dutch MTB model" for an optimal, collaborative, and nationally aligned MTB workflow. Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing.


Entrapment of Autologous von Willebrand Factor on Polystyrene/Poly(methyl methacrylate) Demixed Surfaces.
Human platelets play a vital role in haemostasis, pathological bleeding and thrombosis. The haemostatic mechanism is concerned with the control of bleeding from injured blood vessels, whereby platelets interact with the damaged inner vessel wall to form a clot (thrombus) at the site of injury. This adhesion of platelets and their subsequent aggregation is dependent on the presence of the blood protein von Willebrand Factor (vWF). It is proposed here that the entrapment of vWF on a substrate surface offers the opportunity to assess an individual's platelet function in a clinical diagnostic context. Spin coating from demixed solutions of polystyrene (PS) and poly(methyl methacrylate) (PMMA) onto glass slides has been shown previously to support platelet adhesion but the mechanism by which this interaction occurs, including the role of vWF, is not fully understood. In this work, we report a study of the interaction of platelets in whole blood with surfaces produced by spin coating from a solution of a weight/weight mixture of a 25% PS and 75% PMMA (25PS/75PMMA) in chloroform in the context of the properties required for their use as a Dynamic Platelet Function Assay (DPFA) substrate. Atomic Force Microscopy (AFM) indicates the presence of topographical features on the polymer demixed surfaces in the sub-micron to nanometer range. X-ray Photoelectron Spectroscopy (XPS) analysis confirms that the uppermost surface chemistry of the coatings is solely that of PMMA. The deliberate addition of various amounts of 50 μm diameter PS microspheres to the 25PS/75PMMA system has been shown to maintain the PMMA chemistry, but to significantly change the surface topography and to subsequently effect the scale of the resultant platelet interactions. By blocking specific platelet binding sites, it has been shown that their interaction with these surfaces is a consequence of the entrapment and build-up of vWF from the same whole blood sample.


The Optical Society's 2016 topical meeting on optical interference coatings: introduction.
This feature issue of Applied Optics is dedicated to the 13th Topical Meeting on Optical Interference Coatings, which was held June 19-24, 2016, in Tucson, Arizona, USA. The conference, taking place every three years, is a focal point for global technical interchange in the field of optical interference coatings and provides premier opportunities for people working in the field to present their new advances in research and development. Papers presented at the meeting covered a broad range of topics, including fundamental research on coating design theory, new materials, and deposition and characterization technologies, as well as the vast and growing number of applications in electronic displays, communication, optical instruments, high power and ultra-fast lasers, solar cells, space missions, gravitational wave detection, and many others.


Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies.
Alpha-2-macroglobulin is an abundant secreted protein that is of particular interest because of its diverse ligand binding profile and multifunctional nature, which includes roles as a protease inhibitor and as a molecular chaperone. The activities of alpha-2-macroglobulin are typically dependent on whether its conformation is native or transformed (i.e. adopts a more compact conformation after interactions with proteases or small nucleophiles), and are also influenced by dissociation of the native alpha-2-macroglobulin tetramer into stable dimers. Alpha-2-macroglobulin is predominately present as the native tetramer in vivo; once purified from human blood plasma, however, alpha-2-macroglobulin can undergo a number of conformational changes during storage, including transformation, aggregation or dissociation. We demonstrate that, particularly in the presence of sodium chloride or amine containing compounds, freezing and/or lyophilization of alpha-2-macroglobulin induces conformational changes with functional consequences. These conformational changes in alpha-2-macroglobulin are not always detected by standard native polyacrylamide gel electrophoresis, but can be measured using bisANS fluorescence assays. Increased surface hydrophobicity of alpha-2-macroglobulin, as assessed by bisANS fluorescence measurements, is accompanied by (i) reduced trypsin binding activity, (ii) increased chaperone activity, and (iii) increased binding to the surfaces of SH-SY5Y neurons, in part, via lipoprotein receptors. We show that sucrose (but not glycine) effectively protects native alpha-2-macroglobulin from denaturation during freezing and/or lyophilization, thereby providing a reproducible method for the handling and long-term storage of this protein.


Neonatal severe bacterial infection impairment estimates in South Asia, sub-Saharan Africa, and Latin America for 2010.
Survivors of neonatal infections are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified and yet important for program priority setting. Systematic reviews and meta-analyses were undertaken and applied in a three-step compartmental model to estimate NDI cases after severe neonatal bacterial infection in South Asia, sub-Saharan Africa, and Latin America in neonates of >32 wk gestation (or >1,500 g). We estimated cases of sepsis, meningitis, pneumonia, or no severe bacterial infection from among estimated cases of possible severe bacterial infection ((pSBI) step 1). We applied respective case fatality risks ((CFRs) step 2) and the NDI risk among survivors (step 3). For neonatal tetanus, incidence estimates were based on the estimated deaths, CFRs, and risk of subsequent NDI. For 2010, we estimated 1.7 million (uncertainty range: 1.1-2.4 million) cases of neonatal sepsis, 200,000 (21,000-350,000) cases of meningitis, 510,000 cases (150,000-930,000) of pneumonia, and 79,000 cases (70,000-930,000) of tetanus in neonates >32 wk gestation (or >1,500 g). Among the survivors, we estimated moderate to severe NDI after neonatal meningitis in 23% (95% confidence interval: 19-26%) of survivors, 18,000 (2,700-35,000) cases, and after neonatal tetanus in 16% (6-27%), 4,700 cases (1,700-8,900). Data are lacking for impairment after neonatal sepsis and pneumonia, especially among those of >32 wk gestation. Improved recognition and treatment of pSBI will reduce neonatal mortality. Lack of follow-up data for survivors of severe bacterial infections, particularly sepsis, was striking. Given the high incidence of sepsis, even minor NDI would be of major public health importance. Prevention of neonatal infection, improved case management, and support for children with NDI are all important strategies, currently receiving limited policy attention.


Sex chromosome turnover contributes to genomic divergence between incipient stickleback species.
Sex chromosomes turn over rapidly in some taxonomic groups, where closely related species have different sex chromosomes. Although there are many examples of sex chromosome turnover, we know little about the functional roles of sex chromosome turnover in phenotypic diversification and genomic evolution. The sympatric pair of Japanese threespine stickleback (Gasterosteus aculeatus) provides an excellent system to address these questions: the Japan Sea species has a neo-sex chromosome system resulting from a fusion between an ancestral Y chromosome and an autosome, while the sympatric Pacific Ocean species has a simple XY sex chromosome system. Furthermore, previous quantitative trait locus (QTL) mapping demonstrated that the Japan Sea neo-X chromosome contributes to phenotypic divergence and reproductive isolation between these sympatric species. To investigate the genomic basis for the accumulation of genes important for speciation on the neo-X chromosome, we conducted whole genome sequencing of males and females of both the Japan Sea and the Pacific Ocean species. No substantial degeneration has yet occurred on the neo-Y chromosome, but the nucleotide sequence of the neo-X and the neo-Y has started to diverge, particularly at regions near the fusion. The neo-sex chromosomes also harbor an excess of genes with sex-biased expression. Furthermore, genes on the neo-X chromosome showed higher non-synonymous substitution rates than autosomal genes in the Japan Sea lineage. Genomic regions of higher sequence divergence between species, genes with divergent expression between species, and QTL for inter-species phenotypic differences were found not only at the regions near the fusion site, but also at other regions along the neo-X chromosome. Neo-sex chromosomes can therefore accumulate substitutions causing species differences even in the absence of substantial neo-Y degeneration.


Selenium nanoparticles incorporated into titania nanotubes inhibit bacterial growth and macrophage proliferation.
Since implants often fail due to infection and uncontrolled inflammatory responses, we designed an in vitro study to investigate the antibacterial and anti-inflammatory properties of titanium dioxide nanotubes (TNTs) incorporated with selenium nanoparticles (SeNPs). Selenium incorporation was achieved by the reaction of sodium selenite (Na2SeO3) with glutathione (GSH) under a vacuum in the presence of TNTs. Two types of bacteria and macrophages were cultured on the samples to determine their respective antibacterial and anti-inflammatory properties. The results showed that the TNT samples incorporating SeNPs (TNT-Se) inhibited the growth of Escherichia coli and Staphylococcus aureus compared to unmodified TNTs, albeit the SeNP concentration still needs to be optimized for maximal effect. At their maximum effect, the TNT-Se samples reduced the density of E. coli by 94.6% and of S. aureus by 89.6% compared to titanium controls. To investigate the underlying mechanism of this effect, the expression of six E. coli genes were tracked using qRT-PCR. Results indicated that SeNPs weakened E. coli membranes (ompA and ompF were down-regulated), decreased the function of adhesion-mediating proteins (csgA and csgG were progressively down-regulated with increasing SeNP content), and induced the production of damaging reactive oxygen species (ahpF was up-regulated). Moreover, TNT-Se samples inhibited the proliferation of macrophages, indicating that they can be used to control the inflammatory response and even prevent chronic inflammation, a condition that often leads to implant failure. In conclusion, we demonstrated that SeNP-TNTs display antibacterial and anti-inflammatory properties that are promising for improving the performance of titanium-based implants for numerous orthopedic and dental applications.


Coordinated expression of splice variants for luteinizing hormone receptor messenger RNA during the development of bovine corpora lutea.
We characterized splice variants for LH receptor mRNA in the bovine corpus luteum and examined the levels of expression of all the splice variants during the development of corpus luteum. Total RNA was extracted from bovine corpora lutea, and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify a part of the extracellular and transmembrane domains. As a result, four distinct bands were observed on analyses with polyacrylamide gel electrophoresis, and sequencing of the products revealed that the largest form (519 bp) was the full-length A form and that the three shorter forms (438, 253, and 172 bp) were its splicing variants. Splicing patterns of the 438-, 253-, and 172-bp forms are identical to the F, B, and G forms, respectively, found in the ovine ovary. In order to examine the level of expression of all these splice variants simultaneously, semiquantitative RT-PCR was set up and performed. The relative intensities for all four forms of LH receptor mRNA significantly increased (P < 0.05) from Stage I (Days 1-4; Day 1 = day of ovulation) to IIS (Days 5-10, CL weight < 4 g), and from Stage IIS to IIL (Days 5-10, CL weight > or = 4 g). The intensities of all forms for LH receptor mRNA decreased slightly, but not significantly, from Stage IIL to III (Days 11-17). The ratios of the levels for all the forms did not change significantly during the development of the corpus luteum. Determination of the steady-state levels of LH receptor mRNA by Northern blotting showed similar changes during the development of the corpus luteum to changes of the splice variants examined by the semiquantitative RT-PCR. These results suggest that at least three splicing variants of LH receptor mRNA (i.e., F, B, and G forms) exist in the bovine corpus luteum and that the levels of all the forms of LH receptor mRNA increased in a coordinated manner during the development of bovine corpus luteum.


Lactobacillus crispatus dominant vaginal microbiome is associated with inhibitory activity of female genital tract secretions against Escherichia coli.
Female genital tract secretions inhibit E. coli ex vivo and the activity may prevent colonization and provide a biomarker of a healthy microbiome. We hypothesized that high E. coli inhibitory activity would be associated with a Lactobacillus crispatus and/or jensenii dominant microbiome and differ from that of women with low inhibitory activity. Vaginal swab cell pellets from 20 samples previously obtained in a cross-sectional study of near-term pregnant and non-pregnant healthy women were selected based on having high (>90% inhibition) or low (<20% inhibition) anti-E. coli activity. The V6 region of the 16S ribosomal RNA gene was amplified and sequenced using the Illumina HiSeq 2000 platform. Filtered culture supernatants from Lactobacillus crispatus, Lactobacillus iners, and Gardnerella vaginalis were also assayed for E. coli inhibitory activity. Sixteen samples (10 with high and 6 with low activity) yielded evaluable microbiome data. There was no difference in the predominant microbiome species in pregnant compared to non-pregnant women (n = 8 each). However, there were significant differences between women with high compared to low E. coli inhibitory activity. High activity was associated with a predominance of L. crispatus (p<0.007) and culture supernatants from L. crispatus exhibited greater E. coli inhibitory activity compared to supernatants obtained from L. iners or G. vaginalis. Notably, the E. coli inhibitory activity varied among different strains of L. crispatus. Microbiome communities with abundant L. crispatus likely contribute to the E. coli inhibitory activity of vaginal secretions and efforts to promote this environment may prevent E. coli colonization and related sequelae including preterm birth.


Comparative study of the acute toxicity of anionic surfactans alkyl benzene sulphonate (ABS) and sodium dodecyl sulphate (SDS) on gilthead, Sparus aurata L., eggs.
In the present work we have evaluated the acute toxicity of two anionic surfactants, alkyl benzene sulphonate (ABS) and sodium dodecyl sulphate (SDS) to eggs of gilthead Sparus aurata. At each surfactant concentration, we determined the exposure time required for 50% mortality of the eggs (LT50), surface tension and volume of oil globule in gilthead eggs. Clear dose-response relationships for mortality of gilthead eggs was observed for both toxicants; at 30 mg/L 50% mortality took place at 45 minutes for ABS and 8 minutes for SDS. At this concentration, SDS was almost six times more toxic than ABS (LT50 is compared). However, at 0.3 mg/L 50% mortality occurred after exposures of 535 minutes to ABS and 425 minutes to SDS. Descriptively, our results showed SDS was more toxic than ABS at high concentrations whereas at low concentrations their toxicity was very similar. However, statistical analysis demonstrated there were no significant differences in the toxicity of both surfactants to gilthead eggs. Surface tension value at each concentration of both surfactants was also calculated. We found that these values decreased with increasing concentration of each surfactant, and this trend was more pronounced in solutions of SDS. We also found that the volume of the oil globule of exposed eggs was influenced by surfactants. After exposure, its volume clearly decreased in comparison to controls, mainly in eggs exposed to SDS.


Improving Waste Segregation in the Operating Room to Decrease Overhead Cost.
Operating rooms (ORs) disproportionally contribute 20% to 33% of hospital waste nationwide and therefore have a major impact on hospital waste management. Seventy percent of general OR waste is incorrectly eliminated as clinical waste, which compounds unnecessary financial burden and produces negative environmental impact. The primary purpose of this quality improvement (QI) project was to evaluate the effectiveness of waste segregation education for OR anesthesia staff on improving waste segregation compliance in the OR. A waste segregation QI project was implemented at a 19-OR hospital. Sharps bins in each OR were monitored for weight in pounds and 6 ORs were monitored for percent compliance both pre- and post-institution of a waste segregation education. In addition, a waste segregation knowledge assessment, waste segregation barriers assessment, and a demographic survey were administered to anesthesia staff. Twenty-two certified registered nurse anesthetists (CRNAs), 13 anesthesiologists, and 4 anesthesia technicians responded to the initial surveys and assessments while 30 of these original 39 participants (77%) responded following the educational intervention. A cost analysis was calculated pre- and post-implementation by multiplying total weight of the sharps bins by the price per pound of sharps. Twenty-three percent of participants reported having formal waste segregation training. Survey responses revealed that the greatest barrier to waste segregation involved bin location (56.4%), followed by lack of time to segregate (25.6%), lack of knowledge of what content goes in the bin (25.6%), and lack of incentive (25.6%). A waste segregation knowledge assessment showed improvement from pre- (M = 9.18, SD = 1.66) to post-implementation (M = 9.90, SD = 1.64). Pre-implementation sharps bin compliance was 50.70% while post-implementation bin compliance improved to 58.44%. A 27.64% decrease in sharps disposal cost occurred following implementation, which is estimated to produce a $2964 cost savings per year. Waste segregation education for anesthesia staff increased their waste management knowledge, improved sharps waste bin compliance, and produced an overall cost savings.


Assessing agreement with relative area under the coverage probability curve.
There has been substantial statistical literature in the last several decades on assessing agreement, and coverage probability approach was selected as a preferred index for assessing and improving measurement agreement in a core laboratory setting. With this approach, a satisfactory agreement is based on pre-specified high satisfactory coverage probability (e.g., 95%), given one pre-specified acceptable difference. In practice, we may want to have quality control on more than one pre-specified differences, or we may simply want to summarize the agreement based on differences up to a maximum acceptable difference. We propose to assess agreement via the coverage probability curve that provides a full spectrum of measurement error at various differences/disagreement. Relative area under the coverage probability curve is proposed for the summary of overall agreement, and this new summary index can be used for comparison of different intra-methods or inter-methods/labs/observers' agreement. Simulation studies and a blood pressure example are used for illustration of the methodology. Copyright © 2016 John Wiley & Sons, Ltd.


Societal shifts due to COVID-19 reveal large-scale complexities and feedbacks between atmospheric chemistry and climate change.
The COVID-19 global pandemic and associated government lockdowns dramatically altered human activity, providing a window into how changes in individual behavior, enacted en masse, impact atmospheric composition. The resulting reductions in anthropogenic activity represent an unprecedented event that yields a glimpse into a future where emissions to the atmosphere are reduced. Furthermore, the abrupt reduction in emissions during the lockdown periods led to clearly observable changes in atmospheric composition, which provide direct insight into feedbacks between the Earth system and human activity. While air pollutants and greenhouse gases share many common anthropogenic sources, there is a sharp difference in the response of their atmospheric concentrations to COVID-19 emissions changes, due in large part to their different lifetimes. Here, we discuss several key takeaways from modeling and observational studies. First, despite dramatic declines in mobility and associated vehicular emissions, the atmospheric growth rates of greenhouse gases were not slowed, in part due to decreased ocean uptake of CO2 and a likely increase in CH4 lifetime from reduced NO x emissions. Second, the response of O3 to decreased NO x emissions showed significant spatial and temporal variability, due to differing chemical regimes around the world. Finally, the overall response of atmospheric composition to emissions changes is heavily modulated by factors including carbon-cycle feedbacks to CH4 and CO2, background pollutant levels, the timing and location of emissions changes, and climate feedbacks on air quality, such as wildfires and the ozone climate penalty.


Prediction of Long-term Cognitive Functions after Minor Stroke, Using Functional Connectivity.
To determine whether functional MRI connectivity can predict the long-term cognitive functions 36 months after minor stroke. Seventy-two participants with first-ever stroke were included at baseline and followed up for 36 months. A ridge regression machine learning algorithm was developed and used to predict cognitive scores 36 months post-stroke on the basis of the functional networks measured using MRI at 6 months (referred to here as the post-stroke cognitive impairment (PSCI) network). The prediction accuracy was evaluated in four domains (memory, attention/executive, language and visuospatial functions) and compared with clinical data and other functional networks. The models' statistical significance was probed with permutation tests. The potential involvement of cortical atrophy was assessed 6 months post-stroke. A second, independent dataset (n=40) was used to validate the results and assess their generalizability. Based on the PSCI network, a machine learning model was able to predict memory, attention, visuospatial functions and language functions 36 months post-stroke (r2: 0.67, 0.73, 0.55 and 0.48, respectively). The PSCI-based model was at least as accurate as models based on other functional networks or clinical data. Specific patterns were demonstrated for the four cognitive domains, with involvement of the left superior frontal cortex for memory, attention and visuospatial functions. The cortical thickness 6 months post-stroke was not correlated with cognitive function 36 months post-stroke. The independent validation dataset gave similar results. A machine learning model based on the PSCI network can predict the long-term cognitive outcome after stroke.


Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases.
Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies. Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts. Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab). In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes.


Short-loop feedback control of luteinizing hormone in the rabbit.
A radioimmunoassay for rabbit luteinizing hormone (rLH) in which rLH shows no significant cross-reaction with human LH (hLH) or human chorionic gonadotropin (HCG) was employed to test for the existence of a short-loop feedback for LH in the rabbit. Two weeks after castration, hCG and hLH were administered intravenously to rabbits, and the effects on circulating rLH were measured. Purified hLH (10 ng or 100 IU) produced significant depression of blood rLH within 30-60 min of intravenous injection. Saline administered to the same animals produced no changes in rLH. Injection of hCG (2,000 IU) under the same conditions also produced a significant fall in rLH. However, hCG administered to rabbits castrated 6 wk prior to study failed to suppress endogenous rLH. These data demonstrate, by direct radioimmunoassay quantification of blood hormones, the existence of a short-loop negative feedback for LH in the rabbit. They also suggest that the sensitivity of the short-loop changes with time after castration.


Cid1, a fission yeast protein required for S-M checkpoint control when DNA polymerase delta or epsilon is inactivated.
The S-M checkpoint is an intracellular signaling pathway that ensures that mitosis is not initiated in cells undergoing DNA replication. We identified cid1, a novel fission yeast gene, through its ability when overexpressed to confer specific resistance to a combination of hydroxyurea, which inhibits DNA replication, and caffeine, which overrides the S-M checkpoint. Cid1 overexpression also partially suppressed the hydroxyurea sensitivity characteristic of DNA polymerase delta mutants and mutants defective in the "checkpoint Rad" pathway. Cid1 is a member of a family of putative nucleotidyltransferases including budding yeast Trf4 and Trf5, and mutation of amino acid residues predicted to be essential for this activity resulted in loss of Cid1 function in vivo. Two additional Cid1-like proteins play similar but nonredundant checkpoint-signaling roles in fission yeast. Cells lacking Cid1 were found to be viable but specifically sensitive to the combination of hydroxyurea and caffeine and to be S-M checkpoint defective in the absence of Cds1. Genetic data suggest that Cid1 acts in association with Crb2/Rhp9 and through the checkpoint-signaling kinase Chk1 to inhibit unscheduled mitosis specifically when DNA polymerase delta or epsilon is inhibited.


Effects of massage on pain and anxiety during labour: a randomized controlled trial in Taiwan.
To investigate the effects of massage on pain reaction and anxiety during labour. Labour pain is a challenging issue for nurses designing intervention protocols. Massage is an ancient technique that has been widely employed during labour, however, relatively little study has been undertaken examining the effects of massage on women in labour. A randomized controlled study was conducted between September 1999 and January 2000. Sixty primiparous women expected to have a normal childbirth at a regional hospital in southern Taiwan were randomly assigned to either the experimental (n=30) or the control (n=30) group. The experimental group received massage intervention whereas the control group did not. The nurse-rated present behavioural intensity (PBI) was used as a measure of labour pain. Anxiety was measured with the visual analogue scale for anxiety (VASA). The intensity of pain and anxiety between the two groups was compared in the latent phase (cervix dilated 3-4 cm), active phase (5-7 cm) and transitional phase (8-10 cm). In both groups, there was a relatively steady increase in pain intensity and anxiety level as labour progressed. A t-test demonstrated that the experimental group had significantly lower pain reactions in the latent, active and transitional phases. Anxiety levels were only significantly different between the two groups in the latent phase. Twenty-six of the 30 (87%) experimental group subjects reported that massage was helpful, providing pain relief and psychological support during labour. Findings suggest that massage is a cost-effective nursing intervention that can decrease pain and anxiety during labour, and partners' participation in massage can positively influence the quality of women's birth experiences.


DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer.
There are two major molecular pathways to sporadic colorectal cancer, the chromosomal instability (CIN) and the CpG island methylator phenotype (CIMP) pathways. This study recruited 166 patients undergoing colonoscopy. Biopsy samples were collected from the cecum, transverse colon, sigmoid colon and rectum. DNA methylation was quantified at 'type A' (ESR1, GATA5, HIC1, HPP1, SFRP1) and 'type C' markers (MGMT, MLH1, CDKN2A, MINT2, MINT31, IGF2, CACNA1G, NEUROG1, SOCS1, RUNX3), and LINE-1. 'Type A' genes are frequently methylated in normal and neoplastic tissues, proportional to tissue age. 'Type C' methylation is more specific for neoplasia. The last five 'type C' markers comprise a CIMP panel. The mean 'type A' and CIMP-panel methylation Z-scores were calculated. In all, 88 patients had adenomatous lesions, 32 had proximal serrated polyps (PSPs) and 50 were normal. Most 'type A' genes showed direct correlations between methylation and age (ESR1, rho=0.66, P<0.0001), with higher methylation distally (ESR1, P<0.0001). On multivariate analysis, 'type A' methylation was inversely associated with colorectal adenomas (odds ratio=0.23, P<0.001), the precursor to CIN cancers. CIMP-panel methylation was significantly associated with advanced PSPs (odds ratio=5.1, P=0.009), the precursor to CIMP cancers. DNA methylation in normal mucosa varied with age and region and was associated with pathway-specific pathology. In the future, the colorectal field could yield important information and potentially inform clinical practice.


The supply chain of human pancreatic β cell lines.
Patients with type 1 or type 2 diabetes have an insufficiency in their functional β cell mass. To advance diabetes treatment and to work toward a cure, a better understanding of how to protect the pancreatic β cells against autoimmune or metabolic assaults (e.g., obesity, gestation) will be required. Over the past decades, β cell protection has been extensively investigated in rodents both in vivo and in vitro using isolated islets or rodent β cell lines. Transferring these rodent data to humans has long been challenging, at least partly for technical reasons: primary human islet preparations were scarce and functional human β cell lines were lacking. In 2011, we described a robust protocol of targeted oncogenesis in human fetal pancreas and produced the first functional human β cell line, and in subsequent years additional lines with specific traits. These cell lines are currently used by more than 150 academic and industrial laboratories worldwide. In this Review, we first explain how we developed the human β cell lines and why we think we succeeded where others, despite major efforts, did not. Next, we discuss the use of such functional human β cell lines and share some perspectives on their use to advance diabetes research.


The quest for an AIDS vaccine: is the CD8+ T-cell approach feasible?
The rationale for developing anti-HIV vaccines that stimulate cytotoxic T-lymphocyte responses is given. We argue that such vaccines will work, provided that attention is paid to the development of memory T-cell responses that are strong and preferably activated. Furthermore, the vaccine should match the prevailing virus clade as closely as possible. Vaccines will have to stimulate a wide range of responses, but it is not clear how this can be achieved.


Coloured overlays and precision-tinted lenses: poor repeatability in a sample of adults and children diagnosed with visual stress
Visual stress consists of perceived distortions or discomfort while reading. It is claimed that these symptoms are alleviated by viewing through coloured lenses or overlays, with a specific colour required for each individual. This has been explained on the basis of altered visual cortex excitation as affected by the spectral content of the viewing light. If symptoms are indeed alleviated by a particular colour that has an impact on the individual's visual system, we would expect that selection of the most beneficial colour would be repeatable. The aim of this study was to determine whether this is the case. Twenty-one participants (mean age 26 years (range 8-55 years); 12 female, nine male) with visual stress and no other uncorrected ocular or visual anomaly were recruited. Each participant selected the colour most beneficial in alleviating their symptoms from a standard set of 10 coloured overlays, and underwent intuitive colorimetry in which the most beneficial of a wide range of chromatic illuminance settings was selected. Without prescribing an overlay at the first appointment, this process was repeated on a second occasion at a mean of 25 days later. About half of the participants (n = 10) chose the same (n = 7) or similar (with one common colour in both choices; n = 3) coloured overlay on the two occasions, while 11 participants chose a completely different overlay colour. Across all participants, the colorimetry setting shifted by, on average, 9.6 just noticeable differences, indicating that the colours were perceptually very different. These findings suggest that people with visual stress are unlikely to find exactly the same colour to be optimal on different occasions, and raise questions about the need for precise colour specification in tinted lenses for visual stress.


Entropy-driven stability of chiral single-walled carbon nanotubes.
Single-walled carbon nanotubes are hollow cylinders that can grow centimeters long via carbon incorporation at the interface with a catalyst. They display semiconducting or metallic characteristics, depending on their helicity, which is determined during their growth. To support the quest for a selective synthesis, we develop a thermodynamic model that relates the tube-catalyst interfacial energies, temperature, and the resulting tube chirality. We show that nanotubes can grow chiral because of the configurational entropy of their nanometer-sized edge, thus explaining experimentally observed temperature evolutions of chiral distributions. Taking the chemical nature of the catalyst into account through interfacial energies, we derive structural maps and phase diagrams that will guide a rational choice of a catalyst and growth parameters toward a better selectivity.


The effect of randomised exposure to different types of natural outdoor environments compared to exposure to an urban environment on people with indications of psychological distress in Catalonia.
Experimental studies have reported associations between short-term exposure to natural outdoor environments (NOE) and health benefits. However, they lack insight into mechanisms, often have low external and ecological validity, and have rarely focused on people with some psycho-physiological affection. The aim of this study was to use a randomized, case-crossover design to investigate: (i) the effects of unconstrained exposure to real natural and urban environments on psycho-physiological indicators of people with indications of psychological distress, (ii) the possible differential effects of 30 and 30+180 minutes exposures, and (iii) the possible mechanisms explaining these effects. People (n = 26) with indications of psychological distress were exposed to green (Collserola Natural Park), blue (Castelldefels beach) and urban (Eixample neighbourhood) environments in Catalonia. They were exposed to all environments in groups for a period of 30+180 minutes between October 2013 and January 2014. During the exposure period, participants were instructed to do what they would usually do in that environment. Before, during (at 30 and 30+180 minutes) and after each exposure, several psycho-physiological measures were taken: mood (measured as Total Mood Disturbance, TMD), attention capacity (measured as backwards digit-span task), stress levels (measures as salivary cortisol), systolic and diastolic blood pressure, heart rate, autonomous nervous system (assessed as heart rate variability and the indicators: low frequency power (LF), high frequency power (HF), ratio between LF and HF (LF:HF), and coefficients of component variance of LF, HF, and LF:HF). We also measured several potential mediators: air pollution, noise, physical activity, social interactions, and self-perceived restoration experience. When compared with responses to urban environment, we found statistically significantly lower TMD [-4.78 (-7.77, -1.79) points difference], and salivary cortisol [-0.21 (-0.34, -0.08) log nmol/L] in the green exposure environment, and statistically significantly lower TMD [-4.53 (-7.57, -1.49) points difference], and statistically significant favourable changes in heart rate variability indicators (specifically LF:HF and CCV-LF:HF with around -0.20 points of difference of the indicators) in the blue exposure environment. Physical activity and self-perceived restoration experience partially mediated the associations between NOE and TMD. Physical activity and air pollution partially mediated the associations between NOE and heart rate variability. This study extends the existing evidence on the benefits of NOE for people's health. It also suggests NOE potential as a preventive medicine, specifically focusing on people with indications of psychological distress. Clinicaltrials.gov NCT02624921.


Micromechanical analyses of vertebral trabecular bone based on individual trabeculae segmentation of plates and rods.
Trabecular plates play an important role in determining elastic moduli of trabecular bone. However, the relative contribution of trabecular plates and rods to strength behavior is still not clear. In this study, individual trabeculae segmentation (ITS) and nonlinear finite element (FE) analyses were used to evaluate the roles of trabecular types and orientations in the failure initiation and progression in human vertebral trabecular bone. Fifteen human vertebral trabecular bone samples were imaged using micro computed tomography (microCT), and segmented using ITS into individual plates and rods by orientation (longitudinal, oblique, and transverse). Nonlinear FE analysis was conducted to perform a compression simulation for each sample up to 1% apparent strain. The apparent and relative trabecular number and tissue fraction of failed trabecular plates and rods were recorded during loading and data were stratified by trabecular orientation. More trabecular rods (both in number and tissue fraction) failed at the initiation of compression (0.1-0.2% apparent strain) while more plates failed around the apparent yield point (>0.7% apparent strain). A significant correlation between plate bone volume fraction (pBV/TV) and apparent yield strength was found (r(2)=0.85). From 0.3% to 1% apparent strain, significantly more longitudinal trabecular plate and transverse rod failed than other types of trabeculae. While failure initiates at rods and rods fail disproportionally to their number, plates contribute significantly to the apparent yield strength because of their larger number and tissue volume. The relative failed number and tissue fraction at apparent yield point indicate homogeneous local failure in plates and rods of different orientations.


Efficacy of disinfectants containing accelerated hydrogen peroxide against conidial arthrospores and isolated infective spores of Microsporum canis and Trichophyton sp.
Accelerated hydrogen peroxide is a proprietary disinfectant formulation that is available for both commercial and home use and is labelled as antifungal. To determine the antifungal efficacy of accelerated hydrogen peroxide disinfectants against Microsporum and Trichophyton spp. Three products formulated as ready to use and three concentrates were used. Concentrates were tested at dilutions of 1:8, 1:16 (recommended dilution) and 1:32. One product was a surgical instrument disinfectant. Sterile water, sodium hypochlorite (1:32 dilution) and over-the-counter 3% hydrogen peroxide were used as controls. Conidial suspensions contained ~9.6 × 10(5) /mL Microsporum canis, ~1.0 × 10(7) /mL M. gypseum or ~2.0 × 10(7) /mL Trichophyton sp. and were tested at 1:10 dilution. Isolated infective spore suspensions of M. canis from an untreated cat and T. erinacei from an untreated hedgehog were tested at 1:10, 1:5 and 1:1 spore-to-disinfectant dilutions. Too many colonies to count were present on untreated control plates. Accelerated hydrogen peroxide and household hydrogen peroxide inhibited growth of both pathogens in conidial (1:10 dilution) and spore suspensions (1:10, 1:5 and 1:10 dilution). There was no lack of efficacy of products that were >12 months old. Accelerated hydrogen peroxide products are an option for environmental disinfection of surfaces exposed to M. canis and Trichophyton sp. after appropriate gross decontamination and mechanical cleaning with a detergent. The results from conidial testing were identical to those of isolated infected spore testing, which suggests that accelerated hydrogen peroxide products with label claim as antifungal against Trichophyton mentagrophytes may be suitable as an alternative disinfectant to sodium hypochlorite.


Agrimonia eupatoria L. and Cynara cardunculus L. Water Infusions: Comparison of Anti-Diabetic Activities.
Diabetes mellitus (DM) is frequently diagnosed at a time when patients already suffer from several cardiovascular complications. Our previously published data (Molecules 201520 (11): 20538-50) on the anti-oxidative properties of Agrimonia eupatoria L. (AE) and Cynara cardunculus L. (CC) prompted us to extend the available evidence on their possible protective activities on selected DM-related parameters in a streptozotocin-induced DM rat model and in a series of in vitro experiments. Male rats were divided into four groups: control group, untreated diabetic group, AE and CC treated diabetic groups. During a five-week period, changes in blood glucose and body weight were monitored. Then, rats were sacrificed and subjected to the assessment of changes in the reactivity of aortas and measurement of butyrylcholinesterase activity. To complete the panel of experiments, α-glucosidase activity was assessed in vitro. Our results demonstrate that both tested extracts exert similar anti-diabetic activities. However, better anti-oxidant activity of the A. eupatoria extract indicates its higher clinical potential in the prevention and/or adjuvant therapy of developing cardiovascular complications related to DM and diseases associated with oxidative stress.