Building Indigenous health workforce capacity and capability through leadership - the Miwatj health leadership model.
In the crowded field of leadership research, Indigenous leadership remains under-researched. This article explores the Leadership Model of an Aboriginal Community Controlled Primary Health Care Organisation providing services to the Yolngu people of remote northern Australia: the Miwatj Health Aboriginal Corporation (Miwatj). The limited research which does exist on Indigenous leadership points to unique challenges for Indigenous leaders. These challenges relate to fostering self-determination in their communities, managing significant community expectations, and navigating a path between culturally divergent approaches to management and leadership. Guided by Indigenous methodology and using a mixed methods approach, semi-structured interviews, self-reported health service data, organisational and publicly available documents, and literature were analysed using a framework method of thematic analysis to identify key themes of the Miwatj Leadership Model. The Miwatj Leadership Model is underpinned by three distinctive elements: it offers Yolngu people employment opportunities; it supports staff who want to move into leadership positions and provides capacity building through certificates and diplomas; and it provides for the physical, emotional, and cultural wellbeing of all Yolngu staff. Furthermore, the model respects traditional Yolngu forms of authority and empowers the community to develop, manage and sustain their own health. The Miwatj Leadership Model has been successful in providing formal pathways to support Indigenous staff to take on leadership roles, and has improved the accessibility and acceptability of health care services as a result of Yolngu employment and improved cultural safety. Translating the Miwatj Leadership Model into other health services will require considerable thought and commitment. The Miwatj Leadership Model can be adapted to meet the needs of other health care services in consideration of the unique context within which they operate. This study has demonstrated the importance of having a formal leadership model that promotes recruitment, retention, and career progression for Indigenous staff.


Cognitive control exertion leads to reductions in peak power output and [Formula: see text] as well as increased perceived exertion on a graded exercise test to exhaustion.
We investigated effects of a brief (10.5 min) cognitively demanding task on graded exercise test performance. Untrained, university students (N = 15) completed two graded exercise tests in counterbalanced, randomised order. One test was preceded by restful viewing of a documentary video (control); the other by a stop-signal task. Cardiorespiratory functions and perceived exertion were monitored during exercise. Peak power output (W) was lower following the stop-signal task (M = 240.03, SD = 53.37) compared to control (M = 246.03, SD = 52.60), P = 0.002, ηP2 = 0.493, as was [Formula: see text] (P = 0.042, Cohen's d = 0.55). Perceived exertion was significantly higher at 50% (d = 0.77) and 75% (d = 0.83) of iso-time following the cognitive task (Ps ≤ 0.01). Results are consistent with research showing negative carryover effects of cognitively demanding tasks on whole-body endurance performance. Results also support the psychobiological model of exercise as performance of the cognitive task did not affect perceived exertion when exercise task demands were lower, but lead to greater perceived exertion and earlier withdrawal of effort at higher levels of exercise task demand. Findings have implications for understanding psychological determinants of exercise performance and conditions that may lead to underestimation of [Formula: see text].


Second prostaglandin F2α treatment during Ovsynch protocol does not improve fertility outcomes in dairy cows.
The objective of this study was to evaluate the effect of a second prostaglandin F2α (PGF2α) treatment during Ovsynch on luteal regression and fertility in dairy cows, compared with standard Ovsynch. The study was conducted on 111 Holstein Friesian multiparous cows on commercial dairy farm. The cows in the experimental group (n=48) received two treatments of PGF2α 24 hours apart during Ovsynch. The cows in the control group (n=63) were synchronized with standard Ovsynch. To assess the progesterone (P4) concentration blood samples were collected at the day of PGF2α treatment and at the 2nd GnRH treatment. Pregnancy was evaluated by ultrasound examination 37-40 days after timed artificial insemination (TAI) by ultrasound. Cows diagnosed pregnant were re-examined between days 70-80 after TAI. The percentage of cows with complete corpus luteum (CL) regression (P4⟨0.5 ng/ml at the time of the 2nd GnRH treatment) was 89.6 % after two PGF2α treatments and 88.9 % after one PGF2α treatment. There were no statistically significant differences (p>0.05) in the pregnancies per artificial insemination (P/AI) between the experimental and control group (P/AI). However, the pregnancy loss rate was lower in cows receiving two PGF2α treatments than in the control animals (0.0 % vs. 6.4 %; p⟨0.05). In conclusion, the second PGF2α treatment during Ovsynch protocol had no significant effect on CL regression and P/AI in dairy cows. The pregnancy losses until days 75-80 after TAI were significantly lower after two PGF2α treatments than after one PGF2α treatment.


Ion selectivity of graphene nanopores.
As population growth continues to outpace development of water infrastructure in many countries, desalination (the removal of salts from seawater) at high energy efficiency will likely become a vital source of fresh water. Due to its atomic thinness combined with its mechanical strength, porous graphene may be particularly well-suited for electrodialysis desalination, in which ions are removed under an electric field via ion-selective pores. Here, we show that single graphene nanopores preferentially permit the passage of K(+) cations over Cl(-) anions with selectivity ratios of over 100 and conduct monovalent cations up to 5 times more rapidly than divalent cations. Surprisingly, the observed K(+)/Cl(-) selectivity persists in pores even as large as about 20 nm in diameter, suggesting that high throughput, highly selective graphene electrodialysis membranes can be fabricated without the need for subnanometer control over pore size.


Immunohistochemical distinction of primary adrenal cortical lesions from metastatic clear cell renal cell carcinoma: a study of 248 cases.
The diagnosis of metastatic clear cell renal cell carcinoma (CC-RCC) can be difficult because of its morphologic heterogeneity and the increasing use of small image-guided biopsies that yield scant diagnostic material. This is further complicated by the degree of morphologic and immunophenotypic overlap with nonrenal neoplasms and tissues, such as adrenal cortex. In this study, a detailed immunoprofile of 63 adrenal cortical lesions, which included 54 cortical neoplasms, was compared with 185 metastatic CC-RCCs using traditional [anticalretinin, CD10, antichromogranin, antiepithelial membrane antigen, anti-inhibin, antimelanA, anticytokeratins (AE1/AE3 and AE1/CAM5.2), antirenal cell carcinoma marker, and antisynaptophysin)] and novel [anticarbonic anhydrase-IX, antihepatocyte nuclear factor-1b, antihuman kidney injury molecule-1 (hKIM-1), anti-PAX-2, anti-PAX-8, antisteroidogenic factor-1 (SF-1), and anti-T-cell immunoglobulin mucin-1] antibodies. Tissue microarray methodology was used to simulate small image-guided biopsies. Staining extent and intensity were scored semiquantitatively for each antibody. In comparing different intensity thresholds required for a "positive" result, a value of ≥2+ was identified as optimal for diagnostic sensitivity/specificity. For the distinction of adrenal cortical lesions from metastatic CC-RCCs, immunoreactivity for the adrenal cortical antigens SF-1 (86% adrenal; 0% CC-RCC), calretinin (89% adrenal; 10% CC-RCC), inhibin (86% adrenal; 9% CC-RCC), and melanA (86% adrenal; 10% CC-RCC) and for the renal epithelial antigens hKIM-1 (0% adrenal; 83% CC-RCC), PAX-8 (0% adrenal; 83% CC-RCC), hepatocyte nuclear factor-1b (0% adrenal; 76% CC-RCC), epithelial membrane antigen (0% adrenal; 78% CC-RCC), and carbonic anhydrase-IX (3% adrenal; 87% CC-RCC) had the most potential use. Use of novel renal epithelial markers hKIM-1 (clone AKG7) and/or PAX-8 and the adrenocortical marker SF-1 in an immunohistochemical panel for distinguishing adrenal cortical lesions from metastatic CC-RCC offers improved diagnostic sensitivity and specificity.


Inhibitory effect of triptolide on interleukin-18 and its receptor in rheumatoid arthritis synovial fibroblasts.
To determine the effects of triptolide (TP) on the expression of interleukin-18 (IL-18) and its receptor in phorbol 12-myristate 13-acetate (PMA)-stimulated rheumatoid arthritis synovial fibroblasts (RASF). RASF were obtained from the synovial tissue of patients with RA. RASF were pretreated with TP (0~100 ng/ml) for 2 h before stimulation with PMA (50 ng/ml). The bioactivity of IL-18 in the supernatant was detected based on IFN-gamma secretion from IL-18-responding human myelomonocytic KG-1 cells. IL-18 level was analyzed by ELISA. In situ expression of IL-18Ralpha was determined by immunofluorescence assay. To estimate the protein and mRNA expression of IL-18 and IL-18Ralpha in RASF, western blot and quantitative RT-PCR were performed. Nuclear factor-kappaB (NF-kappaB) activity in the whole-cell extract of treated RASF was also measured using an ELISA-based method. TP effectively inhibited the bioactivity of IL-18 in PMA-stimulated RASF. The expression of IL-18 and IL-18R at protein and gene levels was reduced by TP. NF-kappaB activity in PMA-stimulated RASF was profoundly suppressed by TP. These effects showed a high correlation with TP concentration (0~100 ng/ml). TP effectively inhibited the expression of IL-18 and its receptor in PMA-stimulated RASF. These results suggest a mechanism of TP in RA therapy.


Psychosocial or clinico-demographic factors related to neuropsychiatric symptoms in patients with Alzheimer's disease needing interventional treatment: analysis of the CATIE-AD study.
This study sought to determine psychosocial and clinico-demographic factors related to each symptomatic cluster (i.e., aggressiveness, psychosis, apathy/eating problems, and emotion/disinhibition) of neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD) needing interventional treatment against their agitation or psychotic symptoms. These clusters were classified from 12 Neuropsychiatric Inventory (NPI) subscores in our previous study using the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) dataset. Based on clinical data from 421 AD outpatients with agitation or psychotic symptoms needed interventional treatment enrolled in the CATIE-AD, we conducted logistic regression analyses to examine the relationships between each symptomatic cluster and three psychosocial (marital status, residence, and caregivers' burden) and nine clinico-demographic (age, gender, education year, general cognition, activity of daily living [ADL], general medical health, race, and intake of anti-dementia drugs or psychotropics) factors. While no factor contributed to aggressiveness, psychosis was associated with several clinico-demographic factors: female gender, non-Caucasian race, and lower cognitive function. Apathy/eating problems was associated with more severe caregiver burden, living in one's own home, lower ADL level, and male gender, while emotion/disinhibition was predicted by more severe caregiver burden, lower education level, not-married status, and younger age. Among the four NPS clusters, apathy/eating problems and emotion/disinhibition were associated with psychosocial as well as clinico-demographic factors in AD patients with psychotic symptoms or agitation needed interventional treatment. Copyright © 2016 John Wiley & Sons, Ltd.


Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study.
Obesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased among infants who had overweight or obesity at birth, but in low-resource settings one in five infants are born small for gestational age. We aimed to study the relationships between: (1) maternal metabolite signatures; (2) fetal abdominal growth; and (3) postnatal growth, adiposity, and neurodevelopment. In the prospective, multinational, observational INTERBIO-21st fetal study, conducted in maternity units in Pelotas (Brazil), Nairobi (Kenya), Karachi (Pakistan), Soweto (South Africa), Mae Sot (Thailand), and Oxford (UK), we enrolled women (≥18 years, with a BMI of less than 35 kg/m2, natural conception, and a singleton pregnancy) who initiated antenatal care before 14 weeks' gestation. Ultrasound scans were performed every 5±1 weeks until delivery to measure fetal growth and feto-placental blood flow, and we used finite mixture models to derive growth trajectories of abdominal circumference. The infants' health, growth, and development were monitored from birth to age 2 years. Early pregnancy maternal blood and umbilical cord venous blood samples were collected for untargeted metabolomic analysis. From Feb 8, 2012, to Nov 30, 2019, we enrolled 3598 pregnant women and followed up their infants to 2 years of age. We identified four ultrasound-derived trajectories of fetal abdominal circumference growth that accelerated or decelerated within a crucial 20-25 week gestational age window: faltering growth, early accelerating growth, late accelerating growth, and median growth tracking. These distinct phenotypes had matching feto-placental blood flow patterns throughout pregnancy, and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood. There were 709 maternal metabolites with positive effect for the faltering growth phenotype and 54 for the early accelerating growth phenotype; 31 maternal metabolites had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype. Metabolites associated with the faltering growth phenotype had statistically significant odds ratios close to 1·5 (ie, suggesting upregulation of metabolic pathways of impaired fetal growth). The metabolites had a reciprocal relationship with the early accelerating growth phenotype, with statistically significant odds ratios close to 0.6 (ie, suggesting downregulation of fetal growth acceleration). The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid, and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was highly abundant in the early accelerating growth phenotype group. Early pregnancy lipid biology associated with fetal abdominal growth trajectories is an indicator of patterns of growth, adiposity, vision, and neurodevelopment up to the age of 2 years. Our findings could contribute to the earlier identification of infants at risk of obesity. Bill & Melinda Gates Foundation.


Fully Automated Habenula Segmentation Provides Robust and Reliable Volume Estimation Across Large Magnetic Resonance Imaging Datasets, Suggesting Intriguing Developmental Trajectories in Psychiatric Disease.
Studies of habenula (Hb) function and structure provided evidence of its involvement in psychiatric disorders, including schizophrenia and bipolar disorder. Previous studies using magnetic resonance imaging (manual/semiautomated segmentation) have reported conflicting results. Aiming to improve Hb segmentation reliability and the study of large datasets, we describe a fully automated protocol that was validated against manual segmentations and applied to 3 datasets (childhood/adolescence and adult bipolar disorder and schizophrenia). It achieved reliable Hb segmentation, providing robust volume estimations across a large age range and varying image acquisition parameters. Applying it to clinically relevant datasets, we found smaller Hb volumes in the adult bipolar disorder dataset and larger volumes in the adult schizophrenia dataset compared with healthy control subjects. There are indications that Hb volume in both groups shows deviating developmental trajectories early in life. This technique sets a precedent for future studies, as it allows for fast and reliable Hb segmentation and will be publicly available.


Rhizobial synthesized cytokinins contribute to but are not essential for the symbiotic interaction between photosynthetic Bradyrhizobia and Aeschynomene legumes.
Cytokinins (CK) play an important role in the formation of nitrogen-fixing root nodules. It has been known for years that rhizobia secrete CK in the extracellular medium but whether they play a role in nodule formation is not known. We have examined this question using the photosynthetic Bradyrhizobium sp. strain ORS285 which is able to nodulate Aeschynomene afraspera and A. indica using a Nod-dependent or Nod-independent symbiotic process, respectively. CK profiling showed that the most abundant CK secreted by Bradyrhizobium sp. strain ORS285 are the 2MeS (2-methylthiol) derivatives of trans-zeatin and isopentenyladenine. In their pure form, these CK can activate legume CK receptors in vitro, and their exogenous addition induced nodule-like structures on host plants. Deletion of the miaA gene showed that transfer RNA degradation is the source of CK production in Bradyrhizobium sp. strain ORS285. In nodulation studies performed with A. indica and A. afraspera, the miaA mutant had a 1-day delay in nodulation and nitrogen fixation. Moreover, A. indica plants formed considerably smaller but more abundant nodules when inoculated with the miaA mutant. These data show that CK produced by Bradyrhizobium sp. strain ORS285 are not the key signal triggering nodule formation during the Nod-independent symbiosis but they contribute positively to nodule development in Aeschynomene plants.


Pathogenicity of Diatrypaceous Fungi on Grapevines in Australia.
In addition to Eutypa lata, which causes Eutypa dieback, numerous other fungi in the Diatrypaceae family have been isolated from diseased grapevines (Vitis vinifera) and other woody hosts. Pathogenicity trials comprising 70 strains of diatrypaceous fungi representing nine species in six genera were conducted to determine whether these fungi, collected in Australia, were pathogenic to grapevines. When inoculated into wounded trunks of 'Cabernet Sauvignon', eight species, including E. lata, E. leptoplaca, Cryptovalsa ampelina, C. rabenhorstii, Eutypella citricola, E. microtheca, Diatrypella vulgaris, and a Diatrype sp. produced necrotic lesions significantly longer than on controls. In addition, all nine species (including a Cryptosphaeria sp.) were reisolated from the margins of developing lesions and at varying distances above and below the point of inoculation. Diatrypaceous fungi were frequently isolated from asymptomatic or otherwise healthy tissue several centimeters ahead of the disease margin. Methods to control diseases associated with diatrypaceous fungi must take into account their propensity to colonize woody tissues ahead of or in the absence of visible symptoms. Current recommendations for the management of Eutypa dieback using remedial surgery and pruning wound protection appear sufficient for the control of the other diatrypaceous fungi included in this study.


Parenting style and adolescent fruit consumption.
The importance of the social environment for dietary behaviour has been highlighted in the past decade. A type of environmental influence that has received increasing research attention in recent years is the influence that parents can have on their children's dietary behaviour through food-related parenting practices. Much of the work done so far, however, has reported inconsistent findings and poorly understood mechanisms of influence. The present study aimed to explore the possible environmental influence of general parenting style on adolescent food choice patterns. Data were collected at schools (N=643; mean age 16.5 years), using self-administered questionnaires on parenting style, fruit intake behaviour and fruit-specific cognitions. Consistent and theoretically predictable differences were found between adolescents who described their parents as authoritative, authoritarian, indulgent or neglectful. Fruit consumption and fruit-specific cognitions were most favourable among adolescents who were being raised with an authoritative parenting style. Children of parents with indulgent parenting styles consumed more fruit than adolescents from authoritarian or neglectful homes. Consequences of these results for the interpretation of earlier studies on the influence of parenting practices are discussed, and a research model is proposed for future studies of parental influences on adolescent dietary behaviours.


The out-of-body experience: disturbed self-processing at the temporo-parietal junction.
Folk psychology postulates a spatial unity of self and body, a "real me" that resides in one's body and is the subject of experience. The spatial unity of self and body has been challenged by various philosophical considerations but also by several phenomena, perhaps most notoriously the "out-of-body experience" (OBE) during which one's visuo-spatial perspective and one's self are experienced to have departed from their habitual position within one's body. Here the authors marshal evidence from neurology, cognitive neuroscience, and neuroimaging that suggests that OBEs are related to a failure to integrate multisensory information from one's own body at the temporo-parietal junction (TPJ). It is argued that this multisensory disintegration at the TPJ leads to the disruption of several phenomenological and cognitive aspects of self-processing, causing illusory reduplication, illusory self-location, illusory perspective, and illusory agency that are experienced as an OBE.


Angiotensin II mesenteric and renal vasoregulation: dissimilar modulatory effects with nitroprusside.
The role of systemic arterial pressure for the vascular effects of angiotensin II (Ang II) and the interactions between Ang II and perfusion pressure-dependent local vascular control mechanisms are not well understood. This study addresses these aspects of exogenous Ang II in the mesenteric and renal regional circulations. Ang II was infused in incremental doses (0-200 microg/h) in anesthetized instrumented pigs (n=10). Renal and portal blood flows were measured by perivascular ultrasound. In the second part of the study, sodium nitroprusside (SNP) was infused at doses titrated to keep mean arterial pressure constant, in spite of concurrent Ang II administration. Powerful dose-dependent vasoconstrictions by Ang II were found in renal and mesenteric vascular beds (at highest Ang II doses vascular resistances increased by 109% and 88% respectively). Ang II-induced vasoconstriction was fully inhibited in the mesenteric, but not in the renal circulation, during conditions of constant mean arterial pressures achieved by SNP infusion. Mesenteric, but not renal, vasoconstriction by Ang II was inhibited by pharmacological maintenance of perfusion pressure. This could reflect differences between these vascular beds as regards the importance of co-acting myogenic pressure-dependent vasoconstriction. Alternatively, as the drug chosen for pressure control, sodium nitroprusside, serves as a nitric oxide donor, the relative balance between nitric oxide-mediated vasodilation and Ang II-induced vasoconstriction could have regional differences.


Washing of marine coastal sand in a batch reactor: sorption and desorption of BTEX.
This study addresses the issues related to decontamination of marine beach sand accidentally contaminated by petroleum products. Sorption and desorption of BTEX (i.e., benzene, toluene, ethylbenzene, and xylene) onto the sand from Uran Beach, located near the city of Mumbai, India, were studied, and isotherms were determined using the bottle point method to estimate sorption coefficients. Alternatively, QSARs (i.e., quantitative structure activity relationships) were developed and used to estimate the sorption coefficients. Experiments for kinetics of volatilization as well as for kinetics of sorption and desorption in the presence of volatilization were conducted in a fabricated laboratory batch reactor. A mathematical model describing the fate of volatile hydrophobic organic pollutants like BTEX (via sorption and desorption in presence of volatilization) in a batch sediment-washing reactor was proposed. The experimental kinetic data were compared with the values predicted using the proposed models for sorption and desorption, and the optimum values of overall mass transfer coefficients for sorption (K(s)a(s)) and desorption (K(d)a(d)) were estimated. This was achieved by minimization of errors while using the sorption coefficients (Kp) obtained from either laboratory isotherm studies or the QSARs developed in the present study. Independent experimental data were also collected and used for calibration of the model for volatilization, and the values of the overall mass transfer coefficient for volatilization (K(g)a(g)) were estimated for BTEX. In these exercises of minimization of errors, comparable cumulative errors were obtained from the use of Kp values derived from experimental isotherms and QSARs.


Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients.
This is the first study to identify lipidomic markers in plasma associated with response of acutely ill schizophrenia patients in response to specific antipsychotic treatments. The study population included 54 schizophrenia patients treated with antipsychotics for 6 weeks. Treatment led to significant improvement in positive and negative symptoms for 34 patients with little or no improvement for 20 patients. In addition, 37 patients showed an increase in body mass index after the 6 week treatment period, consistent with effects on metabolism and the association of such effects with symptom improvement. Profiling of plasma samples taken prior to therapy using liquid chromatography tandem mass spectrometry (LC-MS/MS) resulted in identification of 38, 10, and 52 compounds associated with the olanzapine, risperidone, and quetiapine treatment groups, which could be used to distinguish responders from non-responders. Limitations include the retroactive active nature of the study and the small sample size. Further investigations with larger sample sets could lead to the development of a molecular test that could be used to help psychiatrists determine the best treatment options for each patient.


Leveraging Combat Casualty Reporting in the Afghan National Army Special Operations Command for Evidence-Based Changes in the ANASOC School of Excellence.
The Afghan National Army Special Operations Command (ANASOC) uses several documents for casualty reporting. By analyzing these documents from a period of March to December 2018, the authors demonstrate the predominance of gunshot fatalities within ANASOC at approximately 63% of combat deaths and a high rate of prehospital death at approximately 97% of combat deaths. The data also demonstrate relatively few cases of long-term disability from ANASOC soldiers wounded in action. The authors used these conclusions to create a Combined Joint Special Operations Task Force-Afghanistan (CJSOTF-A) working group that recommended changes to the medical curriculum at the ANASOC School of Excellence. These recommendations centered on an increased emphasis on bleeding control to prevent death from hemorrhagic shock.


Computerized literature searching in a teaching family practice center.
Computerized literature searching was introduced into a family practice residency office site after a series of training sessions. BRS Colleague was the searching program used. Over 15 months, 147 searches were conducted, primarily by faculty. Because residents used the system infrequently, they preferred to find a faculty member to help with the search rather than complete the search by themselves. The mean number of searches per faculty user was 6.4 and the median number of documents found per search was 15. The users were moderately satisfied with the search process (2.4 on a scale of 1 as excellent to 5 as unusable). Search strategies tended to be unsophisticated, often using only one of several possible related search terms. Most searches took a limited amount of time (5 to 20 minutes). The program was sufficiently successful to warrant continuation. Computerized literature searching offers a method to meet the physicians' needs for ready access to information on patient-related questions.


Efficacy and safety of mizoribine for the treatment of Sjögren's syndrome: a multicenter open-label clinical trial.
This multicenter clinical trial was performed to evaluate the efficacy and safety of mizoribine for the treatment of Sjögren's syndrome. Fifty-nine patients with a definite diagnosis of Sjögren's syndrome received 150;Smg of mizoribine daily for 16 weeks. The salivary secretion volume was determined at baseline, at weeks 8 and 16 after the start of the study treatment by the Saxon test, and clinical manifestations were assessed by the investigator and the patients using a 10-cm visual analog scale (VAS). Adverse drug reactions were reported in 18 patients, of whom 6 patients had to discontinue the study due to such adverse reactions; however, no serious adverse drug reactions definitely related to the study drug were noted. The salivary secretion volume, the rate of change in salivary secretion, the patients' own assessments of dry mouth and dry eyes, the investigators' assessment of oral sicca symptoms, and the investigators' overall assessment improved following the treatment regimen with statistical significance at week 16 after the start of treatment in comparison to the baseline values. These results suggested that mizoribine may be effective in producing a subjective and objective amelioration of the glandular symptoms in patients with Sjögren's syndrome, without observing any serious adverse effects related to this drug.


Phytophthora species in forest streams in Oregon and Alaska.
Eighteen Phytophthora species and one species of Halophytophthora were identified in 113 forest streams in Alaska, western Oregon and southwestern Oregon that were sampled by baiting or filtration of stream water with isolation on selective media. Species were identified by morphology and DNA characterization with single strand conformational polymorphism, COX spacer sequence and ITS sequence. ITS Clade 6 species were most abundant overall, but only four species, P. gonapodyides (37% of all isolates), P. taxon Salixsoil, P. taxon Oaksoil and P. pseudosyringae, were found in all three regions. The species assemblages were similar in the two Oregon regions, but P. taxon Pgchlamydo was absent in Alaska and one new species present in Alaska was absent in Oregon streams. The number of Phytophthora propagules in Oregon streams varied by season and in SW Oregon, where sampling continued year round, P. taxon Salixsoil, P. nemorosa and P. siskiyouensis were recovered only in some seasons.


Fatal falciparum malaria in Canadian travellers.
The authors report 2 cases of severe falciparum malaria in Canadians that had fatal outcomes. In the first case a man presented to a local hospital shortly after returning from Africa, but a diagnosis of malaria was not considered. He was transferred to a secondary and then to a tertiary care facility, where he subsequently died. Intravenous quinidine therapy, the treatment of choice, was unavailable at all 3 hospitals. In the second case, a woman taking chloroquine prophylaxis while visiting Nigeria developed cerebral malaria and died. These cases illustrate critical management issues: appropriate advice on malaria prevention before departure; consideration of malaria in all febrile people returning from an endemic area; ready access to parenteral therapy for severe malaria in Canadian hospitals; and an increase in awareness of travel medicine among family physicians.


Mainstreaming biodiversity and wildlife management into climate change policy frameworks in selected east and southern African countries.
The Rio+20 outcomes document, the Future We Want, enshrines green economy as one of the platforms to attain sustainable development and calls for measures that seek to address climate change and biodiversity management. This paper audits climate change policies from selected east and southern African countries to determine the extent to which climate change legislation mainstreams biodiversity and wildlife management. A scan of international, continental, regional and national climate change policies was conducted to assess whether they include biodiversity and/or wildlife management issues. The key finding is that many climate change policy-related documents, particularly the National Adaptation Programme of Actions (NAPAs), address threats to biodiversity and wildlife resources. However, international policies like the United Nations Framework Convention on Climate Change and Kyoto Protocol do not address the matter under deliberation. Regional climate change policies such as the East African Community, Common Market for Eastern and Southern Africa and African Union address biodiversity and/or wildlife issues whilst the Southern African Development Community region does not have a stand-alone policy for climate change. Progressive countries like Rwanda, Uganda, Tanzania and Zambia have recently put in place detailed NAPAs which are mainstream responsive strategies intended to address climate change adaptation in the wildlife sector.


The Regulatory Factor ZFHX3 Modifies Circadian Function in SCN via an AT Motif-Driven Axis.
We identified a dominant missense mutation in the SCN transcription factor Zfhx3, termed short circuit (Zfhx3(Sci)), which accelerates circadian locomotor rhythms in mice. ZFHX3 regulates transcription via direct interaction with predicted AT motifs in target genes. The mutant protein has a decreased ability to activate consensus AT motifs in vitro. Using RNA sequencing, we found minimal effects on core clock genes in Zfhx3(Sci/+) SCN, whereas the expression of neuropeptides critical for SCN intercellular signaling was significantly disturbed. Moreover, mutant ZFHX3 had a decreased ability to activate AT motifs in the promoters of these neuropeptide genes. Lentiviral transduction of SCN slices showed that the ZFHX3-mediated activation of AT motifs is circadian, with decreased amplitude and robustness of these oscillations in Zfhx3(Sci/+) SCN slices. In conclusion, by cloning Zfhx3(Sci), we have uncovered a circadian transcriptional axis that determines the period and robustness of behavioral and SCN molecular rhythms.


Estimating the population burden of lymphedema.
Lymphedema is a complex, regional edematous state that ensues when lymph transport is insufficient to maintain tissue homeostasis. The disorder is remarkably prevalent, but the population implications of lymphatic dysfunction are not well-studied. Prevalence estimates for lymphedema are relatively high, yet its prevalence is likely underestimated. The ability to estimate the burden of disease poses profound implications for current and future lymphedema patients, but the challenge to correctly surmise the incidence and prevalence of lymphedema is complex and the relevant medical literature is scanty. In the absence of the highly desired, prospectively designed and rigorously performed relevant epidemiologic studies, it is instructive to look at the existing studies of lymphedema disease burden. In the current review, the extant literature is examined in the context of the disease setting in which tissue edema is encountered. Incidence or prevalence estimates are provided or inferred, and, where feasible, the size of the subject population is also identified. It is extremely attractive to contemplate that future approaches will entail formal, prospectively designed studies to objectively quantitate incidence and prevalence statistics for individual categories, as well as for the global lymphedema population.


Serovars, bacteriophage types and antimicrobial sensitivities associated with salmonellosis in dogs in the UK (1954-2012).
Serovars and bacteriophage (phage) types were determined for 442 isolates of Salmonella enterica from dogs in the UK submitted to the Scottish Salmonella Reference Laboratory from 1954 to 2012. The most frequent serovars were Salmonella Typhimurium (196 isolates; 44.3 per cent), Dublin (40 isolates; 9.0 per cent), Enteritidis (28 isolates; 6.3 per cent), Montevideo (19 isolates; 4.3 per cent), Virchow (10 isolates; 2.3 per cent), Heidelberg (8 isolates; 1.8 per cent) and Derby (8 isolates; 1.8 per cent), along with 55 other recognised serovars among 127 other isolates, and six incompletely classified isolates. Serovars were frequently represented by strains commonly associated with poultry, cattle or pigs and their products. Among 196 Salmonella Typhimurium isolates from dogs, the most frequent phage types (definitive types) were the multiple antimicrobial-resistant strains DT104 (62 isolates), DT204c (18 isolates) and DT193 (8 isolates), along with antimicrobial sensitive wild finch strains DT40 (13 isolates) and DT56 variant (8 isolates). Eleven of 28 isolates of Salmonella Enteritidis were phage type 4. S enterica was frequently recovered from faecal or intestinal samples of dogs with diarrhoea, although many dogs had concurrent infection with other enteric pathogens. Salmonella Dublin was recovered from the brain and/or cerebrospinal fluid of two dogs with meningoencephalitis. Salmonella Kedougou was isolated from the joint fluid of a dog with septic arthritis. Salmonella Typhimurium and Salmonella Dublin were each recovered from the vaginas of bitches that had aborted. Isolates of Salmonella Enteritidis phage types 1, 4 and 8, Salmonella Typhimurium DT104, Salmonella Dublin and Salmonella Indiana were isolated from clinically healthy dogs in households where the same strains were recovered from human beings with diarrhoea. The pattern ampicillin-chloramphenicol-spectinomycin-streptomycin-sulfamethoxazole-tetracycline (ACSpSSuT) was the most frequent resistance phenotype and was observed in 44 (13.3 per cent) of 330 isolates. Dogs in the UK are exposed to a wide variety of serovars of S enterica, sometimes associated with clinical disease, and represent a zoonotic risk.


A Simple Silver Nanowire Patterning Method Based on Poly(Ethylene Glycol) Photolithography and Its Application for Soft Electronics.
Hydrogel-based flexible microelectrodes have garnered considerable attention recently for soft bioelectronic applications. We constructed silver nanowire (AgNW) micropatterns on various substrates, via a simple, cost-effective, and eco-friendly method without aggressive etching or lift-off processes. Polyethylene glycol (PEG) photolithography was employed to construct AgNW patterns with various shapes and sizes on the glass substrate. Based on a second hydrogel gelation process, AgNW patterns on glass substrate were directly transferred to the synthetic/natural hydrogel substrates. The resultant AgNW micropatterns on the hydrogel exhibited high conductivity (ca. 8.40 × 103 S cm-1) with low sheet resistance (7.51 ± 1.11 Ω/sq), excellent bending durability (increases in resistance of only ~3 and ~13% after 40 and 160 bending cycles, respectively), and good stability in wet conditions (an increase in resistance of only ~6% after 4 h). Considering both biocompatibility of hydrogel and high conductivity of AgNWs, we anticipate that the AgNW micropatterned hydrogels described here will be particularly valuable as highly efficient and mechanically stable microelectrodes for the development of next-generation bioelectronic devices, especially for implantable biomedical devices.


A global benchmark study using affinity-based biosensors.
To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.


A genome-wide association study of neuroticism in a population-based sample.
Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p < 10(-6)) and GPC6 showed suggestive evidence for interaction with age (p approximately = 10(-7)). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism.


Ginzburg-Landau theory of the liquid-solid interface and nucleation for hard spheres.
The Ginzburg-Landau free energy functional for hard spheres is constructed using the fundamental measure theory approach to density functional theory as a starting point. The functional is used to study the liquid-fcc solid planer interface and the properties of small solid clusters nucleating within a liquid. The surface tension for planer interfaces agrees well with simulation and it is found that the properties of the solid clusters are consistent with classical nucleation theory.


[Characteristics of clinical trials authorized in Peru: 1995-2012].
To identify main characteristics of clinical trials (CT) authorized by the National Institute of Health (INS) of Peru from 1995 to August 2012. Cross-sectional study, which reviewed all records of CT submitted for review and possible approval by INS, whose data are part of the Peruvian Registry of Clinical Trials. We performed a descriptive analysis of the states of the CT approval and other characteristics. 1475 clinical trials were assessed, of which 1255 (85.1%) were authorized. From 1 clinical trial officially registered in 1995, its quantity increased to 176 trials submitted in 2008, and then, declined to 128 in 2011. Among the approved CT, 64.1% was in Phase III. Oncology (22.4%), infectious diseases (15.5%) and endocrinology (12.7%) were the most studied specialties and a only 1.2% were for neglected tropical diseases. The oral hypoglycemic drugs, systemic antiviral and antineoplastic agents were the most studied investigational products. The transnational pharmaceutical industry was the main sponsor (87.1%) and executors (62.3%) of clinical trials were mostly in Lima. Clinical trials in Peru mainly focus on noncommunicable diseases and phase III studies. The pharmaceutical industry is the main sponsor. A very small number of authorized clinical trials in Peru were for neglected tropical diseases that shows little attention to the health problems in vulnerable populations.


Insight into the genetic components of community genetics: QTL mapping of insect association in a fast-growing forest tree.
Identifying genetic sequences underlying insect associations on forest trees will improve the understanding of community genetics on a broad scale. We tested for genomic regions associated with insects in hybrid poplar using quantitative trait loci (QTL) analyses conducted on data from a common garden experiment. The F2 offspring of a hybrid poplar (Populus trichocarpa x P. deltoides) cross were assessed for seven categories of insect leaf damage at two time points, June and August. Positive and negative correlations were detected among damage categories and between sampling times. For example, sap suckers on leaves in June were positively correlated with sap suckers on leaves (P<0.001) but negatively correlated with skeletonizer damage (P<0.01) in August. The seven forms of leaf damage were used as a proxy for seven functional groups of insect species. Significant variation in insect association occurred among the hybrid offspring, including transgressive segregation of susceptibility to damage. NMDS analyses revealed significant variation and modest broad-sense heritability in insect community structure among genets. QTL analyses identified 14 genomic regions across 9 linkage groups that correlated with insect association. We used three genomics tools to test for putative mechanisms underlying the QTL. First, shikimate-phenylpropanoid pathway genes co-located to 9 of the 13 QTL tested, consistent with the role of phenolic glycosides as defensive compounds. Second, two insect association QTL corresponded to genomic hotspots for leaf trait QTL as identified in previous studies, indicating that, in addition to biochemical attributes, leaf morphology may influence insect preference. Third, network analyses identified categories of gene models over-represented in QTL for certain damage types, providing direction for future functional studies. These results provide insight into the genetic components involved in insect community structure in a fast-growing forest tree.


[Morphological and immunological variation of Borrelia burgdorferi and diagnostic methods].
Diagnostic problems observed in patients infected with Borrelia burgdorferi are a significant impediment to therapeutic decision making. It appears that the pathogen is characterized by morphological and immunological variation in particular stages of development. The bacterium has the ability to morphologically transform into a cell wall deficient form of spheroplast, L-form, bleb-like spirochetes and round body/form cysts. It also has the ability to create biofilm, which is a major barrier to antibiotics. Bacteria are characterized by significant heterogeneity and antigen polymorphism, which greatly hampers the detailed definition of the pathogen, since the antibodies produced may differ significantly from the accepted patterns and also lead to cross reactions. The above conditions affect the reliability of diagnostic tests, especially screening, which may lead to wrong therapeutic decisions.


Protecting girls and women from harmful practices affecting their health: Are we making progress?
Since female genital mutilation (FGM) was first recognized internationally in 1958, it has now become widely accepted and anchored in international law that FGM is a violation of girls' and women's human rights. Declines in the practice, however, are slow overall, and continued work for its elimination requires action and investment at many levels. Where the practice has diminished, community action has been widespread and sustained. Governments, who are ultimately responsible for the eradication of FGM, must take many measures to outlaw the practice and protect girls' and women's rights, through legislation, policy, education, and resource allocation. Among the other key actors, health care professionals have a particularly important role in treating women and in preventing FGM by actively opposing any medicalization of the practice.


Sustenance and sustainability: maximizing the impact of school gardens on health outcomes.
School garden programmes have become popular action-oriented learning environments in many countries, often driven by converging priorities of environmental sustainability and healthful diets. Many of these programmes have assessed the impact on dietary intake, specifically fruit and vegetable intake, and related dietary behaviours, such as knowledge, preference, motivation, intention and self-efficacy to eat and prepare fruit and vegetables. The objective of the present study was twofold: (i) to review published garden-based programmes conducted in schools targeting dietary intake and/or determinants of dietary behaviour in children; and (ii) to identify similar strategies and components employed by these garden-based programmes. The review included thirteen studies that have examined the impact of garden-based programmes conducted in school, either during school hours or in after-school settings, on dietary behaviours in children (kindergarten through 8th grade students). Three of the reviewed studies did not have a comparison or control group and simply evaluated within-group changes after a garden intervention. None of the reviewed studies were randomized, but were assigned based on school's interest and timing of new school gardens being built. Out of the eleven programmes that examined dietary intake, six found that the programme resulted in increased vegetable intake, whereas four showed no effect. Seven of the eight studies that measured preference found that the programmes resulted in increased preference for vegetables. Gardening programmes also resulted in improved attitudes towards, willingness to taste, identification of and self-efficacy to prepare/cook fruit and vegetables. Similar strategies/components employed by the majority of the programmes included: 'hands on' curriculum, incorporation of a cooking component, providing the instructors, parental and stakeholder support, food provision and using the garden as the focal point for media promotion. Some of the garden programmes resulted in increased vegetable intake, which has positive implications for both environment sustainability and health-related outcomes. Further, the majority resulted in some improvement in behaviour determinants more generally. However, more research is warranted to understand how to achieve long-term improvements in dietary behaviours and how to sustain the garden-based programmes in schools.


Comparison of survival and heat resistance of Escherichia coli O121 and Salmonella in muffins.
This study was conducted to validate a simulated commercial baking process for plain muffins against E. coli O121 (isolated from the recent illness outbreak associated with flour), and compare the thermal inactivation parameters (D- and z-values) of cocktails of four isolates of E. coli O121 and three serovars of Salmonella (Newport, Typhimurium, and Senftenberg) in muffin batter. Flour samples were spray inoculated with the E. coli O121 or Salmonella cocktails, dried back to the pre-inoculation weight to achieve ~7 log10 CFU/g, and used to prepare muffin batter. For the muffin baking validation study using E. coli O121, muffin batter was baked at 375 °F (190.6 °C) oven temperature for 21 min followed by 30 min of ambient cooling. The E. coli O121 population decreased by >7 log10 CFU/g in muffins by 17 min of baking, and was completely eradicated after 21 min of baking and ambient cooling. The D-values of E. coli O121 and Salmonella cocktails in muffin batter at 60, 65 and 70 °C were 42.0 and 38.4, 7.5 and 7.2, and 0.4 and 0.5 min, respectively; whereas the z-values of E. coli O121 and Salmonella were 5.0 and 5.2 °C, respectively.


Single center experience of capsule endoscopy in patients with obscure gastrointestinal bleeding.
To identify optimum timing to maximize diagnostic yield by capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB). We identified patients who underwent CE at our institution from August 2003 to December 2009. Patient medical records were reviewed to determine type of OGIB (occult, overt), CE results and complications, and timing of CE with respect to onset of bleeding. Out of 385 patients investigated for OGIB, 284 (74%) had some lesion detected by CE. In 222 patients (58%), definite lesions were detected that could unequivocally explain OGIB. Small bowel ulcer/erosions secondary to Crohn's disease, tuberculosis or non-steroidal anti-inflammatory agent use were the commonest lesions detected. Patients with overt GI bleeding for < 48 h before CE had the highest diagnostic yield (87%). This was significantly greater (P < 0.05) compared to that in patients with overt bleeding prior to 48 h (68%), as well as those with occult OGIB (59%). We established the importance of early CE in management of OGIB. CE within 48 h of overt bleeding has the greatest potential for lesion detection.


Two different kinds of key peck in the pigeon: some properties of responses maintained by negative and positive response-reinforcer contingencies.
Pigeons emitted almost exclusively short-duration key pecks (shorter than 20 msec) when on negative automaintenance procedures, in which pecks prevented reinforcement. Peck durations under fixed-interval and fixed-ratio reinforcement schedules were generally two to five times longer than pecks under a negative automaintenance schedule. However, initial key pecks were of short duration, independent of procedure. The frequency of short-duration pecks was insensitive to differential reinforcement, while the frequency of long-duration pecks was sensitive to differential reinforcement. It is proposed that short-duration pecks arise from the pigeon's normal feeding pattern and are directly enhanced by food presentation, while long-duration pecks are controlled by the contingent effects of food presentation. The implications of the existence of two classes of pecks for the functional definition of operants and the separation of phylogenetic and ontogenetic sources of control of key pecking are discussed.


Pea Plants Show Risk Sensitivity.
Sensitivity to variability in resources has been documented in humans, primates, birds, and social insects, but the fit between empirical results and the predictions of risk sensitivity theory (RST), which aims to explain this sensitivity in adaptive terms, is weak [1]. RST predicts that agents should switch between risk proneness and risk aversion depending on state and circumstances, especially according to the richness of the least variable option [2]. Unrealistic assumptions about agents' information processing mechanisms and poor knowledge of the extent to which variability imposes specific selection in nature are strong candidates to explain the gap between theory and data. RST's rationale also applies to plants, where it has not hitherto been tested. Given the differences between animals' and plants' information processing mechanisms, such tests should help unravel the conflicts between theory and data. Measuring root growth allocation by split-root pea plants, we show that they favor variability when mean nutrient levels are low and the opposite when they are high, supporting the most widespread RST prediction. However, the combination of non-linear effects of nitrogen availability at local and systemic levels may explain some of these effects as a consequence of mechanisms not necessarily evolved to cope with variance [3, 4]. This resembles animal examples in which properties of perception and learning cause risk sensitivity even though they are not risk adaptations [5].


Stereotype content model across cultures: towards universal similarities and some differences.
The stereotype content model (SCM) proposes potentially universal principles of societal stereotypes and their relation to social structure. Here, the SCM reveals theoretically grounded, cross-cultural, cross-groups similarities and one difference across 10 non-US nations. Seven European (individualist) and three East Asian (collectivist) nations (N=1,028) support three hypothesized cross-cultural similarities: (a) perceived warmth and competence reliably differentiate societal group stereotypes; (b) many out-groups receive ambivalent stereotypes (high on one dimension; low on the other); and (c) high status groups stereotypically are competent, whereas competitive groups stereotypically lack warmth. Data uncover one consequential cross-cultural difference: (d) the more collectivist cultures do not locate reference groups (in-groups and societal prototype groups) in the most positive cluster (high-competence/high-warmth), unlike individualist cultures. This demonstrates out-group derogation without obvious reference-group favouritism. The SCM can serve as a pancultural tool for predicting group stereotypes from structural relations with other groups in society, and comparing across societies.


Evidence for the efficacy of a bioresonance method in smoking cessation: a pilot study.
Since the 1970s, MORA bioresonance therapy has globally been applied in the context of complementary medicine for various indications. In this regard, practitioners also report successful application in smoking cessation. The present study aims to verify these reports in a controlled study setting. In order to achieve the aforementioned objective, we subjected the bioresonance method to a prospective, placebo-controlled, double-blind, parallel-group study involving 190 smokers. In both study groups (placebo n = 95; active bioresonance group; n = 95) the course of treatment and study conditions were standardized. 1 week (77.2% vs. 54.8%), 2 weeks (62.4% vs. 34.4%), 1 month (51.1% vs. 28.6%), and 1 year (28.6% vs. 16.1%) after treatment, the success rate in the verum group differed significantly from the results in the placebo group. Also, the subjective health condition after treatment and subjective assessment of efficacy, polled after 1 week, were significantly more positive among participants in the active bioresonance therapy group than among those in the placebo group. Adverse side effects were not observed. According to the findings attained by this pilot study, bioresonance therapy is clinically effective in smoking cessation and does not show any adverse side effects.


Explaining nursing attrition through the experiences of return-to-practice students: a mixed-methods study.
Nurse shortage is an international issue that has adverse effects on health and the quality of care of whole populations. The study aimed to explore attrition experienced by return-to-practice students attending higher education institutions in England. A mixed-methods design, involving questionnaires (n=114) and in-depth interviews (n=20), was used. Just over half (52%) of respondents left nursing after ≥10 years. Most of these (84%) stayed in alternative employment during their break from nursing. There were two distinct reasons for leaving nursing: the inability to maintain a positive work/life balance and a lack of opportunity for career advancement while retaining nursing registration. Respondents reflected positively on their nursing experience yet frequently reported significant personal or professional incidents prompting their decision to leave. The reasons nurses leave are complex. Professional bodies and managers need to work together to address concerns many nurses have during their careers that lead to them deciding to leave the profession.


Chirped area coupled resonator optical waveguide gyroscope.
We study the transmission of an optical field through a rotating coupled resonator optical waveguide (CROW) in which the size of the ring resonators changes from one ring to the next. We focus on symmetric integer wavelength chirps of the circumference of the rings relative to the central ring in the array. The transfer matrix method is used to obtain the transmission as a function of the inertial rotation rate Ω resulting from the Sagnac effect. Chirping increases the slope of the oscillations in the transmission as a function of Ω, which can be exploited to further enhance the rotation sensitivity beyond that of a CROW with uniform resonators.


Improving the assembly speed, quality, and tunability of thin conductive multilayers.
While inhomogeneous thin conductive films have been sought after for their flexibility, transparency, and strength, poor control in the processing of these materials has restricted their application. The versatile layer-by-layer assembly technique allows greater control over film deposition, but even this has been hampered by the traditional dip-coating method. Here, we employ a fully automated spin-spray layer-by-layer system (SSLbL) to rapidly produce high-quality, tunable multilayer films. With bilayer deposition cycle times as low as 13 s (~50% of previously reported) and thorough characterization of film conductance in the near percolation region, we show that SSLbL permits nanolevel control over film growth and efficient formation of a conducting network not available with other methods of multilayer deposition. The multitude of variables from spray time, to spin rate, to active drying available with SSLbL makes films generated by this technique inherently more tunable and expands the opportunity for optimization and application of composite multilayers. A comparison of several polymer-CNT systems deposited by both spin-spray and dip-coating exemplifies the potential of SSLbL assembly to allow for rapid screening of multilayer films. Ultrathin polymer-CNT multilayers assembled by SSLbL were also evaluated as lithium-ion battery electrodes, emphasizing the practical application of this technique.


The India Local Initiatives Program: a model for expanding reproductive and child health services.
The India Local Initiatives Program adapted a model used in Indonesia and Bangladesh to implement the government's reproductive and child health strategy. From 1999 to 2003, three Indian nongovernmental organizations (NGOs) provided services for 784,000 people in four northern states. The program established health committees in 620 villages, recruited and trained 1,850 community health volunteers, and added 232 sites to extend government services. Using three strategies--demand creation, increased access to services, and local capacity building--the NGOs increased contraceptive-use rates by 78 percent, on average; child immunizations by 67 percent; and antenatal care by 78 percent among the populations served. Community resources--such as local health personnel, community-supplied clinic sites, and community drug funds--added 40 cents to every dollar provided by donors. This model proved to be a suitable platform upon which to build health-care service delivery and create behavioral change, and the NGOs quickly found ways to sustain and expand services.


Invasion pathway of the Ctenophore Mnemiopsis leidyi in the Mediterranean Sea.
Gelatinous zooplankton outbreaks have increased globally owing to a number of human-mediated factors, including food web alterations and species introductions. The invasive ctenophore Mnemiopsis leidyi entered the Black Sea in the early 1980s. The invasion was followed by the Azov, Caspian, Baltic and North Seas, and, most recently, the Mediterranean Sea. Previous studies identified two distinct invasion pathways of M. leidyi from its native range in the western Atlantic Ocean to Eurasia. However, the source of newly established populations in the Mediterranean Sea remains unclear. Here we build upon our previous study and investigate sequence variation in both mitochondrial (Cytochrome c Oxidase subunit I) and nuclear (Internal Transcribed Spacer) markers in M. leidyi, encompassing five native and 11 introduced populations, including four from the Mediterranean Sea. Extant genetic diversity in Mediterranean populations (n = 8, N a = 10) preclude the occurrence of a severe genetic bottleneck or founder effects in the initial colonizing population. Our mitochondrial and nuclear marker surveys revealed two possible pathways of introduction into Mediterranean Sea. In total, 17 haplotypes and 18 alleles were recovered from all surveyed populations. Haplotype and allelic diversity of Mediterranean populations were comparable to populations from which they were likely drawn. The distribution of genetic diversity and pattern of genetic differentiation suggest initial colonization of the Mediterranean from the Black-Azov Seas (pairwise F ST = 0.001-0.028). However, some haplotypes and alleles from the Mediterranean Sea were not detected from the well-sampled Black Sea, although they were found in Gulf of Mexico populations that were also genetically similar to those in the Mediterranean Sea (pairwise F ST = 0.010-0.032), raising the possibility of multiple invasion sources. Multiple introductions from a combination of Black Sea and native region sources could be facilitated by intense local and transcontinental shipping activity, respectively.


Achieving the tobacco endgame: evidence on the hardening hypothesis from repeated cross-sectional studies in New Zealand 2008-2014.
The hardening hypothesis proposes that as smoking prevalence declines the proportion of 'hardcore' or 'hardened' smokers will increase. The possible constructs of hardening include reduced motivation to quit, increased levels of addiction, increased levels of disadvantage and reduced quit rates among continuing smokers. Most previous studies have investigated only a single facet of the hypothesis. We used data from a national population monitor to test the hypothesis using measures across all four hardening constructs. We analysed data from a biennial population-based survey of New Zealand adults (aged 15 years+) from 2008 to 2014. Data were collected through face-to-face computer-assisted personal interviews. During a period of reducing smoking prevalence, there were no statistically significant changes in indicators of hardening including the proportion of smokers who were unmotivated to quit, unable to quit despite repeated attempts or receiving state benefits or on a low income. Quit rates did not change significantly over the study period. For 2014 versus 2008, the OR for recent (within last 1-12 months) quitting was 1.14 (95% CI 0.53 to 2.46) and for sustained (within previous 13-24 months) quitting was 1.88 (95% CI 0.78 to 4.54). This study provides evidence that robust tobacco control strategies that result in substantial declines in smoking prevalence are not accompanied by the hypothesised increase in 'hardcore' or 'hardened' smokers who are more addicted and less motivated and able to quit. The findings suggest that there is no need for substantial change in approach to achieve New Zealand's Smokefree 2025 goal on the grounds that the smoker population is becoming increasingly hardened.


Evaluating landscape options for corridor restoration between giant panda reserves.
The establishment of corridors can offset the negative effects of habitat fragmentation by connecting isolated habitat patches. However, the practical value of corridor planning is minimal if corridor identification is not based on reliable quantitative information about species-environment relationships. An example of this need for quantitative information is planning for giant panda conservation. Although the species has been the focus of intense conservation efforts for decades, most corridor projects remain hypothetical due to the lack of reliable quantitative researches at an appropriate spatial scale. In this paper, we evaluated a framework for giant panda forest corridor planning. We linked our field survey data with satellite imagery, and conducted species occupancy modelling to examine the habitat use of giant panda within the potential corridor area. We then conducted least-cost and circuit models to identify potential paths of dispersal across the landscape, and compared the predicted cost under current conditions and alternative conservation management options considered during corridor planning. We found that due to giant panda's association with areas of low elevation and flat terrain, human infrastructures in the same area have resulted in corridor fragmentation. We then identified areas with high potential to function as movement corridors, and our analysis of alternative conservation scenarios showed that both forest/bamboo restoration and automobile tunnel construction would significantly improve the effectiveness of corridor, while residence relocation would not significantly improve corridor effectiveness in comparison with the current condition. The framework has general value in any conservation activities that anticipate improving habitat connectivity in human modified landscapes. Specifically, our study suggested that, in this landscape, automobile tunnels are the best means to remove current barriers to giant panda movements caused by anthropogenic interferences.


Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia.
Effective host defense against bacterial infection is dependent upon the vigorous recruitment and activation of neutrophils and macrophages. We hypothesized that IL-10 is produced in the setting of bacterial pneumonia, and this cytokine may attenuate host defense by inhibiting the expression of important activating and chemotactic cytokines. CD-1 mice were challenged with either 30 microliters of saline or saline containing 10(3) CFUs of Klebsiella pneumoniae intratracheally (i.t.) and lungs were harvested at 8, 24, and 48 h. The i.t. inoculation with K. pneumoniae resulted in a 13-, 14-, and 8-fold increase in lung homogenate TNF, macrophage inflammatory protein-2 (MIP-2), and macrophage inflammatory protein-1 alpha (MIP-1 alpha) levels, respectively, as compared with control animals. In addition, we observed an increase in IL-10 mRNA and protein levels in lung homogenates, maximal at 48 h postinoculation. To establish the biologic relevance of IL-10 in Klebsiella pneumonia, we passively immunized CD-1 mice with 0.5 ml of rabbit anti-murine IL-10 serum or preimmune serum i.p. 2 h before i.t. administration of K. pneumoniae. Treatment of animals with anti-IL-10 serum resulted in increased levels of TNF, MIP-2, and MIP-1 alpha, respectively, within lung homogenates at 24 and 48 h, as compared with preimmune-treated animals. Furthermore, neutralization of IL-10 resulted in a significant decrease in K. pneumoniae CFU in both lung homogenates and plasma harvested at 48 h, as well as a significant increase in survival in these animals. Our studies indicate that 1) IL-10 is produced during Klebsiella pneumonia; and 2) inhibition of IL-10 bioactivity in vivo results in enhanced bacterial clearance, increased expression of proinflammatory cytokines, and prolonged survival.


Neurotensin-deficient mice show altered responses to antipsychotic drugs.
The peptide transmitter neurotensin (NT) exerts diverse neurochemical effects that resemble those seen after acute administration of antipsychotic drugs (APDs). These drugs also induce NT expression in the striatum; this and other convergent findings have led to the suggestion that NT may mediate some APD effects. Here, we demonstrate that the ability of the typical APD haloperidol to induce Fos expression in the dorsolateral striatum is markedly attenuated in NT-null mutant mice. The induction of Fos and NT in the dorsolateral striatum in response to typical, but not atypical, APDs has led to the hypothesis that the increased expression of these proteins is mechanistically related to the production of extrapyramidal side effects (EPS). However, we found that catalepsy, which is thought to reflect the EPS of typical APDs, is unaffected in NT-null mutant mice, suggesting that NT does not contribute to the generation of EPS. We conclude that NT is required for haloperidol-elicited activation of a specific population of striatal neurons but not haloperidol-induced catalepsy. These results are consistent with the hypothesis that endogenous NT mediates a specific subset of APD actions.


Sense of coherence in Chinese and German students.
Mental health and salutogenesis are important topics at universities in China and Germany where heightening stress levels in students can be observed. The aim of this article is to determine the profile of the salutogenic concept, sense of coherence (SOC), in Chinese and German students to provide new insights into SOC and mental health in Chinese and German students in higher education institutions (HEIs). The study was carried out at universities in China and Germany. A non-experimental, cross-sectional, survey-based research design and convenience sampling was utilised to obtain the sample (n = 356). The sample was derived at a selected Chinese (n = 255) and a selected German university (n = 101). Data were gathered using the 7-point Likert SOC dimension scales based on the Life-Orientation Questionnaire (LOQ) research instrument. The internal consistency levels of the SOC sub-scales were of acceptable levels. Descriptive and inferential statistics were used to analyse the data. Cronbach's alpha coefficients were calculated to determine the reliability of the LOQ research instrument. General linear modelling techniques. The results showed the Chinese students scored significantly lower in all three SOC scales than the German students, with the largest practical significant difference in the sub-score of meaningfulness. In general, female Chinese and German students scored higher than their male counterparts. No significant differences could be found between German female and male, and Chinese female and male students. Conclusions and recommendations for future research and HEI practice are provided.


Lubricating conditions: effects on friction between orthodontic brackets and archwires with different cross-sections.
This study investigated the effect of the condition of lubrication on the friction between brackets and NiTi archwires of different rounded cross-sections. Brackets (Roth, GAC) were affixed to a device connected to a universal testing machine into which segments of archwire were placed (NiTi, Nitinol, GAC) with cross-sections of 0.012-in, 0.016-in and 0.020-in. Once the wire was in the bracket slot, the following lubricants were applied: human saliva (HS: positive control), distilled water (DI), mucin-based (MUC) or carboxymethylcellulose-based (CMC) artificial saliva. In the negative control group, no lubricant was used. The combination between the wire cross-sections and the lubrication condition generated 15 groups with 15 samples each. Data were submitted to two-way analysis of variance and Tukey's test. There was no significant interaction between the wire cross-section and the condition of lubrication (p= 0.901). Irrespective of whether lubricants were used or not, there was a significant increase in friction with an increase in the cross-section of the wire (p< 0.001). For any wire, the group tested in the presence of MUC was not different from that in which HS was applied. On the other hand, when the application of lubricants was suppressed, significantly higher friction values were observed. The CMC group and the DI group demonstrated intermediate behavior. Friction increased with the increase of the cross-section of the NiTi archwire, but regardless of the archwire, friction with MUC artificial saliva was similar to that of HS and lower than in dry conditions.


Lectin receptors in the human cornea.
Five different biotin labeled lectins, Concanavalin-A (Con A), wheat germ agglutinin (WGA), Ricinus communis agglutinin I (RCA1), Ulex europaeus agglutinin (UEA1), and soybean agglutinin (SBA) were used to study lectin receptors on formalin-fixed paraffin embedded human corneas. Con A stained the cytoplasm, cell, and nuclear membranes of the epithelial cells and stained the stroma diffusely. WGA stained the superficial epithelial cells, the epithelial cell membranes, and the keratocytes of the stroma. SBA did not react with any of the corneal layers. RCA1 heavily stained the keratocytes but did not stain the epithelium. UEA1 lightly stained the epithelial cell cytoplasm and interstitial stroma. All staining reactions could be abolished by omission of the lectin or by the use of the appropriate inhibitory sugar. The lectin binding patterns reported here provide a means for further investigation of carbohydrate structures in the human cornea in both normal and disease states.


Robust neurite extension following exogenous electrical stimulation within single walled carbon nanotube-composite hydrogels.
The use of exogenous electrical stimulation to promote nerve regeneration has achieved only limited success. Conditions impeding optimized outgrowth may arise from inadequate stimulus presentation due to differences in injury geometry or signal attenuation. Implantation of an electrically-conductive biomaterial may mitigate this attenuation and provide a more reproducible signal. In this study, a conductive nanofiller (single-walled carbon nanotubes [SWCNT]) was selected as one possible material to manipulate the bulk electrical properties of a collagen type I-10% Matrigel™ composite hydrogel. Neurite outgrowth within hydrogels (SWCNT or nanofiller-free controls) was characterized to determine if: (1) nanofillers influence neurite extension and (2) electrical stimulation of the nanofiller composite hydrogel enhances neurite outgrowth. Increased SWCNT loading (10-100-μg/mL) resulted in greater bulk conductivity (up to 1.7-fold) with no significant changes to elastic modulus. Neurite outgrowth increased 3.3-fold in 20-μg/mL SWCNT loaded biomaterials relative to the nanofiller-free control. Electrical stimulation promoted greater outgrowth (2.9-fold) within SWCNT-free control. The concurrent presentation of electrical stimulation and SWCNT-loaded biomaterials resulted in a 7.0-fold increase in outgrowth relative to the unstimulated, nanofiller-free controls. Local glia residing within the DRG likely contribute, in part, to the observed increases in outgrowth; but it is unknown which specific nanofiller properties influence neurite extension. Characterization of neuronal behavior in model systems, such as those described here, will aid the rational development of biomaterials as well as the appropriate delivery of electrical stimuli to support nerve repair. Novel biomedical devices delivering electrical stimulation are being developed to mitigate symptoms of Parkinson's, treat drug-resistant depression, control movement or enhance verve regeneration. Carbon nanotubes and other novel materials are being explored for novel nano-neuro devices based on their unique properties. Neuronal growth on carbon nanotubes has been studied in 2D since the early 2000s demonstrating increased outgrowth, synapse formation and network activity. In this work, single-walled carbon nanotubes were selected as one possible electrically-conductive material, dispersed within a 3D hydrogel containing primary neurons; extending previous 2D work to 3D to evaluate outgrowth within nanomaterial composites with electrical stimulation. This is the first study to our knowledge that stimulates neurons in 3D composite nanomaterial-laden hydrogels. Examination of electrically conductive biomaterials may serve to promote regrowth following injury or in long term stimulation.


Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results.
Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke. Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results- In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32). This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.


Influence of different organic waste materials on the transformation of nitrogen in soils.
Organic waste materials like crop residues, well-decomposed cow dung, composts, and other rural and urban wastes are considered highly useful resources in enhancing soil fertility and also in build-up of soil organic matter. Organic matter decomposition provides plant nutrients in soil, which in turn increases crop productivity. Availability of nutrients and nitrogen (N) and phosphorus from organic waste materials is dependent upon the nature of organic residues, climatic conditions, and soil moisture activity. Keeping these factors in view, the present investigation was undertaken to study the transformation of N from different organic waste materials in two contrasting soils from an eastern India, subtropical region. The results showed that the amounts of ammoniacal-N (NH4-N), nitrate-N (NO3-N), hydrolysable N (HL-N), and nonhydrolysable (NHL-N) were increased for up to 60 days of soil submergence and increased further with the increase (1% by weight of soil) of organic residue application. Considering the effect of various organic waste materials, it was found that the amounts of NH4-N, NO3-N, HL-N, and NHL-N were higher with the application of groundnut hull as compared to wheat straw and potato skin, which may be due to relatively narrow carbon:N ratio of groundnut (22:43) than that of wheat straw (62:84) and potato skin (71:32); however, the results showed that the release of NH4-N, NO3-N, HL-N, and NHL-N was in the order of groundnut hull > wheat straw > potato skin.


Absence of Stat1 in donor CD4⁺ T cells promotes the expansion of Tregs and reduces graft-versus-host disease in mice.
STAT1 is the main signal transducer for type I and II IFNs and plays a central role in the regulation of innate and adaptive immune responses. We used Stat1-deficient mice to test the role of donor Stat1 in MHC-matched minor histocompatibility antigen-mismatched (mHA-mismatched) and fully MHC-mismatched models of bone marrow transplantation. Lack of Stat1 in donor splenocytes reduced graft-versus-host disease (GVHD) in both immunogenetic disparities, leading to substantially attenuated morbidity and mortality. Donor Stat1 deficiency resulted in reduced alloantigen-induced activation and expansion of donor T cells and correlated with the expansion of CD4+CD25+Foxp3+ Tregs in vivo. This expansion of Tregs was further confirmed by studies showing that Stat1 deficiency promoted the proliferation, while inhibiting the apoptosis, of natural Tregs, and that absence of Stat1 enhanced the induction of inducible Tregs both in vitro and in vivo. Ex vivo expanded Stat1-/- Tregs were superior to wild-type Tregs in suppressing alloantigen-driven expansion of T cells in vitro and in inhibiting the development of GVHD. These observations demonstrate that Stat1 is a regulator of Tregs and that targeting Stat1 in CD4+ T cells may facilitate in vitro and in vivo expansion of Tregs for therapeutic use.


A study of underreporting of Down's syndrome on birth certificates in an Ohio County, 1970-78.
In a previous statewide assessment in Ohio of the percentage reporting of Down's syndrome (DS) on birth certificates, it was found that 33.9 percent of the cases chromosomally analyzed were so recorded. The objectives of this study were to gain a greater understanding of the basis of this low reporting percentage by concentrating on Hamilton County births only, to compare these percentages among hospitals in the county, and to determine the commonality of their causes. Since it was anticipated that both a thorough search of hospital records and access to chromosome analysis records would provide essentially complete ascertainment of DS births in the county during 1970-78, the data were also used to test the validity of chromosome analysis as a sampling procedure in estimating the total number of DS births by means of the Lincoln-Peterson capturerecapture method.The percentage of reporting of DS on the birth certificates by hospital ranged from 0.0 to 57.1, with a mean of 26.0 for the 6 hospitals within the county. Although variation among some hospitals was statistically significant, three of the six hospitals had zero percent reporting. The explanation for these low reporting percentages was fundamentally similar for all hospitals-a communications flow problem, produced by poor timing and use of the wrong sources of available information. The only data typically available to the birth certificate clerk were derived from the labor and delivery sheet, the form with the worst reporting percentage of DS of any in the medical record. On the other hand, by the time of discharge, 92.5 percent of the cases had either been definitely diagnosed as DS and were recorded on the face sheet or were entered as "chromosome analysis pending" in the file.The use of the chromosome analysis data gave an estimate of total DS births (N = 201 +/- 34) statistically consistent with the total observed, thereby providing support for this estimation procedure. Annual incidence rates for DS were also calculated for 1970-78, with a total incidence rate for the 9-year period of 1.14 per 1,000 live births.


Relationship between orofacial function, dentofacial morphology, and bite force in young subjects.
The aim was to evaluate the relationship between orofacial function, dentofacial morphology, and bite force in young subjects. Three hundred and sixteen subjects were divided according to dentition stage (early, intermediate, and late mixed and permanent dentition). Orofacial function was screened using the Nordic Orofacial Test-Screening (NOT-S). Orthodontic treatment need, bite force, lateral and frontal craniofacial dimensions and presence of sleep bruxism were also assessed. The results were submitted to descriptive statistics, normality and correlation tests, analysis of variance, and multiple linear regression to test the relationship between NOT-S scores and the studied independent variables. The variance of NOT-S scores between groups was not significant. The evaluation of the variables that significantly contributed to NOT-S scores variation showed that age and presence of bruxism related to higher NOT-S total scores, while the increase in overbite measurement and presence of closed lip posture related to lower scores. Bite force did not show a significant relationship with scores of orofacial dysfunction. No significant correlations between craniofacial dimensions and NOT-S scores were observed. Age and sleep bruxism were related to higher NOT-S scores, while the increase in overbite measurement and closed lip posture contributed to lower scores of orofacial dysfunction.


Intracellular Leishmania amazonensis amastigotes internalize and degrade MHC class II molecules of their host cells.
In their amastigote stage, Leishmania live in mammalian macrophages within parasitophorous vacuoles (PV), organelles of phagolysosomal origin that, in macrophages activated with IFN-gamma, contain major histocompatibility complex (MHC) class II molecules apparently devoid of invariant chains. We have now studied the fate of PV-associated class II molecules in mouse bone marrow-derived macrophages infected with L. amazonensis amastigotes using immunocytochemical and biochemical approaches. We have found that at least a part of these class II molecules was internalized by amastigotes and reached structures very often located in their posterior poles. This process was much more obvious if infected macrophages were incubated with protease inhibitors like antipain, chymostatin, Z-Phe-AlaCHN2 and Z-Phe-PheCHN2, or if amastigotes were pre-treated with the irreversible cysteine protease inhibitor Z-Phe-AlaCHN2 before infection, clearly indicating that amastigotes also degraded the internalized class II molecules. Study of infected macrophage cryosections by immuno-electron microscopy allowed the identification of the class II-positive structures in amastigotes as the lysosome-like organelles known as megasomes. Other PV membrane components like the prelysosomal/lysosomal glycoproteins Igp110, Igp120 and macrosialin could not be detected in megasomes of amastigotes even after treatment of macrophages with protease inhibitors, suggesting the involvement of some specific mechanism(s) for the internalization of class II molecules. Interestingly, after treatment of infected macrophages with various protease inhibitors (antipain, leupeptin, E-64, Z-Phe-AlaCHN2, Z-Phe-PheCHN2), PV membrane as well as megasomes of amastigotes become positive for invariant chains. A quantitative analysis of amastigote-associated class II molecules based on enzyme immunoassays showed that: (a) amastigotes extracted from macrophages treated with both IFN-gamma and antipain or Z-Phe-AlaCHN2 contained a much greater amount of class II than amastigotes extracted from macrophages treated with IFN-gamma alone; (b) class II molecules associated with the former were mainly intracellular and, at least some of them, were complexed with invariant chains or fragments of invariant chains; (c) amastigotes pre-incubated with Z-Phe-AlaCHN2 before infection accumulated a greater amount of intracellular class II than amastigotes pre-incubated without inhibitor, clearly indicating that the blockade of parasite cysteine proteases was sufficient to enhance the pool of these molecules within megasomes. On the whole, these data are consistent with the idea that class II molecules reaching PV are newly synthesized and still complexed with intact invariant chains or with partially degraded invariant chains.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of sevoflurane on cerebral perfusion pressure in patients with internal hydrocephalus.
Due to its confirmed neuroprotective properties, sevoflurane is one of a few anaesthetics used for neuroanaesthesia. Its effects on the cerebral and systemic circulations may be of particular importance in patientswith intracranial pathology. This study aimed to evaluate the effect of sevoflurane at concentrations lower than 1 MAC on cerebral perfusion pressure (CPP) in patients with internal hydrocephalus. The study was conducted on14 patients with internal hydrocephalus, who underwent ventriculo-peritoneal shunt implantation. After inserting the catheter into the lateral cerebral ventricle, sevoflurane, at 1.1 and 2.2 vol%, was initiated at two successive 15-minute intervals. The intracranial pressure (ICP) was continuously measured; special attention was focused on the values prior to and at the end of each observation period. The following parameters were monitored: mean arterial pressure (MAP), CPP, heart rate, end-tidal CO₂ concentration, core body temperature, and the inspiratory and end-expiratory concentrations of sevoflurane. The HR and MAP decreased during successive observation intervals compared to baseline values. Likewise, the CPP decreased from 75.6 ± 2.8 mm Hg to 72.2 ± 2.6 mm Hg to 70.2 ± 0.8 mm Hg. The baseline value for ICP was 16.3 ± 0.6 mm Hg and increased to 17.7 ± 0.8 and 18.9 ± 0.5 mm Hg during the next observation periods. Sevoflurane administered ata concentration below 1MAC to patients with internal hydrocephalus increases the ICP and decreases the MAP, which leads to adecrease in CPP. The CPP decrease is more dependent on depressing the systemic circulatory system than an increased ICP.


International law's effects on health and its social determinants: protocol for a systematic review, meta-analysis, and meta-regression analysis.
In recent years, there have been numerous calls for global institutions to develop and enforce new international laws. International laws are, however, often blunt instruments with many uncertain benefits, costs, risks of harm, and trade-offs. Thus, they are probably not always appropriate solutions to global health challenges. Given these uncertainties and international law's potential importance for improving global health, the paucity of synthesized evidence addressing whether international laws achieve their intended effects or whether they are superior in comparison to other approaches is problematic. Ten electronic bibliographic databases were searched using predefined search strategies, including MEDLINE, Global Health, CINAHL, Applied Social Sciences Index and Abstracts, Dissertations and Theses, International Bibliography of Social Sciences, International Political Science Abstracts, Social Sciences Abstracts, Social Sciences Citation Index, PAIS International, and Worldwide Political Science Abstracts. Two reviewers will independently screen titles and abstracts using predefined inclusion criteria. Pairs of reviewers will then independently screen the full-text of articles for inclusion using predefined inclusion criteria and then independently extract data and assess risk of bias for included studies. Where feasible, results will be pooled through subgroup analyses, meta-analyses, and meta-regression techniques. The findings of this review will contribute to a better understanding of the expected benefits and possible harms of using international law to address different kinds of problems, thereby providing important evidence-informed guidance on when and how it can be effectively introduced and implemented by countries and global institutions. PROSPERO CRD42015019830.


Ridge-penalized adaptive Mantel test and its application in imaging genetics.
We propose a ridge-penalized adaptive Mantel test (AdaMant) for evaluating the association of two high-dimensional sets of features. By introducing a ridge penalty, AdaMant tests the association across many metrics simultaneously. We demonstrate how ridge penalization bridges Euclidean and Mahalanobis distances and their corresponding linear models from the perspective of association measurement and testing. This result is not only theoretically interesting but also has important implications in penalized hypothesis testing, especially in high-dimensional settings such as imaging genetics. Applying the proposed method to an imaging genetic study of visual working memory in healthy adults, we identified interesting associations of brain connectivity (measured by electroencephalogram coherence) with selected genetic features.


Analysis of the Causes of Failed Antireflux Surgery and the Principles of Treatment: A Review.
Although the diagnostic evaluation and technical elements for a successful laparoscopic fundoplication have been clearly identified, 10% to 20% of patients will eventually experience recurrence of their symptoms. The management of patients who fail antireflux surgery is complex and not well codified. To provide an evidence- and experience-based analysis of the causes of failed antireflux surgery and to underscore the principles of treatment. PubMed was searched for articles published between 1980 and 2014. The search terms included were the following: heartburn, regurgitation, dysphagia, gastroesophageal reflux disease, cough, aspiration, laryngitis, GERD, GORD, endoscopy, manometry, pH monitoring, proton pump inhibitors, and Nissen fundoplication. Before planning therapy, a careful workup is necessary to determine whether the symptoms are due to recurrent reflux and to understand what caused the recurrence. Subsequently, therapy needs to be individualized based on the symptoms and on the findings of the workup. In some patients, a nonesophageal cause will be identified. Among patients with recurrent reflux, some will do well with acid-reducing medications and others will need another operation. Laparoscopic antireflux surgery is a very effective and long-lasting treatment for gastroesophageal reflux disease. Its success is based on a careful preoperative evaluation and on the performance of a fundoplication that respects the key technical elements. Patients who are still symptomatic postoperatively must be thoroughly evaluated to identify the cause of failure, and treatment must be individualized.