Exercise program for wheelchair activity.
Poor physical fitness of wheelchair-dependent individuals may result in excessive cardiorespiratory responses during locomotion. The purpose of this study was to develop and implement an interval training program (ITP) incorporating wheelchair ergometer (WERG) exercise to improve fitness for wheelchair activity. Of thirteen able-bodied female volunteers, seven were selected to participate in a 5-week ITP, while the remainder served as sedentary controls. Both the exercise training (ET) group and the sedentary control (SC) group completed a standardized fitness test on the WERG before (pre-test) and after (post-test) the 5-week period. Following the ITP, submaximal heart rate, pulmonary ventilation and oxygen uptake responses of the ET group were generally found to be significantly lower during the post-test. These improvements in WERG exercise performance were not observed in the SC group. The ITP may have contributed to adaptations of upper body muscles, improved cardiorespiratory function, and/or a higher level of skill for wheelchair propulsion. We conclude that applying the concepts of interval training to wheelchair exercise may substantially improve the performance and fitness characteristics of wheelchair users. This could reduce the relative stresses of wheelchair locomotion and lead to a higher level of rehabilitation.


Commissioning and benchmarking a 3D dosimetry system for clinical use.
A 3D dosimetry system is described which consists of two parts: a radiochromic plastic dosimeter PRESAGE (which responds to absorbed dose with a linear change in optical-density) and the Duke large-field-of-view optical-CT scanner (DLOS). The DLOS/PRESAGE system has recently been commissioned and benchmarked for clinical use and, in particular, for verification and commissioning of complex radiation treatments. DLOS commissioning involved determining the dynamic range, spatial resolution, noise, temporal, and other characteristics of the light source and imaging components. Benchmarking tests were performed on the combined DLOS/PRESAGE system to establish baseline dosimetric performance. The tests consisted of delivering simple radiation treatments to PRESAGE dosimeters, and comparing the measured 3D relative dose distributions with the known gold standard. The gold standard distribution was obtained from machine beam-data or the treatment planning system (TPS). All studies used standardized procedures to ensure consistency. For commissioning, isotropic spatial resolution was submillimeter (MTF > 0.5 for frequencies of 1.5 lp/mm) and the dynamic range was -60 dB. Flood field uniformity was within 10% and stable after 45 min of warm-up. Stray-light is small, due to telecentricity, but even the residual can be removed through deconvolution by a point-spread-function. For benchmarking, the mean 3D passing NDD (normalized dose distribution) rate (3%, 3mm, 5% dose threshold) over the benchmark data sets was 97.3% +/- 0.6% (range 96%-98%), which is on par with other planar dosimeters used in external beam radiation therapy indicating excellent agreement. Noise was low at < 2% of maximum dose (4-12 Gy) for 2 mm reconstructions. The telecentric design was critical to enabling fast imaging with minimal stray-light artifacts. This work presents the first comprehensive benchmarking of a 3D dosimetry system for clinical use. The DLOS/PRESAGE benchmark tests show consistently good agreement to simple known distributions. The system produces accurate isotropic 2 mm dose data over clinical volumes (e.g., 16 cm diameter phantoms, 12 cm height), in under 15 min. It represents a uniquely useful and versatile new tool for commissioning and verification of complex therapy treatments.


Outcome methods used in clinical studies of Chiari malformation Type I: a systematic review.
Chiari malformation Type I (CM-I) is a common and often debilitating neurological disease. Efforts to improve treatment of CM-I are impeded by inconsistent and limited methods of evaluating clinical outcomes. To understand current approaches and lay a foundation for future research, the authors conducted a systematic review of the methods used in original published research articles to evaluate clinical outcomes in patients treated for CM-I. The authors searched PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov , and Cochrane databases to identify publications between January 2003 and August 2013 that met the following criteria: 1) reported clinical outcomes in patients treated for CM-I; 2) were original research articles; 3) included at least 10 patients or, if a comparative study, at least 5 patients per group; and 4) were restricted to patients with CM-I. Among the 74 papers meeting inclusion criteria, there was wide variation in the outcome methods used. However, all approaches were broadly grouped into 3 categories: 1) "gestalt" impression of overall symptomatic improvement (n=45 papers); 2) postoperative change in specific signs or symptoms (n=20); or 3) results of various standardized assessment scales (n=22). Among standardized scales, 11 general function measures were used, compared with 6 disease-specific tools. Only 3 papers used scales validated in patients with CM-I. To facilitate a uniform comparison of these heterogeneous approaches, the authors appraised articles in multiple domains defined a priori as integral to reporting clinical outcomes in CM-I. Notably, only 7 articles incorporated patient-response instruments when reporting outcome, and only 22 articles explicitly assessed quality of life. The methods used to evaluate clinical outcomes in CM-I are inconsistent and frequently not comparable, complicating efforts to analyze results across studies. Development, validation, and incorporation of a small number of disease-specific patient-based instruments will improve the quality of research and care of CM-I patients.


Circulating genotypes of Leptospira in French Polynesia : An 9-year molecular epidemiology surveillance follow-up study.
Leptospirosis is a widespread zoonosis with global impact, particularly among vulnerable populations in resource-poor settings in tropical countries. Rodents have been considered to be the main reservoir of the disease; however, a wide variety of mammals can act as hosts as well. Here we examine the genetic diversity of Leptospira strains from biological samples of patients and animals in French Polynesia (FP) from 2011 to 2019. From 2011 to 2019, we have collected 444 blood samples from patients diagnosed as having leptospirosis. The limited volume of clinical material and low amount of leptospiral DNA in blood samples led us to develop a nested PCR targeting the secY locus that enabled us to amplify and sequence 244 samples (55%). In addition, 20 Leptospira strains recovered from the blood of patients from 2002 to 2011 were sequenced and fully characterized at the serogroup level and used as reference strains for the association of different phylogenetic branches with respective serogroups. The secY sequences were compared with publicly available sequences from patients and animal reservoirs in FP (n = 79). We identified rats as the main source of infection for L. borgpetersenii serogroup Ballum and L. interrogans serogroup Icterohaemorrhagiae, dogs as the main source of infection for L. interrogans serogroup Australis, and farm pigs as the main source of infection for L. interrogans serogroups Pomona or Canicola. L. interrogans was associated with the most severe infections with 10 and 5 fatal cases due to serogroups Icterohaemorrhagiae and Australis, respectively. Mortality was significantly associated with older age (p-value < 0.001). We described the population dynamics of leptospires circulating among patients in FP, including two patients who were reinfected with unrelated Leptospira genotypes, and clarified the local role of the animal reservoirs in the transmission route of leptospirosis to humans. Routine Leptospira genotyping directly on biological samples should allow the epidemiological follow-up of circulating strains and assess the impact of control interventions on disease transmission.


State coercion, moral attitudes, and tax compliance: Evidence from a national factorial survey experiment of income tax evasion.
Why do some people comply with their obligation to pay taxes while others do not? Scholars of tax behavior, particularly economists and political scientists, have relied on models of state coercion and state reciprocity to answer this question. Neither state coercion nor state reciprocity, however, sufficiently account for individuals who voluntarily comply with their tax obligations to the state. We offer a third explanation, derived from the new sociology of morality and moral psychology, suggesting that two types of moral attitudes (moral imperatives and moral alignment) affect tax compliance. Using a factorial survey experiment of income tax evasion and a survey questionnaire administered to a nationally representative random sample of U.S. adults, we provide a systematic test of the three different models of tax compliance. The results yield strong support for moral attitudes (both moral imperatives and moral alignment) and state coercion, but little support for state reciprocity. We review the implications of our findings in the discussion and conclusion.


Rapid effects of 17beta-estradiol on TRPV5 epithelial Ca2+ channels in rat renal cells.
The renal distal tubules and collecting ducts play a key role in the control of electrolyte and fluid homeostasis. The discovery of highly calcium selective channels, Transient Receptor Potential Vanilloid 5 (TRPV5) of the TRP superfamily, has clarified the nature of the calcium entry channels. It has been proposed that this channel mediates the critical Ca(2+) entry step in transcellular Ca(2+) re-absorption in the kidney. The regulation of transmembrane Ca(2+) flux through TRPV5 is of particular importance for whole body calcium homeostasis.In this study, we provide evidence that the TRPV5 channel is present in rat cortical collecting duct (RCCD(2)) cells at mRNA and protein levels. We demonstrate that 17beta-estradiol (E(2)) is involved in the regulation of Ca(2+) influx in these cells via the epithelial Ca(2+) channels TRPV5. By combining whole-cell patch-clamp and Ca(2+)-imaging techniques, we have characterized the electrophysiological properties of the TRPV5 channel and showed that treatment with 20-50nM E(2) rapidly (<5min) induced a transient increase in inward whole-cell currents and intracellular Ca(2+) via TRPV5 channels. This rise was significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV5.These data demonstrate for the first time, a novel rapid modulation of endogenously expressed TRPV5 channels by E(2) in kidney cells. Furthermore, the results suggest calcitropic effects of E(2). The results are discussed in relation to present concepts of non-genomic actions of E(2) in Ca(2+) homeostasis.


[A clinico-pathological comparison between Henoch-Schonlein purpura nephritis and IgA nephropathy in children].
To study the difference in clinico-pathological features between IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN) in children. The medical data of 103 children with HSPN and 61 children with IgAN were retrospectively studied. There were no significant differences in age, sex and disease course between the HSPN and IgAN groups (P>0.05). Clinical classification demonstrated that more severe conditions were found in the IgAN group than in the HSPN group and gross hematuria was more common in the IgAN group (P<0.05). Serum creatinine and cholesterol levels were higher in the IgAN group than in the HSPN group (P<0.05). Fibrinogen-related antigen deposition was more common in the HSPN group, while complement 3(C3) deposition was more common in the IgAN group. Interstitial fibrosis, tubular casts and tubular inflammatory infiltration were also more common in the IgAN group (P<0.05). Significant clinico-pathological differences can be found between HSPN and IgAN in children, and these differences do not support a one disease entity hypothesis.


Revisiting epiglottitis: a protocol--the value of lateral neck radiographs.
A retrospective review was done on the medical records (March 1986 through December 1989) of patients referred to Pittsburgh Children's Hospital with the presumptive diagnosis of epiglottitis. Data obtained included age, final diagnosis, referring physician's radiographic evaluation/interpretation, procedures (intubation, IV administered, aerosol, cultures obtained), transport times, and long-term morbidity and mortality. The diagnostic value of lateral neck radiographs was analyzed. Lateral neck radiographs were found to be of little value in the primary evaluation of epiglottitis. Rather, skilled personnel, using an established protocol, did limit morbidity and mortality in patients with symptoms consistent with epiglottitis. All medical centers should develop a protocol for management of patients presenting with symptoms suggestive of epiglottitis.


Upper Limb Outcome Measures Used in Stroke Rehabilitation Studies: A Systematic Literature Review.
Establishing which upper limb outcome measures are most commonly used in stroke studies may help in improving consensus among scientists and clinicians. In this study we aimed to identify the most commonly used upper limb outcome measures in intervention studies after stroke and to describe domains covered according to ICF, how measures are combined, and how their use varies geographically and over time. Pubmed, CinHAL, and PeDRO databases were searched for upper limb intervention studies in stroke according to PRISMA guidelines and477 studies were included. In studies 48different outcome measures were found. Only 15 of these outcome measures were used in more than 5% of the studies. The Fugl-Meyer Test (FMT)was the most commonly used measure (in 36% of studies). Commonly used measures covered ICF domains of body function and activity to varying extents. Most studies (72%) combined multiple outcome measures: the FMT was often combined with the Motor Activity Log (MAL), the Wolf Motor Function Test and the Action Research Arm Test, but infrequently combined with the Motor Assessment Scale or the Nine Hole Peg Test. Key components of manual dexterity such as selective finger movements were rarely measured. Frequency of use increased over a twelve-year period for the FMT and for assessments of kinematics, whereas other measures, such as the MAL and the Jebsen Taylor Hand Test showed decreased use over time. Use varied largely between countries showing low international consensus. The results showed a large diversity of outcome measures used across studies. However, a growing number of studies used the FMT, a neurological test with good psychometric properties. For thorough assessment the FMT needs to be combined with functional measures. These findings illustrate the need for strategies to build international consensus on appropriate outcome measures for upper limb function after stroke.


BEPITOPE: predicting the location of continuous epitopes and patterns in proteins.
In growing need of obtaining highly specific monoclonal antibodies against novel proteins, we developed new functions implemented in the program BEPITOPE to predict continuous protein epitopes. This program not only can compute, combine, display and print prediction profiles, but also provides a list of suggested linear peptides to be synthesized. Novel facilities incorporated in BEPITOPE include the treatment of a whole genome, the search for a user-defined pattern, and the combination of prediction to pattern profiles. This latter approach is useful to remove unwanted predictions such as those including glycosylation sites.


Molecular imaging of embryonic stem cell misbehavior and suicide gene ablation.
Numerous studies have demonstrated the potential use of stem cells for the repair and regeneration of injured tissues. However, tracking transplanted stem cell fate and function in vivo remains problematic. To address these issues, murine embryonic stem (ES) cells were stably transduced with self-inactivating lentiviral vectors carrying either a triple fusion (TF) or double fusion (DF) reporter gene construct. The TF consisted of monomeric red fluorescence protein (mrfp), firefly luciferase (Fluc), and herpes simplex virus truncated thymidine kinase (HSV-ttk) reporter genes. The DF consisted of enhanced green fluorescence protein (egfp) and Fluc reporter genes but lacked HSV-ttk. Stably transduced ES-TF or ES-DF cells were selected by fluorescence activated cell sorting based on either mrfp (TF) or egfp (DF) expression. Afterwards, cells were injected subcutaneously into the right (ES-TF cells) and left (ES-DF cells) shoulders of adult female nude mice. Cell survival was tracked noninvasively by bioluminescence and positron emission tomography imaging of Fluc and HSV-ttk reporter genes, respectively. Imaging signals progressively increased from day 2 to day 14, consistent with ES cell survival and proliferation in vivo. However, teratoma formation occurred in all nude mice after 5 weeks. Administration of ganciclovir (GCV), targeting the HSV-ttk gene, resulted in selective ablation of teratomas arising from the ES-TF cells but not ES-DF cells. These data demonstrate the novel use of multimodality imaging techniques to (1) monitor transplanted ES cell survival and proliferation in vivo and (2) assess the efficacy of suicide gene therapy as a backup safety measure against teratoma formation.


Are routine inferior vena cavograms necessary before Greenfield filter placement?
In August 1983 we began routinely studying the inferior vena cava (IVC) before placement of a Greenfield filter. We have performed 83 caval interruptions since that time, but six patients were excluded from this study because an IVC clip had been placed in three patients during other abdominal surgery, and the medical records of three others could not be retrieved. Of the remaining 77 patients, 65 (84%) had IVC venograms taken before placement of their filter. We personally reviewed 63 of these cavograms but had to accept the radiologist's reports for two studies that could not be retrieved. Ten (15%) cavograms showed abnormalities that significantly affected the placement of the filter. The most frequent abnormality was intracaval clot extending above the L3-4 interspace. Other important abnormalities were severe narrowing of the diaphragmatic IVC (two patients) and a tortuous IVC in a patient with severe scliosis. Seven (11%) additional cavograms showed unilateral iliac thrombus that would have influenced the surgical approach had a femoral approach been required. Formal preoperative cavography expedited filter placement and reduced operating time by obviating the need for intraoperative angiograms. Because 26% of the cavograms showed clinically important information, we recommend that routine IVC angiograms be taken before filter placement.


Plasmonic silicon solar cells: impact of material quality and geometry.
We study n-i-p amorphous silicon solar cells with light-scattering nanoparticles in the back reflector. In one configuration, the particles are fully embedded in the zinc oxide buffer layer; In a second configuration, the particles are placed between the buffer layer and the flat back electrode. We use stencil lithography to produce the same periodic arrangement of the particles and we use the same solar cell structure on top, thus establishing a fair comparison between a novel plasmonic concept and its more traditional counterpart. Both approaches show strong resonances around 700 nm in the external quantum efficiency the position and intensity of which vary strongly with the nanoparticle shape. Moreover, disagreement between simulations and our experimental results suggests that the dielectric data of bulk silver do not correctly represent the reality. A better fit is obtained by introducing a porous interfacial layer between the silver and zinc oxide. Without the interfacial layer, e.g. by improved processing of the nanoparticles, our simulations show that the nanoparticles concept could outperform traditional back reflectors.


Functional analysis of the Pseudomonas aeruginosa autoinducer PAI.
A series of structural analogs of the Pseudomonas aeruginosa autoinducer [PAI, N-3-oxo-dodecanoyl homoserine lactone] were obtained and tested for their ability to act as autoinducers in stimulating the expression of the gene for elastase (lasB) by measuring beta-galactosidase production from a lasB-lacZ gene fusion in the presence of the transcriptional activator LasR. The data suggest that the length of the acyl side chain of the autoinducer molecule is the most critical factor for activity. Replacement of the ring O by S in the homoserine lactone moiety can be tolerated. Tritium-labelled PAI ([3H]PAI) was synthesized and used to demonstrate the association of [3H]PAI with cells overexpressing LasR. The PAI analogs were also tested for their ability to compete with [3H]PAI for binding of LasR. Results from the competition assays suggest that once again the length of the acyl side chain appears to be crucial for antagonist activity. The presence of the 3-oxo moiety also plays a significant role in binding since analogs which lacked this moiety were much less effective in blocking binding of [3H]PAI. All analogs demonstrating competition with PAI in binding to LasR also exhibited the ability to activate lasB expression, suggesting that they are functional analogs of PAI.


Quality control procedures for genome-wide association studies.
Genome-wide association studies (GWAS) are being conducted at an unprecedented rate in population-based cohorts and have increased our understanding of the pathophysiology of complex disease. Regardless of context, the practical utility of this information will ultimately depend upon the quality of the original data. Quality control (QC) procedures for GWAS are computationally intensive, operationally challenging, and constantly evolving. Here we enumerate some of the challenges in QC of GWAS data and describe the approaches that the electronic MEdical Records and Genomics (eMERGE) network is using for quality assurance in GWAS data, thereby minimizing potential bias and error in GWAS results. We discuss common issues associated with QC of GWAS data, including data file formats, software packages for data manipulation and analysis, sex chromosome anomalies, sample identity, sample relatedness, population substructure, batch effects, and marker quality. We propose best practices and discuss areas of ongoing and future research.


Imagery about suicide in depression--"Flash-forwards"?
Suicide is a significant world health problem, with more deaths by suicide globally than by war. We need to better understand the cognitive processes underlying suicidal thinking for improved treatment development. Cognitive psychology indicates that mental imagery can be causal in determining future behavior, yet the occurrence of suicide-related imagery has not previously been investigated. Interviews with 15 depressed and formerly suicidal patients in remission found that all patients reported experiencing detailed mental imagery in addition to verbal thoughts when at their most despairing, for example images of making a future suicide attempt. A clinical measure of the severity of suicidal ideation was associated with both preoccupation with suicide-related imagery and perceived imagery realness. Echoing flashbacks in posttraumatic stress disorder, the current images appeared like "flash-forwards" to suicide. These results provide the first data to our knowledge on the existence of mental imagery in suicidality, opening a promising new avenue for research.


Application of microarray technology in primate behavioral neuroscience research.
Gene expression profiling of brain tissue samples applied to DNA microarrays promises to provide novel insights into the neurobiological bases of primate behavior. The strength of the microarray technology lies in the ability to simultaneously measure the expression levels of all genes in defined brain regions that are known to mediate behavior. The application of microarrays presents, however, various limitations and challenges for primate neuroscience research. Low RNA abundance, modest changes in gene expression, heterogeneous distribution of mRNA among cell subpopulations, and individual differences in behavior all mandate great care in the collection, processing, and analysis of brain tissue. A unique problem for nonhuman primate research is the limited availability of species-specific arrays. Arrays designed for humans are often used, but expression level differences are inevitably confounded by gene sequence differences in all cross-species array applications. Tools to deal with this problem are currently being developed. Here we review these methodological issues, and provide examples from our experiences using human arrays to examine brain tissue samples from squirrel monkeys. Until species-specific microarrays become more widely available, great caution must be taken in the assessment and interpretation of microarray data from nonhuman primates. Nevertheless, the application of human microarrays in nonhuman primate neuroscience research recovers useful information from thousands of genes, and represents an important new strategy for understanding the molecular complexity of behavior and mental health.


Combined androgen deprivation with radiotherapy for prostate cancer: does it make sense?
Currently, our understanding of the mechanism(s) of radiation-induced death of prostate cancer is limited. In-depth analysis of these processes would facilitate the design of more effective treatment strategies utilizing radiation therapy. An increasingly recognized form of radiation-induced death is postmitotic apoptosis. In this process, radiation damages the tumor cell s DNA. The cell then divides prior to completing DNA repair, an event that is lethal. In order to avoid this fate, the cancer cell may attempt to halt its cell-cycle machinery temporarily to repair its DNA prior to dividing. In the treatment of prostate cancer, radiation therapy currently is being evaluated in combination with androgen deprivation (AD). However, because AD can induce growth arrest, it may reduce the effectiveness of radiation through a reduction in postmitotic apoptosis. To study this effect, we examined the effect of AD on prostate cancer radiosensitivity as it is related to cell-cycle progression. Androgen-sensitive prostate cancer cells demonstrated increased resistance to radiation when deprived of androgenic stimuli. Thus, paradoxically, AD may reduce the radiosensitivity of prostate cancer by means of cell-cycle delay, which results in a reduction in postmitotic apoptosis.


TC2N, a novel oncogene, accelerates tumor progression by suppressing p53 signaling pathway in lung cancer.
The protein containing the C2 domain has been well documented for its essential roles in endocytosis, cellular metabolism and cancer. Tac2-N (TC2N) is a tandem C2 domain-containing protein, but its function, including its role in tumorigenesis, remains unknown. Here, we first identified TC2N as a novel oncogene in lung cancer. TC2N was preferentially upregulated in lung cancer tissues compared with adjacent normal lung tissues. High TC2N expression was significantly associated with poor outcome of lung cancer patients. Knockdown of TC2N markedly induces cell apoptosis and cell cycle arrest with repressing proliferation in vitro, and suppresses tumorigenicity in vivo, whereas overexpression of TC2N has the opposite effects both in vitro and in vivo. Using a combination of TCGA database and bioinformatics, we demonstrate that TC2N is involved in regulation of the p53 signaling pathway. Mechanistically, TC2N attenuates p53 signaling pathway through inhibiting Cdk5-induced phosphorylation of p53 via inducing Cdk5 degradation or disrupting the interaction between Cdk5 and p53. Moreover, the blockade of p53 attenuates the function of TC2N knockdown in the regulation of cell proliferation and apoptosis. In addition, downregulated TC2N is involved in the apoptosis of lung cancer cells induced by doxorubicin, leading to p53 pathway activation. Overall, these findings uncover a role for the p53 inactivator TC2N in regulating the proliferation and apoptosis of lung cancer cells. Our present study provides novel insights into the mechanism of tumorigenesis in lung cancer.


Exploitation of Mycobacterium tuberculosis reporter strains to probe the impact of vaccination at sites of infection.
Mycobacterium tuberculosis (Mtb) remains a major public health problem, with an effective vaccine continuing to prove elusive. Progress in vaccination strategies has been hampered by a lack of appreciation of the bacterium's response to dynamic changes in the host immune environment. Here, we utilize reporter Mtb strains that respond to specific host immune stresses such as hypoxia and nitric oxide (hspX'::GFP), and phagosomal maturation (rv2390c'::GFP), to investigate vaccine-induced alterations in the environmental niche during experimental murine infections. While vaccination undoubtedly decreased bacterial burden, we found that it also appeared to accelerate Mtb's adoption of a phenotype better equipped to survive in its host. We subsequently utilized a novel replication reporter strain of Mtb to demonstrate that, in addition to these alterations in host stress response, there is a decreased percentage of actively replicating Mtb in vaccinated hosts. This observation was supported by the differential sensitivity of recovered bacteria to the front-line drug isoniazid. Our study documents the natural history of the impact that vaccination has on Mtb's physiology and replication and highlights the value of reporter Mtb strains for probing heterogeneous Mtb populations in the context of a complex, whole animal model.


Alamethicin and related peptaibols--model ion channels.
Peptaibols are considered as models of those ion channels which consist of a bundle of transbilayer helices surrounding a central pore. X-Ray diffraction and NMR studies have yielded high resolution structures for several peptaibols. In conjunction with other spectroscopic investigations and molecular dynamics simulations, these studies suggest that peptaibols form proline-kinked alpha-helices, and that there may be "hinge-bending" movement of the helix in the region of the central proline residue. The amphipathicity of peptaibol helices is analyzed in relation to their channel-forming properties. Studies of the interactions of peptaibols with lipid bilayers suggest that they are helical when in a membrane-like environment, and that the helix orientation relative to the bilayer is sensitive to the peptaibol:lipid ratio, and to the degree of hydration of the bilayer. Electrical studies reveal that many peptaibols form multiple-conductance level channels in a voltage-dependent fashion. Analysis of conductance levels provides support for the "barrel stave" model of channel formation, whereby different conductance levels correspond to different numbers of monomers in a helix bundle. Alternative models for voltage-activation are discussed, and the roles of molecular dipoles and of hinge-bending in this process are considered. Two molecular models for an N = 6 bundle of alamethicin helices are presented and their electrostatic properties analyzed. The relevance of studies of peptaibols to channel and transport proteins in general is considered.


Conversion from depression to bipolar disorder in a cohort of young people in England, 1999-2011: A national record linkage study.
To estimate the conversion rate from unipolar depression (ICD10 codes F32-F33) to bipolar disorder (BP) (ICD10 codes F31) in an English national cohort. It was hypothesised that early-onset BP (age <18 years) is a more severe form of the disorder, with a more rapid, and higher rate of conversion from depression to BP. This record linkage study used English national Hospital Episode Statistics (HES) covering all NHS inpatient and day case admissions between 1999 and 2011. The overall rate of conversion from depression to BP for all ages was 5.65% (95% CI: 5.48-5.83) over a minimum 4-year follow-up period. The conversion rate from depression to BP increased in a linear manner with age from 10-14 years - 2.21% (95% C: 1.16-4.22) to 30-34 years - 7.06% (95% CI: 6.44-7.55) (F1,23=77.6, p=0.001, R(2)=0.77). The time to conversion was constant across the age range. The rate of conversion was higher in females (6.77%; 95% CI: 6.53-7.02) compared to males, (4.17%; 95% CI: 3.95-4.40) (χ(2)=194, p<0.0001), and in those with psychotic depression 8.12% (95% CI: 7.65-8.62) compared to non-psychotic depression 5.65% (95% CI: 5.48-5.83) (χ(2)=97.0, p<0.0001). The study was limited to hospital discharges and diagnoses were not standardised. Increasing conversion rate from depression to bipolar disorder with age, and constant time for conversion across the age range does not support the notion that early-onset BP is a more severe form of the disorder.


Prestimulus delta and theta determinants of ERP responses in the Go/NoGo task.
Ongoing low-frequency EEG activity has long been associated with ERP components and their cognitive processing interpretations, yet few studies have directly investigated the prestimulus low-frequency EEG-ERP relationships, particularly within the auditory domain. The present study assessed the delta (1-3 Hz) and theta (4-7 Hz) bands individually, and their prestimulus influence on five subsequent components (P1, N1, P2, N2, and P3) within an equiprobable auditory Go/NoGo paradigm. At the nine central sites, accepted trials were sorted according to their ascending vertex prestimulus spectral band amplitude, and ERPs were derived from the upper and lower sorted thirds. The within-subjects analyses included amplitudes and latencies for both Go and NoGo responses, and Go response speed. Only component amplitudes showed effects of high/low prestimulus EEG level. Delta globally modulated the five components - all amplitudes were more positive with high prestimulus delta, regardless of stimulus condition. Theta did not influence P1, but inversely modulated P2 and P3 regionally, and produced stimulus-specific effects in N1, N2, and P3. Low prestimulus theta produced greater NoGo N2 and Go P3, and reduced NoGo P3 responses, each of these suggesting appropriately enhanced cognitive processing. Taken together, these effect patterns differentially implicate prestimulus delta and theta band activity in the determination of ERP component amplitudes and the cognitive processing associated with them.


Estimating the cumulative incidence of COVID-19 in the United States using influenza surveillance, virologic testing, and mortality data: Four complementary approaches.
Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the prevalence of COVID-19 across the United States (US). Equipment shortages and varying testing capabilities have however hindered the usefulness of the official reported positive COVID-19 case counts. We introduce four complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 in each state in the US as well as Puerto Rico and the District of Columbia, using a combination of excess influenza-like illness reports, COVID-19 test statistics, COVID-19 mortality reports, and a spatially structured epidemic model. Instead of relying on the estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our four approaches emerges the consistent conclusion that on April 4, 2020, the estimated case count was 5 to 50 times higher than the official positive test counts across the different states. Nationally, our estimates of COVID-19 symptomatic cases as of April 4 have a likely range of 2.3 to 4.8 million, with possibly as many as 7.6 million cases, up to 25 times greater than the cumulative confirmed cases of about 311,000. Extending our methods to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 4.9 to 10.1 million, as opposed to 1.5 million positive test counts. The proposed combination of approaches may prove useful in assessing the burden of COVID-19 during resurgences in the US and other countries with comparable surveillance systems.


A new strategy for integrating abundant oxygen functional groups into carbon felt electrode for vanadium redox flow batteries.
The effects of surface treatment combining corona discharge and hydrogen peroxide (H2O2) on the electrochemical performance of carbon felt electrodes for vanadium redox flow batteries (VRFBs) have been thoroughly investigated. A high concentration of oxygen functional groups has been successfully introduced onto the surface of the carbon felt electrodes by a specially designed surface treatment, which is mainly responsible for improving the energy efficiency of VRFBs. In addition, the wettability of the carbon felt electrodes also can be significantly improved. The energy efficiency of the VRFB cell employing the surface modified carbon felt electrodes is improved by 7% at high current density (148 mA cm(-2)). Such improvement is attributed to the faster charge transfer and better wettability allowed by surface-active oxygen functional groups. Moreover, this method is much more competitive than other surface treatments in terms of processing time, production costs, and electrochemical performance.


Sit-to-stand-and-walk from 120% Knee Height: A Novel Approach to Assess Dynamic Postural Control Independent of Lead-limb.
Individuals with sensorimotor pathology e.g., stroke have difficulty executing the common task of rising from sitting and initiating gait (sit-to-walk: STW). Thus, in clinical rehabilitation separation of sit-to-stand and gait initiation - termed sit-to-stand-and-walk (STSW) - is usual. However, a standardized STSW protocol with a clearly defined analytical approach suitable for pathological assessment has yet to be defined. Hence, a goal-orientated protocol is defined that is suitable for healthy and compromised individuals by requiring the rising phase to be initiated from 120% knee height with a wide base of support independent of lead limb. Optical capture of three-dimensional (3D) segmental movement trajectories, and force platforms to yield two-dimensional (2D) center-of-pressure (COP) trajectories permit tracking of the horizontal distance between COP and whole-body-center-of-mass (BCOM), the decrease of which increases positional stability but is proposed to represent poor dynamic postural control. BCOM-COP distance is expressed with and without normalization to subjects' leg length. Whilst COP-BCOM distances vary through STSW, normalized data at the key movement events of seat-off and initial toe-off (TO1) during steps 1 and 2 have low intra and inter subject variability in 5 repeated trials performed by 10 young healthy individuals. Thus, comparing COP-BCOM distance at key events during performance of an STSW paradigm between patients with upper motor neuron injury, or other compromised patient groups, and normative data in young healthy individuals is a novel methodology for evaluation of dynamic postural stability.


The risk of fracture in patients with multiple sclerosis: the UK general practice research database.
Patients with multiple sclerosis (MS) may be at an increased risk of fracture owing to a greater risk of falling and decreased bone mineral density when compared with the general population. This study was designed to estimate the relative and absolute risk of fracture in patients with MS. We conducted a population-based cohort study using data from the UK General Practice Research Database linked to the National Hospital Registry (1997-2008). Incident MS patients (n = 5565) were matched 1:6 by year of birth, sex, and practice with patients without MS (controls). Cox proportional-hazards models were used to derive adjusted hazard ratios (HRs) for fracture associated with MS. Time-dependent adjustments were made for age, comorbidity, and drug use. Absolute 5- and 10-year risks of fracture were estimated for MS patients as a function of age. Compared with controls, MS patients had an almost threefold increased risk of hip fracture [HR = 2.79, 95% confidence interval (CI) 1.83-4.26] and a risk of osteoporotic fracture that was increased 1.4-fold (HR = 1.35, 95% CI 1.13-1.62). Risk was greater in patients who had been prescribed oral/intravenous glucocorticoids (GCs; HR = 1.85, 95% CI 1.14-2.98) or antidepressants (HR = 1.79, 95% CI 1.37-2.35) in the previous 6 months. Absolute fracture risks were low in younger MS patients but became substantial when patients were older than 60 years of age. It is concluded that MS is associated with an increased risk of fracture. Fracture risk assessment may be indicated in patients with MS, especially those prescribed GCs or antidepressants.


The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation.
In Drosophila, the MSL complex is required for the dosage compensation of X-linked genes in males and contains a histone acetyltransferase, MOF. A point mutation in the MOF acetyl-CoA-binding site results in male-specific lethality. Yeast Esa1p, a MOF homolog, is essential for cell cycle progression and is the catalytic subunit of the NuA4 acetyltransferase complex. Here we report that NuA4 purified from yeast with a point mutation in the acetyl-CoA-binding domain of Esa1p exhibits a strong decrease in histone acetyltransferase activity, yet has no effect on growth. We demonstrate that Eaf3p (Esa1p-associated factor-3 protein), a yeast protein homologous to the Drosophila dosage compensation protein MSL3, is also a stable component of the NuA4 complex. Unlike other subunits of the complex, it is not essential, and the deletion mutant has no growth phenotype. NuA4 purified from the mutant strain has a decreased apparent molecular mass, but retains wild-type levels of histone H4 acetyltransferase activity. The EAF3 deletion and the ESA1 mutation lead to a decrease in PHO5 gene expression; the EAF3 deletion also significantly reduces HIS4 and TRP4 expressions. These results, together with those previously obtained with both the MSL and NuA4 complexes, underscore the importance of targeted histone H4 acetylation for the gene-specific activation of transcription.


Reverse osmosis desalination: water sources, technology, and today's challenges.
Reverse osmosis membrane technology has developed over the past 40 years to a 44% share in world desalting production capacity, and an 80% share in the total number of desalination plants installed worldwide. The use of membrane desalination has increased as materials have improved and costs have decreased. Today, reverse osmosis membranes are the leading technology for new desalination installations, and they are applied to a variety of salt water resources using tailored pretreatment and membrane system design. Two distinct branches of reverse osmosis desalination have emerged: seawater reverse osmosis and brackish water reverse osmosis. Differences between the two water sources, including foulants, salinity, waste brine (concentrate) disposal options, and plant location, have created significant differences in process development, implementation, and key technical problems. Pretreatment options are similar for both types of reverse osmosis and depend on the specific components of the water source. Both brackish water and seawater reverse osmosis (RO) will continue to be used worldwide; new technology in energy recovery and renewable energy, as well as innovative plant design, will allow greater use of desalination for inland and rural communities, while providing more affordable water for large coastal cities. A wide variety of research and general information on RO desalination is available; however, a direct comparison of seawater and brackish water RO systems is necessary to highlight similarities and differences in process development. This article brings to light key parameters of an RO process and process modifications due to feed water characteristics.


Genetic diversity of mitochondrial control region (D-Loop) polymorphisms in Coilia ectenes taihuensis inhabiting Taihu Lake, China.
Coilia ectenes is a commercially important fishery species in China. C. ectenes taihuensis is an endemic and dominant species found in Taihu Lake of China. When compared with C. ectenes, C. ectenes taihuensis lacks anadromous behavior, and can independently grow and reproduce in Taihu Lake. In this study, the mitochondrial DNA control region (D-loop) sequences were employed to investigate the genetic diversity and population structure of C. ectenes taihuensis. Sixty-eight individuals collected from 4 localities in Taihu Lake were examined. Results indicated that in the 887-bp D-loop region, seventy-seven (8.68%) sites were variant, contributing to 53 distinct haplotypes. Although the population haplotype diversity (Hd = 0.971 to 1.000) was generally high, the nucleotide diversity (π = 0.616 to 0.731%) was relatively low among the 4 populations. Additionally, the genetic distances ranged from 0.62 to 0.74% within the populations and from 0.67 to 0.74% between the populations. The neighbor-joining tree indicated that a distinct distribution of phylogenetic structure existed among haplotypes. Analysis of molecular variance and FST statistics suggested that a divergence existed among populations in 4 localities, indicating that gene communication might have occurred among those populations. Furthermore, neutral tests and analysis of mismatch distribution reflected that C. ectenes taihuensis might have undergone a population expansion during the evolution process. Our study showed the population genetic diversity and structure of C. ectenes taihuensis. Results from this study might be helpful in the development and protection of fishery resource within the localities in Taihu Lake in future.


Emotion, decision making, and the amygdala.
Emotion plays a critical role in many contemporary accounts of decision making, but exactly what underlies its influence and how this is mediated in the brain remain far from clear. Here, we review behavioral studies that suggest that Pavlovian processes can exert an important influence over choice and may account for many effects that have traditionally been attributed to emotion. We illustrate how recent experiments cast light on the underlying structure of Pavlovian control and argue that generally this influence makes good computational sense. Corresponding neuroscientific data from both animals and humans implicate a central role for the amygdala through interactions with other brain areas. This yields a neurobiological account of emotion in which it may operate, often covertly, to optimize rather than corrupt economic choice.


The Landscape of Circular RNA in Cancer.
Circular RNAs (circRNAs) are an intriguing class of RNA due to their covalently closed structure, high stability, and implicated roles in gene regulation. Here, we used an exome capture RNA sequencing protocol to detect and characterize circRNAs across >2,000 cancer samples. When compared against Ribo-Zero and RNase R, capture sequencing significantly enhanced the enrichment of circRNAs and preserved accurate circular-to-linear ratios. Using capture sequencing, we built the most comprehensive catalog of circRNA species to date: MiOncoCirc, the first database to be composed primarily of circRNAs directly detected in tumor tissues. Using MiOncoCirc, we identified candidate circRNAs to serve as biomarkers for prostate cancer and were able to detect circRNAs in urine. We further detected a novel class of circular transcripts, termed read-through circRNAs, that involved exons originating from different genes. MiOncoCirc will serve as a valuable resource for the development of circRNAs as diagnostic or therapeutic targets across cancer types.


Surface roughness after excimer laser ablation using a PMMA model: profilometry and effects on vision.
To show that the limited quality of surfaces produced by one model of excimer laser systems can degrade visual performance with a polymethylmethacrylate (PMMA) model. A range of lenses of different powers was ablated in PMMA sheets using five DOS-based Nidek EC-5000 laser systems (Nidek Technologies, Gamagori, Japan) from different clinics. Surface quality was objectively assessed using profilometry. Contrast sensitivity and visual acuity were measured through the lenses when their powers were neutralized with suitable spectacle trial lenses. Average surface roughness was found to increase with lens power, roughness values being higher for negative lenses than for positive lenses. Losses in visual contrast sensitivity and acuity measured in two subjects were found to follow a similar pattern. Findings are similar to those previously published with other excimer laser systems. Levels of surface roughness produced by some laser systems may be sufficient to degrade visual performance under some circumstances.


A probabilistic palimpsest model of visual short-term memory.
Working memory plays a key role in cognition, and yet its mechanisms remain much debated. Human performance on memory tasks is severely limited; however, the two major classes of theory explaining the limits leave open questions about key issues such as how multiple simultaneously-represented items can be distinguished. We propose a palimpsest model, with the occurrent activity of a single population of neurons coding for several multi-featured items. Using a probabilistic approach to storage and recall, we show how this model can account for many qualitative aspects of existing experimental data. In our account, the underlying nature of a memory item depends entirely on the characteristics of the population representation, and we provide analytical and numerical insights into critical issues such as multiplicity and binding. We consider representations in which information about individual feature values is partially separate from the information about binding that creates single items out of multiple features. An appropriate balance between these two types of information is required to capture fully the different types of error seen in human experimental data. Our model provides the first principled account of misbinding errors. We also suggest a specific set of stimuli designed to elucidate the representations that subjects actually employ.


Analysis of Genetic Variation across the Encapsidated Genome of Microplitis demolitor Bracovirus in Parasitoid Wasps.
Insect parasitoids must complete part of their life cycle within or on another insect, ultimately resulting in the death of the host insect. One group of parasitoid wasps, the 'microgastroid complex' (Hymenoptera: Braconidae), engage in an association with beneficial symbiotic viruses that are essential for successful parasitism of hosts. These viruses, known as Bracoviruses, persist in an integrated form in the wasp genome, and activate to replicate in wasp ovaries during development to ultimately be delivered into host insects during parasitism. The lethal nature of host-parasitoid interactions, combined with the involvement of viruses in mediating these interactions, has led to the hypothesis that Bracoviruses are engaged in an arms race with hosts, resulting in recurrent adaptation in viral (and host) genes. Deep sequencing was employed to characterize sequence variation across the encapsidated Bracovirus genome within laboratory and field populations of the parasitoid wasp species Microplitis demolitor. Contrary to expectations, there was a paucity of evidence for positive directional selection among virulence genes, which generally exhibited signatures of purifying selection. These data suggest that the dynamics of host-parasite interactions may not result in recurrent rounds of adaptation, and that adaptation may be more variable in time than previously expected.


Sulphurous-arsenical-ferruginous (thermal) water inhalations reduce nasal respiratory resistance and improve mucociliary clearance in patients with chronic sinonasal disease: preliminary outcomes.
In order to confirm these preliminary results, a prospective double-blind study has been instituted in Padova University ENT Section to compare the efficacy of sulphurous-arsenical-ferruginous thermal water nasal irrigations vs isotonic sodium chloride solution nasal irrigations after functional endoscopic sinus surgery for chronic sinusitis. Despite their widespread use, much uncertainty exists about the indications and therapeutic mechanisms of nasal thermal water inhalations in the treatment of sinonasal chronic disease. The aim of the present study was to evaluate the effects of sulphurous-arsenical-ferruginous thermal water inhalations on nasal respiratory flow, mucociliary transport, nasal cytology, and chemo-physics of nasal mucus in a group of consecutive patients with chronic sinonasal disease. Thirty-seven patients with chronic sinonasal disease underwent a 12-day course of sulphurous-arsenical-ferruginous thermal water warm vapour inhalations (38 degrees C) followed by nasal aerosol of the same thermal water (7 microns micelle). This preliminary study showed that a course of sulphurous-arsenical-ferruginous thermal water inhalations determined a significant improvement in nasal flow and reduction of nasal resistance; a statistically significant reduction of mean mucociliary transport time, from pathologic to physiologic values, has also been shown. Statistical analysis of our data confirmed that the presence of nasal bacteria was significantly reduced by thermal water inhalations.


Conversation versus narration in pre-school children with language impairment.
The study focuses on two elicitation methods for language sampling in children with language impairment: conversation and narration. It has been noted in other studies on different clinical groups that language elicited in different speaking contexts varies in aspects such as MLU, fluency and syntactic complexity. The purpose of this study was to compare genre effects on different aspects of language production in a group of pre-school children with language impairment. The results show that there are differences in language production during conversation compared with narration. Intelligibility and fluency were found to be higher in conversation than in narration, whereas MLU in words was higher in narration. The narrative task elicited more phrasal expansions and grammatical morphemes per utterance than the conversation. However, the children used more complex verb forms in conversation than in narration. The results are discussed in relation to recent research.


Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes.
The appearance of phosphatidylserine (PS) on the cell surface during apoptosis in thymocytes and cytotoxic T lymphocyte cell lines provokes PS-dependent recognition by activated macrophages. Flow cytometric analysis of transbilayer lipid movements in T lymphocytes undergoing apoptosis reveals that downregulation of the adenosine triphosphate-dependent amino-phospholipid translocase and activation of a nonspecific lipid scramblase are responsible for PS reaching the surface from its intracellular location. Both mechanisms are expressed at the same time, and precede DNA degradation, zeiosis, and cell lysis in the apoptotic pathway.


Assessing the Relationship Between Religious Involvement and Health Behaviors.
A growing body of research suggests that people who are more deeply involved in religion may be more likely to adopt beneficial health behaviors. However, religion is a complex phenomenon, and as a result, religion may affect health behaviors in a number of ways. The purpose of the current study was to see whether a sacred view of the body (i.e., belief that the body is the temple of God) is associated with better health behavior. It was proposed that the relationship between a sacred body view and health behavior will emerge only among study participants who have a stronger sense of religiously oriented control (i.e., stronger God-mediated control beliefs). Five positive health behaviors were evaluated: more frequent strenuous exercise, more frequent moderate exercise, more frequent consumption of fruits and vegetables, higher quality sleep, and the adoption of healthy lifestyles. Data from a recent nationwide sample reveal that a sacred body view is associated with each health behavior, but only among study participants who have a strong religiously oriented sense of control.


Epigenetic regulation of HYAL-1 hyaluronidase expression. identification of HYAL-1 promoter.
HYAL-1 (hyaluronoglucosaminidase-1) belongs to the hyaluronidase family of enzymes that degrade hyaluronic acid. HYAL-1 is a marker for cancer diagnosis and a molecular determinant of tumor growth, invasion, and angiogenesis. The regulation of HYAL-1 expression is unknown. Real time reverse transcription-PCR using 11 bladder and prostate cancer cells and 69 bladder tissues showed that HYAL-1 mRNA levels are elevated 10-30-fold in cells/tissues that express high hyaluronidase activity. Although multiple transcription start sites (TSS) for HYAL-1 mRNA were detected in various tissues, the major TSS in many tissues, including bladder and prostate, was at nucleotide 27274 in the cosmid clone LUCA13 (AC002455). By analyzing the 1532 base sequence 5' to this TSS, using cloning and luciferase reporter assays, we identified a TACAAA sequence at position -31 and the minimal promoter region between nucleotides -93 and -38. Mutational analysis identified that nucleotides -73 to -50 (which include overlapping binding consensus sites for SP1, Egr-1, and AP-2), bases C(-71) and C(-59), and an NFkappaB-binding site (at position -15) are necessary for promoter activity. The chromatin immunoprecipitation assay identified that Egr-1, AP-2, and NFkappaB bind to the promoter in HYAL-1-expressing cells, whereas SP1 binds to the promoter in non-HYAL-1-expressing cells. 5-Aza-2'-deoxycytidine treatment, bisulfite DNA sequencing, and methylation-specific PCR revealed that HYAL-1 expression is regulated by methylation at C(-71) and C(-59); both Cs are part of the SP1/Egr-1-binding sites. Thus, HYAL-1 expression is epigenetically regulated by the binding of different transcription factors to the methylated and unmethylated HYAL-1 promoter.


Dopamine toxicity in neuroblastoma cells: role of glutathione depletion by L-BSO and apoptosis.
Dopamine (DA), while an essential neurotransmitter, is also a known neurotoxin that potentially plays an etiologic role in several neurodegenerative diseases. DA metabolism and oxidation readily produce reactive oxygen species (ROS) and DA can also be oxidized to a reactive quinone via spontaneous, enzyme-catalyzed or metal-enhanced reactions. A number of these reactions are cytotoxic, yet the precise mechanisms by which DA leads to cell death remain unknown. In this study, the neuroblastoma cell line, SK-N-SH, was utilized to examine DA toxicity under varying oxidant states. Cells pretreated with the glutathione (GSH)-depleting compound, L-buthionine sulfoximine (L-BSO), exhibited enhanced sensitivity to DA compared to controls (non-GSH-depleted cells). Furthermore, in cells pretreated with L-BSO, the addition of ascorbate (250 microM) afforded significant protection against DA-induced toxicity, while pyruvate (500 microM) had no protective effect. To further characterize the possibility that DA is associated with oxidative stress, additional studies were carried out with manganese (30 microM) as a pro-oxidant. Manganese and DA (200 microM), although not cytotoxic when individually administered to SK-N-SH cells, had a synergistic action on cytotoxicity. Finally, morphological and molecular markers of programmed cell death (apoptosis) were observed in cells treated with DA and L-BSO. These markers included membrane blebbing and internucleosomal DNA fragmentation. These results suggest that DA toxicity is tightly linked to intracellular oxidant/antioxidant levels, and that environmental factors, such as excessive Mn exposure, may modulate cellular sensitivity to DA.


The Men's Safer Sex Trial: A feasibility randomised controlled trial of an interactive digital intervention to increase condom use in men.
We aimed to determine the feasibility of an online randomised controlled trial (RCT) of the Men's Safer Sex website, measuring condom use and sexually transmitted infection (STI). For this study 159 men aged ≥16 with female sexual partners and recent condomless sex or suspected STI were recruited from three UK sexual health clinics. Participants were randomised to the intervention website plus usual clinic care (n = 84), or usual clinic care only (n = 75). Online outcome data were solicited at 3, 6, and 12 months. Men were enrolled via tablet computers in clinic waiting rooms. Software errors and clinic Wi-Fi access presented significant challenges, and online questionnaire response rates were poor (36% at 3 months with a £10 voucher; 50% at 12 months with £30). Clinical records (for STI diagnoses) were located for 94% of participants. Some 37% of the intervention group did not see the intervention website (n = 31/84), and (as expected) there was no detectable difference in condomless sex with female partners (IRR = 1.01, 95% CI 0.52 to 1.96). New acute STI diagnoses were recorded for 8.8% (7/80) of the intervention group, and 13.0% (9/69) of the control group over 12 months (IRR = 0.75, 95% CI 0.29 to 1.90). It is likely to be feasible to conduct a future large-scale RCT to assess the impact of an online intervention using clinic STI diagnoses as a primary outcome. However, practical and technical challenges need to be addressed before the potential of digital media interventions can be realised in sexual health settings.Trial registration number: ISRCTN18649610.


Feasibility of a stem cell therapy for intervertebral disc degeneration.
Different strategies to supplement/replenish the disc cell population have been proposed. Recently, adult stem cells have shown promise as a cell source for a variety of tissue engineering and cell therapy applications. A stem cell can renew itself through cell division and can be induced to develop into many different specialized cell types. Moreover, stem cells have shown ability to migrate and engraft within various tissues, as well as to exert stimulatory effects on other cell types through various mechanisms (eg, paracrine effects, cell-cell interactions). These characteristics make stem cells worthy of investigation as a source of cells for intervertebral disc (IVD) tissue engineering and cell therapy. To determine feasibility of a stem cell therapy of IVD degeneration. In vitro studies of adult human cells to examine interactions between nucleus pulposus cells (NPCs) and mesenchymal stem cells (MSCs) at different ratios in 3-D pellet culture. In vivo studies of healthy adult rabbit discs injected with allogenic adult rabbit MSCs to examine stem cell survival and engraftment in living disc tissue. In vitro study: Human NPCs were cocultured with human MSCs in different ratios (75:25, 50:50, 25:75) for 2 weeks in pellet culture, for comparison with pure NPC (100:0) and pure MSC (0:100) pellet cultures. Proteoglycan synthesis rate and glycosaminoglycan (GAG) content were measured by radioactive sulfate incorporation and dimethylmethylene blue assay, respectively. In vivo study: MSCs were isolated from the bone marrow of a New Zealand White (NZW) rabbit, retrovirally transduced with the lacZ marker gene, and injected into the nucleus pulposi of the L2-3, L3-4, and L4-5 lumbar discs of 12 other NZW rabbits. Three rabbits each were sacrificed at 3, 6, 12, or 24 weeks after cell implantation, and X-Gal staining was done to assess survival and localization of MSCs in the disc tissues. In vitro study: the 75:25 and 50:50 NPC:MSC cocultures yielded the greatest increases in extracellular matrix (ECM) production. In vivo study: MSCs were detected in histological sections of rabbit discs up to 24 weeks after allogenic stem cell implantation, without evidence of systemic illness in the recipient rabbits. The 24-week results in particular suggested the possibility of stem cell migration and engraftment into the inner annulus fibrosus. These encouraging results support feasibility of a stem cell therapy approach toward supplementation/replenishment of IVD cells and synthesis/maintenance of a more functional ECM in a degenerated disc. Moreover, the in vivo results demonstrate that transplanted MSCs survive and successfully engraft into the IVD tissue, and are effective vehicles for exogenous gene delivery to the IVD--thus there appear to be multiple mechanisms whereby stem cells might able to confer therapeutic effects in a stem cell therapy of IVD degeneration.


Targeting PI3K-p110α Suppresses Influenza Virus Infection in Chronic Obstructive Pulmonary Disease.
Chronic obstructive pulmonary disease (COPD) and influenza virus infections are major global health issues. Patients with COPD are more susceptible to infection, which exacerbates their condition and increases morbidity and mortality. The mechanisms of increased susceptibility remain poorly understood, and current preventions and treatments have substantial limitations. To characterize the mechanisms of increased susceptibility to influenza virus infection in COPD and the potential for therapeutic targeting. We used a combination of primary bronchial epithelial cells (pBECs) from COPD and healthy control subjects, a mouse model of cigarette smoke-induced experimental COPD, and influenza infection. The role of the phosphoinositide-3-kinase (PI3K) pathway was characterized using molecular methods, and its potential for targeting assessed using inhibitors. COPD pBECs were susceptible to increased viral entry and replication. Infected mice with experimental COPD also had more severe infection (increased viral titer and pulmonary inflammation, and compromised lung function). These processes were associated with impaired antiviral immunity, reduced retinoic acid-inducible gene-I, and IFN/cytokine and chemokine responses. Increased PI3K-p110α levels and activity in COPD pBECs and/or mice were responsible for increased infection and reduced antiviral responses. Global PI3K, specific therapeutic p110α inhibitors, or exogenous IFN-β restored protective antiviral responses, suppressed infection, and improved lung function. The increased susceptibility of individuals with COPD to influenza likely results from impaired antiviral responses, which are mediated by increased PI3K-p110α activity. This pathway may be targeted therapeutically in COPD, or in healthy individuals, during seasonal or pandemic outbreaks to prevent and/or treat influenza.


Patterns of prescription of antidepressants and antipsychotics across and within pregnancies in a population-based UK cohort.
Although antidepressant and antipsychotic utilization by gestational trimester has been described, longitudinal prescription patterns within pregnancies have received less attention. All mothers in the Clinical Practice Research Datalink's Mother Baby Link enrolled from 6 months before pregnancy to 3 months after delivery, with delivery date between 01/1989 and 12/2010 were included (n = 421,645). Drug use prevalence was calculated as the number of women with prescriptions for antidepressants or antipsychotics in capsules/tablets in the 3 months before pregnancy (T0), the first (T1), second (T2), or third (T3) pregnancy trimesters, or the 3 months after delivery (T4). In each pregnancy, prescriptions in T0 and T3 were compared to identify treatment discontinuation, simplification (some drugs discontinued or dose lowered), no treatment change, intensification (drugs added to prior treatment or dose increased), and start. Antidepressant use in T0 through T4 was 4.69, 2.81, 1.31, 1.34, and 5.46 %, respectively. Of 19,774 T0 antidepressant users, 79.57 % discontinued, 5.13 % simplified, 9.06 % did not change, and 2.19 % intensified treatment. 0.40 % of non-users in T0 started antidepressants by T3. Antipsychotic use in T0 through T4 was 0.57, 1.34, 0.54, 0.28 and 0.38 %. Excluding prochlorperazine, it was 0.15, 0.13, 0.08, 0.07 and 0.15 %, respectively; of 639 T0 users, 72.30 % discontinued, 7.51 % simplified, 11.11 % did not change, and 4.07 % intensified treatment. 0.03 % of non-users in T0 started antipsychotics by T3. Cross-sectional and longitudinal analyses identified a post-conception decrease in antidepressant and antipsychotic prescribing. Longitudinal treatment assessment additionally captured several treatment patterns among those who do not discontinue treatment that usually stay unrecognized.


Biological activities of synthetic analogs of halocidin, an antimicrobial peptide from the tunicate Halocynthia aurantium.
Halocidin is a heterodimer antimicrobial peptide previously isolated from the tunicate Halocynthia aurantium. Based on the larger monomer (18Hc) of halocidin, nine halocidin congeners, including a series of 6 peptides truncated successively from the carboxyl-terminal end of 18Hc and 3 analogs (18HcKK, K19Hc, and K19HcKK), which have lysine residues in place of two internal histidines or have a lysine added to the amino terminus of the 18Hc molecule, were prepared. Each peptide was also converted into a homodimeric version. The antimicrobial activities of halocidin congeners truncated from the C terminus were dramatically decreased, suggesting that the full length of 18Hc is required for maintaining its maximum antimicrobial activity. Dimer forms of halocidin congeners exhibited stronger antimicrobial activities than the monomer of the corresponding peptide. Four dimer peptides (di-18Hc, di-18HcKK, di-K19Hc, and di-K19HcKK) were analyzed for antimicrobial activities against 10 clinically isolated antibiotic-resistant bacteria in elevated concentrations of NaCl or MgCl(2). Of the peptides studied here, di-K19Hc retained invariably strong activity against all bacteria in diverse conditions and also showed much reduced hemolytic activity against human erythrocytes.


The effect of manganese on the oxidation of chemicals by lignin peroxidase.
It has recently been discovered that lignin peroxidase isozyme H2 (LiPH2) has the ability to oxidize Mn2+ (Khindaria et al., 1995). Furthermore, at pH 4.5, the physiological pH of Phanerochaete chrysosporium, LiPH2 oxidizes Mn2+ at a much faster rate (25 times) than veratryl alcohol (VA). The ability of Mn2+ to act as a redox mediator for indirect oxidations catalyzed by LiPH2 was therefore investigated. In the presence of physiologically relevant levels of oxalate and Mn2+, the rate of LiPH2-catalyzed oxidation of all substrates studied was dramatically increased. Up to 10-fold stimulations were observed compared to the rates of oxidation of substrate in either the presence or absence of VA. We propose that the stimulation is due to the ability of LiPH2 to oxidize Mn2+, producing the strong oxidant Mn3+, at a high rate. The rates of oxidation of the substrates showed a hyperbolic dependence on Mn2+ in the presence of oxalate, a chelator which was required for maximal activity. The oxalate dependence of the oxidation rates correlated well with the concentration of the 1:1 complex of Mn(2+)-oxalate. The relative concentrations of the substrates and H2O2 and the rate constants for their reactions with Mn3+ determined which chemical was oxidized by the enzymatically produced Mn3+. The importance of the ability of Mn(2+)-oxalate to stimulate the oxidation of chemicals by LiPH2 is discussed.


Imaging lung perfusion.
From the first measurements of the distribution of pulmonary blood flow using radioactive tracers by West and colleagues (J Clin Invest 40: 1-12, 1961) allowing gravitational differences in pulmonary blood flow to be described, the imaging of pulmonary blood flow has made considerable progress. The researcher employing modern imaging techniques now has the choice of several techniques, including magnetic resonance imaging (MRI), computerized tomography (CT), positron emission tomography (PET), and single photon emission computed tomography (SPECT). These techniques differ in several important ways: the resolution of the measurement, the type of contrast or tag used to image flow, and the amount of ionizing radiation associated with each measurement. In addition, the techniques vary in what is actually measured, whether it is capillary perfusion such as with PET and SPECT, or larger vessel information in addition to capillary perfusion such as with MRI and CT. Combined, these issues affect quantification and interpretation of data as well as the type of experiments possible using different techniques. The goal of this review is to give an overview of the techniques most commonly in use for physiological experiments along with the issues unique to each technique.


Angle-resolved reflectance of obliquely aligned silver nanorods.
Arrays of silver nanorods (AgNRs) formed by oblique-angle deposition (OAD) are strongly anisotropic, with either metallic or dielectric characteristics depending on the polarization of incident light, and may be used to enhance Raman scattering and surface plasmon polaritons. This work investigates the polarization-dependent reflectance of inclined AgNR arrays at the wavelengths of 635 and 977 nm. The specular reflectance at various incidence angles and the bidirectional reflectance distribution function were measured with a laser scatterometer, while the directional-hemispherical reflectance was measured with an integrating sphere. The AgNR layer is modeled as an effectively homogenous, optically uniaxial material using the effective medium theory to elucidate the dielectric or metallic response for differently polarized incidence. The thin-film optics formulation is modified considering optical anisotropy and surface scattering. This study helps gain a better understanding of optical properties of nanostructured materials.


Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer's disease.
Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is often sought from neuroimaging, including single-photon emission computed tomography (SPECT). Most previous SPECT studies lack pathological validation. To examine the accuracy of SPECT in differentiating FTD from AD in patients with subsequent pathological confirmation. Technetium-99-labelled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD were examined. These images were visually rated by an experienced blinded nuclear medicine consultant and compared with those of 31 patients with AD, also with pathological validation. A reduction in frontal cerebral blood flow (CBF) was more common in FTD and was of diagnostic value (sensitivity 0.8, specificity 0.65 and likelihood ratio (LR) 2.25; 95% CI 1.35 to 3.77). A pattern of bilateral frontal CBF reduction without the presence of associated bilateral parietal CBF change is diagnostically more accurate (sensitivity 0.80, specificity 0.81 and +LR 4.13, 95% CI 1.96 to 8.71). Diagnostic categorisation (FTD or AD) on the basis of SPECT alone was less accurate than clinical diagnosis (based on neurology and detailed neuropsychological evaluation). One patient with FTD was initially clinically misdiagnosed as AD, owing to the lack of availability of full neuropsychological assessment. However, SPECT correctly diagnosed this patient, providing a diagnostic gain of 4%. Technetium-99-labelled hexamethyl propylene amine oxime SPECT CBF patterns provide valuable information in the diagnosis of FTD and AD. These data can be better used as an adjunct to clinical diagnosis if pathology is to be correctly predicted in life.


The influence of environmental factors in chronic venous insufficiency.
The present article focuses on the prevalence and risk factors for varicose veins and the severe stage of chronic venous insufficiency (CVI). The evaluation was made by reviewing the results of specific well-designed studies performed on the general population (case-control studies, cross-sectional studies, and large case series). Data from the literature were compared with the results of a recent multicenter cross-sectional study in Poland, in which 40,095 individuals from 803 registers of primary care physicians were clinically examined and assigned a clinical CEAP class. Analysis of the associations between varicose veins or severe CVI prevalence and factors that are usually considered as representing a risk for the development of CVI was performed. In Poland, a prevalence of varicose veins and severe CVI (skin changes, leg ulcer) similar to that observed in the other developed countries was reported. It was more common in women, but female sex was not found to be a strong risk factor. Among the risk factors most closely associated with CVI were age, family history of varicose veins, and constipation, whatever the sex. This is in keeping with findings from recent epidemiologic studies. Obesity and lack of physical activity were strongly associated with CVI in women, more so than in men. The number of pregnancies (more than 2 pregnancies) significantly distinguished between women with and without CVI. Regarding these latter risk factors, the Polish results do not contradict the commonly held beliefs that are found in the literature. A modest association was found with female sex, previous injury in legs (DVT), and remaining in the standing position for a long time, although these parameters are usually among those mostly agreed as being risk factors. The role of the prolonged sitting position was not established. The Polish epidemiologic survey provided updated figures on the prevalence of and risk factors for varicose veins and severe CVI, using clear and globally accepted clinical definitions for the venous disease based on the CEAP classification.


Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium falciparum malaria.
The relationship between malaria-related outcomes and cytokine production in whole blood cultures associated with cellular immune responses and immunity to Plasmodium falciparum malaria was examined in a study in southern Ghana. Production of malaria-specific interferon (IFN)-gamma was associated with reduced risk of fever and clinical malaria. Protective IFN-gamma responses were induced by live schizonts but not by dead parasites. Production of malaria-specific tumor necrosis factor (TNF)-alpha was associated with reduced risk of fever during follow-up. Baseline levels of TNF-alpha and phytohemagglutinin (PHA)-induced interleukin (IL)-10 were positively associated with hemoglobin concentration. IL-12 production was associated with reduced risk of parasitemia. PHA-induced transforming growth factor-beta production was associated with reduced risk of fever during follow-up. High ratios of proinflammatory to anti-inflammatory cytokines were associated with increased risk of fever and higher hemoglobin concentrations. Thus, absolute levels and ratios of proinflammatory and anti-inflammatory cytokines influence susceptibility to infection, clinical disease, and anemia. These data contradict data from cross-sectional clinical studies and indicate a need for detailed analysis of the relationship between cellular immunity to malaria and resistance to disease.


The impact of obesity on the rise in esophageal adenocarcinoma incidence: estimates from a disease simulation model.
The United States has experienced an alarming and unexplained increase in the incidence of esophageal adenocarcinoma (EAC) since the 1970s. A concurrent increase in obesity has led some to suggest a relationship between the two trends. We explore the extent of this relationship. Using a previously validated disease simulation model of white males in the United States, we estimated EAC incidence 1973 to 2005 given constant obesity prevalence and low population progression rates consistent with the early 1970s. Introducing only the observed, rising obesity prevalence, we calculated the incremental incidence caused by obesity. We compared these with EAC incidence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry to determine obesity's contribution to the rise therein. Incidences were converted to absolute numbers of cases using U.S. population data. Using constant obesity prevalence, we projected a total of 30,555 EAC cases cumulatively over 1973 to 2005 and 1,151 in 2005 alone. Incorporating the observed obesity trend resulted in 35,767 cumulative EACs and 1,608 in 2005. Estimates derived from SEER data showed 111,223 cumulative and 7,173 cases in 2005. We conclude that the rise in obesity accounted for 6.5% of the increase in EAC cases that occurred from 1973 to 2005 and 7.6% in the year 2005. Using published OR for EAC among obese individuals, we found that only a small percentage of the rise in EAC incidence is attributable to secular trends in obesity. Other factors, alone and in combination, should be explored as causes of the EAC epidemic.


Risk scoring for setting priorities in a monitoring of antimicrobial resistance in meat and meat products.
Meat and meat products can be contaminated with different species of bacteria resistant to various antimicrobials. The human health risk of a type of meat or meat product carry by emerging antimicrobial resistance depends on (i) the prevalence of contamination with resistant bacteria, (ii) the human health consequences of an infection with a specific bacterium resistant to a specific antimicrobial and (iii) the consumption volume of a specific product. The objective of this study was to compare the risk for consumers arising from their exposure to antibiotic resistant bacteria from meat of four different types (chicken, pork, beef and veal), distributed in four different product categories (fresh meat, frozen meat, dried raw meat products and heat-treated meat products). A semi-quantitative risk assessment model, evaluating each food chain step, was built in order to get an estimated score for the prevalence of Campylobacter spp., Enterococcus spp. and Escherichia coli in each product category. To assess human health impact, nine combinations of bacterial species and antimicrobial agents were considered based on a published risk profile. The combination of the prevalence at retail, the human health impact and the amount of meat or product consumed, provided the relative proportion of total risk attributed to each category of product, resulting in a high, medium or low human health risk. According to the results of the model, chicken (mostly fresh and frozen meat) contributed 6.7% of the overall risk in the highest category and pork (mostly fresh meat and dried raw meat products) contributed 4.0%. The contribution of beef and veal was of 0.4% and 0.1% respectively. The results were tested and discussed for single parameter changes of the model. This risk assessment was a useful tool for targeting antimicrobial resistance monitoring to those meat product categories where the expected risk for public health was greater.


Measuring participation for persons with mental illness: a systematic review assessing relevance of existing scales for low and middle income countries.
Participation is increasingly becoming an important outcome for assessment in many fields, including development, disability and policy implementation. However, selecting specific instruments to measure participation has been a significant problem due to overlapping conceptual definitions and use of different theories. The objective of this paper is to identify participation instruments, examine theories/definition supporting their use and highlight scales for use in low and middle-income countries for persons with mental illness. A systematic literature review was conducted to identify instruments intended to measure participation for individuals with severe mental illness. The search was limited to peer-reviewed articles published in English between 2003 and 2014. Instruments that measured related concepts of well-being, quality of life and social functioning were also identified and screened for items that pertained to participation, defined as empowerment and collective capabilities. Five scales met established criteria for assessing participation and were determined to contain questions measuring empowerment and/or collective capabilities. However, each scale largely assessed individual functioning and capacity, while neglecting collective aspects of the community. All scales were developed in high-income countries and none were used in low and middle-income countries. There is an urgent need for participation scales to focus on empowerment as well as collective capabilities. Further, development of participation scales should clearly delineate theoretical foundations and concepts used. Finally, participation scales used in low and middle income countries should consider how contextual factors like medicine, poverty and disability, particularly with regards to mental illness, impact content of the scale.


High-Performance Synthesis of Phosphorus-Doped Graphene Materials and Stabilization of Phosphoric Micro- and Nanodroplets.
A thermally induced cascade process leading to the formation of stable micro- and nanometer-size phosphoric droplets was developed starting from a molecular precursor. Microwave-induced pyrolysis of 1,2,3,4,5-pentaphenylphosphole oxide proceeded through a series of subsequent transformations involving formation of phosphorus-doped graphene oxide layers, seeding of carbon surface with phosphorus centers, and assembling of stable droplets. A complex nanostructured organization of the material was established in a remarkably short time of 3 min, and the process was performed in a thermally induced manner using microwave irradiation. High stability of the liquid phosphoric structures on the surface of doped graphene oxide over a few-month period was demonstrated, as well as under challenging conditions in organic solvents (chloroform, methylene chloride, or toluene media) and even under sonication. Detailed examination of this material by electron microscopy and a number of analytical methods showed its unique organization at the nanoscale, whereas computational modeling revealed unusually strong binding of phosphorus oxide P4O10 to the graphene surface. The study demonstrates a fascinating opportunity to access a complex nanostructured multicomponent material from a single and easily available molecular precursor.


The effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder: A randomized clinical trial.
Different studies have been conducted to find the best adjuvant therapies for depression management. There are controversies over the effects of aspirin as an adjuvant therapy for depression. To determine the effects of combined sertraline and aspirin therapy on depression severity among patients with major depressive disorder. This randomized clinical trial was conducted at Kargarnejad Psychiatric Hospital in Kashan, Isfahan, Iran, from September 1, 2016 to November 1, 2016. The study participants included 100 patients with major depressive disorder who were assigned to aspirin and placebo groups by the use of computer-generated random numbers. Patients in these groups respectively received sertraline-aspirin and sertraline-placebo for eight consecutive weeks. Patients were prescribed 80 milligrams of aspirin twice a day. Also, sertraline was administered at a dose of 50-200 milligrams daily. Beck Depression Inventory was employed for depression severity assessment at four time points, namely before, two, four, and eight weeks after the beginning of the intervention. Medication side effects were also assessed eight weeks after the beginning of the intervention. Data were analyzed by SPSS version 12.0, using Chi-square and the Independent-samples t-test (α=0.05). Both groups were matched in terms of age (p=0.46), gender (p=0.539), and depression severity (p=0.509, with mean score 33.5±4.1 vs. 32.8±5.9) at baseline. However, depression scores were reduced significantly four and eight weeks after initiation of therapy just in the sertraline-aspirin group (p<0.05). As an adjuvant therapy, aspirin can reduce depression severity among patients with major depressive disorder. Yet, further studies are needed to prove the effectiveness of aspirin and other anti-inflammatory agents in reducing depression severity. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2016082829556N1. The authors received financial support from Research Deputy of Kashan University of Medical Sciences, Kashan, Isfahan, Iran.


Impact of darker, intermediate and lighter phenotypes of body melanization on desiccation resistance in Drosophila melanogaster.
A possible link between melanization and desiccation resistance can be inferred if within population differences in melanization find significant correlations with desiccation resistance and its mechanistic basis i.e. rate of water loss/hr. Accordingly, darker, intermediate and lighter phenotypes of body melanization were analyzed in wild and laboratory reared Drosophila melanogaster L. (Diptera: Clyclorrapha) populations from highland and lowland sites located in close proximity at five different latitudinal locations (11.15 degrees N to 31.06 degrees N) within the Indian subcontinent. In large population samples, occurrence of significant within population variability made it possible to assort non-overlapping phenotypes of body coloration (i.e. lighter (< 25%), intermediate (30 to 40%) and darker (> 45%)) for all the populations which were further investigated for desiccation resistance and rate of water loss/hr. Significantly, higher desiccation resistance but much reduced rate of water loss/hr were observed in darker and intermediate phenotypes in all the populations. By contrast, lighter phenotypes exhibited lower desiccation tolerance but higher rate of water loss/hr. A regression analysis between traits provided similar slope values for wild and laboratory populations. For all three physiological traits, predicted trait values from multiple regression analysis as a simultaneous function of annual average temperature and relative humidity, matched the observed values. We infer that parallel changes in melanization and desiccation resistance may result from decreasing annual average temperature and relative humidity along increasing latitude as well as altitude on the Indian subcontinent.


Innate-like CD8+ T-cells and NK cells: converging functions and phenotypes.
New data in the worlds of both innate-like CD8+ T-cells and natural killer (NK) cells have, in parallel, clarified some of the phenotypes of these cells and also their associated functions. While these cells are typically viewed entirely separately, the emerging innate functions of T-cells and, similarly, the adaptive functions of NK cells suggest that many behaviours can be considered in parallel. In this review we compare the innate functions of CD8+ T-cells (especially mucosal-associated invariant T-cells) and those of NK cells, and how these relate to expression of phenotypic markers, especially CD161 and CD56.


Ocular Biometric Diurnal Rhythms in Emmetropic and Myopic Adults.
To investigate diurnal variations in anterior and posterior segment biometry and assess differences between emmetropic and myopic adults. Healthy subjects (n = 42, 23-41 years old) underwent biometry and spectral-domain optical coherence tomography imaging (SD-OCT) every 4 hours for 24 hours. Subjects were in darkness from 11:00 PM to 7:00 AM. Central corneal thickness, corneal power, anterior chamber depth, lens thickness, vitreous chamber depth, and axial length were measured. Thicknesses of the total retina, photoreceptor outer segments + RPE, photoreceptor inner segments, and choroid over a 6-mm annulus were determined. All parameters except anterior chamber depth demonstrated significant diurnal variations, with no refractive error differences. Amplitude of choroid diurnal variation correlated with axial length (P = 0.05). Amplitude of axial length variation (35.71 ± 19.40 μm) was in antiphase to choroid variation (25.65 ± 2.01 μm, P < 0.001). The central 1-mm retina underwent variation of 5.03 ± 0.23 μm with a peak at 12 hours (P < 0.001), whereas photoreceptor outer segment + RPE thickness peaked at 4 hours and inner segment thickness peaked at 16 hours. Diurnal variations in retina and choroid were observed in the 3- and 6-mm annuli. Diurnal rhythms in anterior and posterior segment biometry were observed over 24 hours in adults. Differences in baseline parameters were found between refractive error groups, and choroid diurnal variation correlated with axial length. The retina and choroid exhibited diurnal thickness variations in foveal and parafoveal regions.


Evaluation of diffuse pollution model applications in EUROHARP catchments with limited data.
The application of diffuse pollution models included in EUROHARP encompassed varying levels of parameterisation and approaches to the preparation of input data depending on the model and modelling team involved. Modellers consistently faced important decisions in relation to data interpretation, especially in those catchments with unfamiliar physical or climatic characteristics, where catchment conditions were beyond the range for which a particular model was originally developed, or where only limited input data were available. In addition to a broad discussion of data issues, this paper compares the performance of the four sub-annual output models tested in EUROHARP (EveNFlow, NL-CAT, SWAT and TRK) in three test catchments without the modelling teams having sight of measured flow and nitrate concentration data. Model performance in this "blind test" indicate that the range of predictions generated by any individual models pre and post calibration exceed the differences between the estimates yielded by all four models. Comparison of Analysis of Variance (ANOVA) statistics for simulated and observed flow, concentration and loads underscores the benefits of calibration for these intermediate and complex model formulations. Interpretation of input data (e.g. rainfall interpolation method and pedotransfer functions selected) appeared equally (or more) important than process representation. In the absence of calibration data, modeller unfamiliarity with a particular catchment and its environmental processes sometimes resulted in questionable assumptions and input errors which highlight the problems facing modellers charged with implementing policies under the Water Framework Directive (2000/60/EC) in poorly monitored catchments. Catchment data owners and modellers must therefore work more closely given that the output from diffuse pollution models is clearly modeller-limited as well as model-limited.


Characteristics of 252 patients with bronchopulmonary neuroendocrine tumours treated at the Copenhagen NET Centre of Excellence.
Bronchopulmonary neuroendocrine tumours are divided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC). To thoroughly describe a cohort of 252 patients with TC, AC and LCNEC (SCLC excluded). Collection of data from 252 patients referred to and treated at Rigshospitalet 2008-2016. Data was collected from electronic patient files and our prospective NET database. Statistics were performed in SPSS. 162 (64%) had TC, 29 (12%) had AC and 61 (24%) had LCNEC. Median age at diagnosis was 69 years (range: 19-89) with no difference between genders. Thoraco-abdominal CT was performed in all patients at diagnosis. FDG-PET/CT was performed in 207 (82%) at diagnosis and was positive in 95% of the entire cohort, with no difference between tumour types. Synaptophysin was positive in 98%, chromogranin A in 92% and CD56 in 97%. Mean Ki67 index was 5% in TC, 16% in AC and 69% in LCNEC (p < 0.001). Metastatic disease was found in 4% of TC, 27% of AC and 58% of LCNEC at time of initial diagnosis (p < 0.001). In total 179 patients (71%) underwent surgical resection; TC: 87%, AC: 72% and LCNEC: 28% (p < 0.001). Of the resected patients, 11 (6%) had recurrence. Five-year survival rate was 88% for TC, 63% for AC and 20% for LCNEC. In this comprehensive study of a cohort of 252 patients, one of the largest until date, with TC, AC and LCNEC, the gender distribution showed female predominance with 68%. FDG-PET/CT was positive in 95% of the patients independent of tumour type, which confirms that FDG-PET/CT should be a part of the preoperative work-up for TC, AC and LCNEC. Tumour type was the single most potent independent prognostic factor.