Functional Significance of Labellum Pattern Variation in a Sexually Deceptive Orchid (Ophrys heldreichii): Evidence of Individual Signature Learning Effects.
Mimicking female insects to attract male pollinators is an important strategy in sexually deceptive orchids of the genus Ophrys, and some species possess flowers with conspicuous labellum patterns. The function of the variation of the patterns remains unresolved, with suggestions that these enhance pollinator communication. We investigated the possible function of the labellum pattern in Ophrys heldreichii, an orchid species in which the conspicuous and complex labellum pattern contrasts with a dark background. The orchid is pollinated exclusively by males of the solitary bee, Eucera berlandi. Comparisons of labellum patterns revealed that patterns within inflorescences are more similar than those of other conspecific plants. Field observations showed that the males approach at a great speed and directly land on flowers, but after an unsuccessful copulation attempt, bees hover close and visually scan the labellum pattern for up to a minute. Learning experiments conducted with honeybees as an accessible model of bee vision demonstrated that labellum patterns of different plants can be reliably learnt; in contrast, patterns of flowers from the same inflorescence could not be discriminated. These results support the hypothesis that variable labellum patterns in O. heldreichii are involved in flower-pollinator communication which would likely help these plants to avoid geitonogamy.


The need for electronic noses for environmental odour exposure assessment.
This paper focuses on the opportunities for using electronic noses for odour exposure assessment purposes, especially in cases where dispersion modelling is not applicable. Such cases include, for instance, those sources where a detailed characterisation and quantification of the odour emissions for every hour of the simulation time domain is particularly difficult, due to the nature of the source or to the variability of the emissions over time. In such situations, it is useful to determine odour exposure directly at receptors instead. This paper critically discusses the state of the art of electronic nose technology as far as its application to the determination of odour exposure at receptors is concerned. One example of electronic nose application to the monitoring of odours from an Italian municipal solid waste (MSW) landfill is reported, in order to discuss the instrument's potential and limits. The monitoring results are represented by the number of measures that are classified in a specific olfactory class; this information allows the odour exposure at each monitoring site in terms of odour detection frequency to be determined. Besides a quantification of the odour episodes, electronic noses allowed the identification of the landfill gas as the monitored landfill major odour source.


X-linked hypophosphatemia attributable to pseudoexons of the PHEX gene.
X-linked hypophosphatemia is commonly caused by mutations of the coding region of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). However, such PHEX mutations are not detected in approximately one third of X-linked hypophosphatemia patients who may harbor defects in the noncoding or intronic regions. We have therefore investigated 11 unrelated X-linked hypophosphatemia patients in whom coding region mutations had been excluded, for intronic mutations that may lead to mRNA splicing abnormalities, by the use of lymphoblastoid RNA and RT-PCRs. One X-linked hypophosphatemia patient was found to have 3 abnormally large transcripts, resulting from 51-bp, 100-bp, and 170-bp insertions, all of which would lead to missense peptides and premature termination codons. The origin of these transcripts was a mutation (g to t) at position +1268 of intron 7, which resulted in the occurrence of a high quality novel donor splice site (ggaagg to gtaagg). Splicing between this novel donor splice site and 3 preexisting, but normally silent, acceptor splice sites within intron 7 resulted in the occurrences of the 3 pseudoexons. This represents the first report of PHEX pseudoexons and reveals further the diversity of genetic abnormalities causing X-linked hypophosphatemia.


Structure-guided drug design identifies a BRD4-selective small molecule that suppresses HIV.
HIV integrates its provirus into the host genome and establishes latent infection. Antiretroviral therapy (ART) can control HIV viremia, but cannot eradicate or cure the virus. Approaches targeting host epigenetic machinery to repress HIV, leading to an aviremic state free of ART, are needed. Bromodomain and extraterminal (BET) family protein BRD4 is an epigenetic reader involved in HIV transcriptional regulation. Using structure-guided drug design, we identified a small molecule (ZL0580) that induced epigenetic suppression of HIV via BRD4. We showed that ZL0580 induced HIV suppression in multiple in vitro and ex vivo cell models. Combination treatment of cells of aviremic HIV-infected individuals with ART and ZL0580 revealed that ZL0580 accelerated HIV suppression during ART and delayed viral rebound after ART cessation. Mechanistically different from the BET/BRD4 pan-inhibitor JQ1, which nonselectively binds to BD1 and BD2 domains of all BET proteins, ZL0580 selectively bound to BD1 domain of BRD4. We further demonstrate that ZL0580 induced HIV suppression by inhibiting Tat transactivation and transcription elongation as well as by inducing repressive chromatin structure at the HIV promoter. Our findings establish a proof of concept for modulation of BRD4 to epigenetically suppress HIV and provide a promising chemical scaffold for the development of probes and/or therapeutic agents for HIV epigenetic silencing.


Prevalence and Severity of Dementia in Nursing Home Residents.
The aim of this study was to compare the presence and severity of dementia in two large cross-sectional samples of nursing home residents from 2004/2005 and 2010/2011. Demographic information as well as data on the type of nursing home unit, length of stay before assessment, physical health, regularly used prescribed drugs and Clinical Dementia Rating scale scores were used in the analyses. Logistic and linear regression models for hierarchical data were estimated. The odds of the occurrence and of a greater severity of dementia were higher in 2010/2011 than in 2004/2005. Independent of the time of study, married men had more severe dementia than single men, and single women had more severe dementia than single men. The findings may reflect the increase in the need for more nursing home beds designed for people with dementia between 2004/2005 and 2010/2011.


Label-free electrochemical monitoring of DNA ligase activity.
This study presents a simple, label-free electrochemical technique for the monitoring of DNA ligase activity. DNA ligases are enzymes that catalyze joining of breaks in the backbone of DNA and are of significant scientific interest due to their essential nature in DNA metabolism and their importance to a range of molecular biological methodologies. The electrochemical behavior of DNA at mercury and some amalgam electrodes is strongly influenced by its backbone structure, allowing a perfect discrimination between DNA molecules containing or lacking free ends. This variation in electrochemical behavior has been utilized previously for a sensitive detection of DNA damage involving the sugar-phosphate backbone breakage. Here we show that the same principle can be utilized for monitoring of a reverse process, i.e., the repair of strand breaks by action of the DNA ligases. We demonstrate applications of the electrochemical technique for a distinction between ligatable and unligatable breaks in plasmid DNA using T4 DNA ligase, as well as for studies of the DNA backbone-joining activity in recombinant fragments of E. coli DNA ligase.


Evolutionary study of duplications of the miRNA machinery in aphids associated with striking rate acceleration and changes in expression profiles.
The sequencing of the genome of the pea aphid Acyrthosiphon pisum revealed an unusual expansion of the miRNA machinery, with two argonaute-1, two dicer-1 and four pasha gene copies. In this report, we have undertaken a deeper evolutionary analysis of the phylogenetic timing of these gene duplications and of the associated selective pressures by sequencing the two copies of ago-1 and dcr-1 in different aphid species of the subfamily Aphidinae. We have also carried out an analysis of the expression of both copies of ago-1 and dcr-1 by semi-quantitative PCR in different morphs of the pea aphid life cycle. The analysis has shown that the duplication of ago-1 occurred in an ancestor of the subfamily Aphidinae while the duplication of dcr-1 appears to be more recent. Besides, it has confirmed a pattern of one conserved copy and one accelerated copy for both genes, and has revealed the action of positive selection on several regions of the fast-evolving ago-1b. On the other hand, the semi-quantitative PCR experiments have revealed a differential expression of these genes between the morphs of the parthenogenetic and the sexual phases of Acyrthosiphon pisum. The discovery of these gene duplications in the miRNA machinery of aphids opens new perspectives of research about the regulation of gene expression in these insects. Accelerated evolution, positive selection and differential expression affecting some of the copies of these genes suggests the possibility of a neofunctionalization of these duplicates, which might play a role in the display of the striking phenotypic plasticity of aphids.


Oil-soluble dyes for marking Spodoptera frugiperda (Lepidoptera: Noctuidae).
Although various biological aspects of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) have been examined, adult movement and dispersal of this insect pest is not well understood. Release-recapture techniques by using marked insects is a useful approach for dispersal studies; however, the marking technique should not significantly affect insect biology or behavior. Therefore, the effect of different concentrations of oil-soluble dyes (Solvent Blue 35 [C.I. 61554], Sudan Red 7B [C.I. 26050], Sudan Black B [26150], Sudan Orange G [C.I. 11920], and Sudan I 103624 [C.I. 12055]) on development, mortality, and fecundity of S. frugiperda was evaluated. Dyes were added to artificial diet used to feed larvae. Larval and pupal development and mortality, adult longevity, and female fecundity were evaluated. High concentrations (400 and 600 ppm) of all dyes led to longer larval and pupal stages. Adult life span and number of eggs were not affected by the dyes. Sudan Red 7B marked both adults and eggs very well. Solvent Blue 35 marked both adults and eggs, but the blue-marked eggs could not be distinguished from some bluish eggs laid by nonlabeled females. Adults and eggs were not adequately marked by the Sudan Black B, Sudan Orange G, and Sudan I 103624 (a yellow dye).


Dispersion shifts in optical nanowires with thin dielectric coatings.
Based on exact solutions of Maxwell's equations of a 3-layer-structured cylindrical waveguide, we calculated dispersion shifts in thin-dielectric-coated optical nanowires. Typical parameters of silica and silicon nanowires are used for numerical simulations. It shows that, the dispersion of a nanowire waveguide can be made highly sensitive to the thickness and index of the coating layer, and a thin coat may lead to considerable dispersion shift of the guided light. For example, in a 300-nm-diameter silicon nanowire, a 1% decrease in diameter of the silicon core by oxidation of silicon into silica shell leads to a 34% decrease in dispersion at 1450-nm wavelength. Results presented in this work suggest the possibility of tuning waveguide dispersions of optical nanowires by coating thin dielectric layers.


Task Delegation and Burnout Trade-offs Among Primary Care Providers and Nurses in Veterans Affairs Patient Aligned Care Teams (VA PACTs).
Appropriate delegation of clinical tasks from primary care providers (PCPs) to other team members may reduce employee burnout in primary care. However, (1) the extent to which delegation occurs within multidisciplinary teams, (2) factors associated with greater delegation, and (3) whether delegation is associated with burnout are all unknown. We performed a national cross-sectional survey of Veterans Affairs (VA) PCP-nurse dyads in Department of VA primary care clinics, 4 years into the VA's patient-centered medical home initiative. PCPs reported the extent to which they relied on other team members to complete 15 common primary care tasks; paired nurses reported how much they were relied on to complete the same tasks. A composite score of task delegation/reliance was developed by taking the average of the responses to the 15 questions. We performed multivariable regression to explore predictors of task delegation and burnout. Among 777 PCP-nurse dyads, PCPs reported delegating tasks less than nurses reported being relied on (PCP mean ± standard deviation composite delegation score, 2.97± 0.64 [range, 1-4]; nurse composite reliance score, 3.26 ± 0.50 [range, 1-4]). Approximately 48% of PCPs and 35% of nurses reported burnout. PCPs who reported more task delegation reported less burnout (odds ratio [OR], 0.62 per unit of delegation; 95% confidence interval [CI], 0.49-0.78), whereas nurses who reported being relied on more reported more burnout (OR, 1.83 per unit of reliance; 95% CI, 1.33-2.5). Task delegation was associated with less burnout for PCPs, whereas task reliance was associated with greater burnout for nurses. Strategies to improve work life in primary care by increasing PCP task delegation must consider the impact on nurses.


Assessing lung transplantation ischemia-reperfusion injury by microcomputed tomography and ultrashort echo-time magnetic resonance imaging in a mouse model.
Ischemia-reperfusion injury (I/R) is a common early complication after lung transplantation. The purpose of this study was to compare ultrashort echo-time (UTE) sequences in magnetic resonance imaging (MRI) with a microcomputed tomography (micro-CT) reference standard for detection of I/R injury in a lung transplantation mouse model. Six mice (C57BL/6) underwent orthotopic lung transplantation using donor grafts that were exposed to 6-hour cold ischemia. Imaging was performed within 24 hours after the transplantation with high-resolution micro-CT (tube voltage, 50 kV; current, 500 mA; aluminum filter, 0.5 mm; voxel size, 35 × 35 × 35 μm³) and small-animal MRI at 4.7 T with a linearly polarized whole-body mouse coil. The imaging protocol comprised radial 3-dimensional UTE sequences with different echo times (repetition time, 8 milliseconds; echo time, 50/75/100/500/1500/3000/4000/5000 μs; voxel size, 350 × 350 × 350 μm³). Images were assessed visually and through calculation of contrast-to-noise ratio (CNR) values. Calculated S0 values and T2* transverse relaxation times (MRI) of lung parenchyma were compared with Hounsfield unit (HU) density in micro-CT images. Receiver operating characteristic curves and area under the curve values were calculated for comparison of diagnostic power. All samples underwent a histologic examination. The results of both UTE MRI and micro-CT showed an excellent depiction of pulmonary infiltration due to I/R injury, with MRI exhibiting a significantly higher CNR (mean [SD] CNR MRI, 19.7 [8.0]; mean [SD] CNR micro-CT, 10.3 [2.5]; P < 0.001). Measured parametrical values were as follows: mean (SD) HU, -416 (120); mean (SD) S0 value, 1655 (440); mean (SD) T2*, 895 (870) μs for the non-transplanted right lung and mean (SD) HU, 29 (35); mean (SD) S0 value, 2310 (300); and mean (SD) T2*, 4550 (3230) μs for the transplanted left lung. Slight infiltration could be better discriminated with micro-CT, whereas, in strong infiltration, a better contrast was provided by UTE MRI. The area under the curve values resulting from the receiver operating characteristic curve analysis were 0.99 for HU density, 0.89 for S₀, 0.96 for T2*, and 0.98 for the combination of S₀ and T2*. Results show that MRI of the lung has a similar diagnostic power compared with that of micro-CT regarding the detection of I/R injury after experimental lung transplantation. Both modalities provide complementary information in the assessment of dense and slight infiltration in the early phase after lung transplantation. Therefore, UTE MRI seems to be a promising addition to computed tomographic imaging in the assessment of I/R injury after lung transplantation.


Effect of Power Line Interference on Microphone Calibration Measurements Made at or Near Harmonics of the Power Line Frequency.
The electrical measurements required during the primary calibrations of laboratory standard microphones by the reciprocity method can be influenced by power line interference. Because of this influence, the protocols of international inter-laboratory key comparisons of microphone calibrations usually have not included measurements at power line frequencies. Such interference has been observed in microphone output voltage measurements made with a microphone pressure reciprocity calibration system under development at NIST. This system was configured for a particular type of standard microphone in such a way that measurements of relatively small signal levels, which are more susceptible to the effect of power line interference, were required. This effect was investigated by acquiring microphone output voltage measurement data with the power line frequency adjusted to move the frequency of the interference relative to the center frequency of the measurement system passband. These data showed that the effect of power line interference for this system configuration can be more than one percent at test frequencies harmonically related to the power line frequency. These data also showed that adjusting the power line frequency to separate the interference and test frequencies by as little as 1.0 Hz can reduce the effect of the interference by at least an order of magnitude. Adjustment of the power line frequency could enable accurate measurements at test frequencies that otherwise might be avoided.


Purification of Bone Marrow Clonal Cells from Patients with Myelodysplastic Syndrome via IGF-IR.
Malignant clonal cells purification can greatly benefit basic and clinical studies in myelodysplastic syndrome (MDS). In this study, we investigated the potential of using type 1 insulin-like growth factor receptor (IGF-IR) as a marker for purification of malignant bone marrow clonal cells from patients with MDS. The average percentage of IGF-IR expression in CD34+ bone marrow cells among 15 normal controls was 4.5%, 70% of which also express the erythroid lineage marker CD235a. This indicates that IGF-IR mainly express in erythropoiesis. The expression of IGF-IR in CD34+ cells of 55 MDS patients was significantly higher than that of cells from the normal controls (54.0 vs. 4.5%). Based on the pattern of IGF-IR expression in MDS patients and normal controls, sorting of IGF-IR-positive and removal of CD235a-positive erythroid lineage cells with combination of FISH detection were performed on MDS samples with chromosomal abnormalities. The percentage of malignant clonal cells significantly increased after sorting. The enrichment effect was more significant in clonal cells with a previous percentage lower than 50%. This enrichment effect was present in samples from patients with +8, 5q-/-5, 20q-/-20 or 7q-/-7 chromosomal abnormalities. These data suggest that IGF-IR can be used as a marker for MDS bone marrow clonal cells and using flow cytometry for positive IGF-IR sorting may effectively purify MDS clonal cells.


Evaluation of Health Outcomes with Etanercept Treatment in Patients with Early Nonradiographic Axial Spondyloarthritis.
Analyses were conducted to examine the baseline burden of illness and compare the effect of etanercept (ETN) versus placebo (PBO) on quality of life (QOL) in patients with nonradiographic axial spondyloarthritis (nr-axSpA) who failed nonsteroidal antiinflammatory drugs (NSAID). Patients fulfilling the Assessment of Spondyloarthritis International Society axSpA criteria, not meeting the modified New York criteria for ankylosing spondylitis (AS), who were symptomatic 3 months to 5 years, with a Bath AS Disease Activity Index score ≥ 4, and failed ≥ 2 NSAID were randomized to ETN 50 mg weekly or PBO (double-blind) for 12 weeks, followed by open-label ETN 50 mg for 92 weeks. Stable NSAID were allowed throughout our study. QOL outcomes over 24 weeks were analyzed using ANCOVA models. At baseline, Multidimensional Fatigue Inventory (MFI; ETN mean 14.7, PBO mean 15.0), EQ-5D utility (0.52, 0.57), EQ-5D visual analog scale (56.5, 56.4), and Medical Outcomes Study (MOS) Sleep Index II (45.5, 48.1) were worse than population norms (6.6-8.0, 0.86, 82.5, and 25.8, respectively). At Week 12, Bath AS Patient Global Score, nocturnal and average back pain, MOS Short Form-36 (SF-36) physical component, and Work Productivity and Activity Index (WPAI) presenteeism and activity impairment favored ETN (p < 0.05). Nonsignificant improvements for ETN were seen in other WPAI domains, MFI, MOS-Sleep Index I and II, Hospital Anxiety and Depression Scale, EQ-5D utility score, and SF-36 mental component (p > 0.05). At Week 24, patients in the PBO group who had switched to ETN at Week 12 showed improvement in most QOL assessments, similar to that seen in patients receiving ETN for 24 weeks. Improvements favored ETN in QOL and productivity measures, with limited improvement on general QOL measures. Short disease duration, a short PBO-controlled period, and a wide range of QOL scores at baseline may have influenced improvements.


Parapagus (dicephalus, tetrabrachius, dipus) conjoined twins and their rehabilitation.
A case of female parapagus conjoined twins living as unseparated is presented in this report. The twins had two heads, four arms and two legs. As a result of their fusion, operative care had been considered to be unacceptable, and the family had refused to take care of them. At three years of age, they were referred to the Rehabilitation Department with the complaint of inability to walk. While designing the rehabilitation program, somatosensory evoked potential evaluation was performed and showed that twin 1 controlled the right leg and twin 2 controlled the left. The program consisted of coordinated pacing training by verbal commands, upper and lower extremity reeducation, and balance and coordination exercises. After two months of inpatient rehabilitation, they were able to walk independently with a specially designed walker. Currently, the twins are 11 years old with normal academic achievement, and they are able to walk, run and climb the stairs independently.


A turquoise fluorescence lifetime-based biosensor for quantitative imaging of intracellular calcium.
The most successful genetically encoded calcium indicators (GECIs) employ an intensity or ratiometric readout. Despite a large calcium-dependent change in fluorescence intensity, the quantification of calcium concentrations with GECIs is problematic, which is further complicated by the sensitivity of all GECIs to changes in the pH in the biological range. Here, we report on a sensing strategy in which a conformational change directly modifies the fluorescence quantum yield and fluorescence lifetime of a circular permutated turquoise fluorescent protein. The fluorescence lifetime is an absolute parameter that enables straightforward quantification, eliminating intensity-related artifacts. An engineering strategy that optimizes lifetime contrast led to a biosensor that shows a 3-fold change in the calcium-dependent quantum yield and a fluorescence lifetime change of 1.3 ns. We dub the biosensor Turquoise Calcium Fluorescence LIfeTime Sensor (Tq-Ca-FLITS). The response of the calcium sensor is insensitive to pH between 6.2-9. As a result, Tq-Ca-FLITS enables robust measurements of intracellular calcium concentrations by fluorescence lifetime imaging. We demonstrate quantitative imaging of calcium concentrations with the turquoise GECI in single endothelial cells and human-derived organoids.


Transvaginal ultrasonography in first trimester of pregnancy and its comparison with transabdominal ultrasonography.
Examination of pregnant women in the first trimester with transvaginal ultrasonography with the aim to study various fetal development markers, e.g., gestation sac, yolk sac, fetal heart motion, CRL length, and fetal anatomy in both normal and abnormal pregnancies. Comparative evaluation of transvaginal ultrasonography vis-à-vis transabdominal scanning in the study of first trimester of pregnancy and its complications. To assess the relative merits and demerits of transvaginal ultrasonography in comparison with the transabdominal technique. The study will be conducted on 50 females patients during the first trimester of pregnancy. The study population will consist of both normal and abnormal pregnancies. These patients will be included on the basis of suspicion of or proven pregnancy of duration up to 12 weeks from LMP. The evaluation of the patients will include the following: Record of patients obstetrical history and clinical examination, record of pregnancy test and relevant investigations, ultrasonic examination of pregnancy. (a) Transabdominal ultrasound scanning will be done with moderately distended bladder by using real time scanners with low frequency probe (3/3.5 MHz); (b) transvaginal sonography will be done with the real-time sector scanner using high-frequency endovaginal probe (5/7.5 MHz), after the patient voids urine. Relevant images will be taken by using the multiformat automatic camera. In the study of 46 normal intrauterine pregnancies, TVS showed additional information in 36 patients (78.3%) as compared to TAS, in detection of gestation sac, yolk sac, double bleb sign, or better visualization of embryonic anatomy. In the abnormal pregnancy (n=17), TVS provided more information in 11 cases (64.9%), which included detection of embryonic demise, yolk sac, double bleb sign, or subchorionic hemorrhage. Regarding ectopic gestations (n=7), TVS gave additional information in 5 cases (71.4%) which included detection of ectopic fetal pole, yolk sac, decidual cast, adnexal mass, and fluid in cul de sac. In two cases, both TAS and TVS gave equal information. However, in 2 cases TAS demonstrated the extent of intraabdominal fluid better than TVS. The other advantages of TVS over TAS are that there is no need for the patient to have uncomfortably full bladder and time is saved from having to wait for bladder to fill. Thus, the potential preoperative patient can be kept fasting. TVS is also superior in obese patients, in patients with retroverted uterus and it also bypasses obstacles such as bone, gas filled bowel, and extensive pelvic adhesions. The limitations encountered with TVS were limited manoveuribility of probe and because of the unorthodox position and angle of the transducer, correct orientation was difficult initially.


Probiotic Bifidobacterium bifidum G9-1 attenuates 5-fluorouracil-induced intestinal mucositis in mice via suppression of dysbiosis-related secondary inflammatory responses.
Bifidobacterium, a major component of the intestinal microbiota, has been clinically used for the treatment of diarrhoea and constipation. 5-Fluorouracil (5-FU), widely used for cancer chemotherapy, is known to frequently induce intestinal mucositis accompanied by severe diarrhoea. The present study examined the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on 5-FU-induced intestinal mucositis in mice. Intestinal mucositis was induced by repeated administration of 5-FU for 6 days. BBG9-1 was administered orally once daily for 9 days, beginning 3 days before the onset of 5-FU treatment. Repeated administration of 5-FU caused severe intestinal mucositis, characterised by shortening of villi and destruction of crypts, accompanied by increases in intestinal myeloperoxidase activity and inflammatory cytokine expression, body weight loss, and diarrhoea on day 6. Daily administration of BBG9-1 significantly reduced the severity of intestinal mucositis and inflammatory responses and tended to attenuate clinical symptoms. In contrast, BBG9-1 failed to prevent apoptosis induction on day 1 after the first 5-FU administration. The structure of the intestinal microbiota, as analysed by weighted UniFrac distance, was largely altered by 5-FU treatment, but this change was mitigated by daily administration of BBG9-1. Moreover, 5-FU treatment decreased the abundance of Firmicutes and increased the abundance of Bacteroidetes, but these responses were also significantly inhibited by daily administration of BBG9-1. These results suggest that BBG9-1 has an ameliorative effect against 5-FU-induced intestinal mucositis through the attenuation of inflammatory responses via improve dysbiosis. BBG9-1 could be useful for the prevention of intestinal mucositis during cancer chemotherapy.


Classification of different sustainable flood retention basin types.
Using a revised version of a previously published expert classification system, a database of potential Sustainable Flood Retention Basins has been developed for Scotland. The research shows that the majority of small and former (often old) drinking water reservoirs are kept full and their spillways are continuously in operation. Utilising some of the available capacity to contribute to flood control could significantly reduce the costs of complying with the European Union Flood Directive. Furthermore, the application of a previously developed classification model for Baden in Germany for the Scottish data set showed a lower diversity for basins in Scotland due to less developed infrastructure. The classification system appears to be robust and has the potential, with minor modifications, to be applied across Europe. The principle value of this approach is a clear and unambiguous categorisation, based on standard variables, which can help to promote communication and understanding between stakeholders.


Transforming Chaplaincy Requires Transforming Clinical Pastoral Education.
Clinical Pastoral Education (CPE) is a process focused on developing students' personal integration. Outcomes for CPE need to expand to reflect current research in religion and spirituality because religion and spirituality impacts coping, meaning making, decision-making, and health care outcomes. Focusing CPE outcomes on religious/spiritual beliefs and practices used by patients will equip chaplains to provide research-informed spiritual care for families and discipline-specific information for the interdisciplinary team.


Dietary supplement use in the Prostate Cancer Prevention Trial: implications for prevention trials.
Nutrients included in commonly used dietary supplements, such as vitamins C and E, may affect cancer risk. To better understand how supplement use may affect the interpretation of cancer prevention trials, we examined dietary supplement use among participants in the Prostate Cancer Prevention Trial, a double-blind, placebo-controlled trial of the drug finasteride (Proscar) for the primary prevention of prostate cancer. Of 15,387 men who completed food frequency questionnaires and dietary supplement questionnaires, 44.3% used a multivitamin, 35% used single supplements of vitamin C or E, and 10-15% used antioxidant mixtures or single supplements of vitamins A and D, zinc, or beta-carotene at least three times per week. The strongest correlates of supplement use were higher education and lower body mass index (p < 0.001), and whites and Asians were more likely to use multivitamins and single supplements of vitamins C and E than were blacks and Hispanics. Supplement users obtained 87% of their total daily vitamin E intake, 61-64% of vitamins A, C, and D, and about half of beta-carotene, folate, and zinc from supplements. Because supplements, especially antioxidants, may confer independent cancer-preventive effects, analytic models of study findings should include exposure measurement of dietary supplements with appropriate tests for interaction. Our results can be generalized to similar chemoprevention trials.


Role of Pax3 acetylation in the regulation of Hes1 and Neurog2.
Pax3 plays a role in regulating Hes1 and Neurog2 activity and thereby stem cell maintenance and neurogenesis. A mechanism for Pax3 regulation of these two opposing events, during caudal neural tube development, is examined in this study. Pax3 acetylation on C-terminal lysine residues K437 and K475 may be critical for proper regulation of Hes1 and Neurog2. Removal of these lysine residues increased Hes1 but decreased Neurog2 promoter activity. SIRT1 deacetylase may be a key component in regulating Pax3 acetylation. Chromatin immunoprecipitation assays showed that SIRT1 is associated with Hes1 and Neurog2 promoters during murine embryonic caudal neural tube development at E9.5, but not at E12.5. Overexpression of SIRT1 decreased Pax3 acetylation, Neurog2 and Brn3a positive staining. Conversely, siRNA-mediated silencing of SIRT1 increased these factors. These studies suggest that Pax3 acetylation results in decreased Hes1 and increased Neurog2 activity, thereby promoting sensory neuron differentiation.


Leukoencephalopathy, cerebral calcifications and cysts: a family study.
We present a clinical, neuro-radiological and genetic study on a family with members suffering from an autosomal dominantly inherited syndrome characterised by epilepsy, cerebral calcifications and cysts, bone abnormalities; progressive neuro-cognitive deterioration and paranasal sinusitis. This syndrome shares several features with leukoencephalopathy with calcifications and cysts also called Labrune syndrome and the condition of cerebroretinal microangiopathy with calcifications and cysts (CRMCC; Coats plus syndrome). Genetic studies in this family did not reveal mutations in the CTC1 gene defected in CRMCC. We interpret our results as those supporting recent findings that despite clinical similarities, late-onset Labrune and Coats plus syndrome might be distinct entities. This family may have Labrune syndrome or a yet unclassified entity; exploration of similar cases could help classifying this one, and related conditions.


Identification of two highly sialylated human tear-fluid DMBT1 isoforms: the major high-molecular-mass glycoproteins in human tears.
Human open eye tear fluid was separated by low-percentage SDS/PAGE to detect high-molecular-mass protein components. Two bands were found with apparent molecular masses of 330 and 270 kDa respectively. By peptide-mass fingerprinting after tryptic digestion, the proteins were found to be isoforms of the DMBT1 gene product, with over 30% of the predicted protein covered by the tryptic peptides. By using gradient SDS/agarose/polyacrylamide composite gel electrophoresis and staining for glycosylation, it was shown that the two isoforms were the major high-molecular-mass glycoproteins of >200 kDa in human tear fluid. Western blotting showed that the proteins expressed sialyl-Le(a). After the release of oligosaccharides by reductive beta-elimination from protein blotted on to PVDF membrane, it was revealed by liquid chromatography-MS that the O-linked oligosaccharides were comprised mainly of highly sialylated oligosaccharides with up to 16 monosaccharide units. A majority of the oligosaccharides could be described by the formula dHex(0-->2)NeuAc(1-->)(x)Hex(x)HexNAc(x)(-ol), x=1-6, where Hex stands for hexose, dHex for deoxyhexose, HexNAc for N-acetylhexosamine and NeuAc for N-acetylneuraminate. The number of sialic acids in the formula is less than 5. Interpretation of collision-induced fragmentation tandem MS confirmed the presence of sialic acid and suggested the presence of previously undescribed structures carrying the sialyl-Le(a) epitopes. Small amounts of neutral and sulphated species were also present. This is the first time that O-linked oligosaccharides have been detected and described from protein variant of the DMBT1 gene.


Isolation and characterization of a Drosophila homologue of mitogen-activated protein kinase phosphatase-3 which has a high substrate specificity towards extracellular-signal-regulated kinase.
A partial C-terminal cDNA sequence of a novel Drosophila mitogen-activated protein kinase phosphatase (MKP), designated DMKP-3, was identified from an epitope expressed sequence tag database, and the missing N-terminal cDNA fragment was cloned from a Drosophila cDNA library. DMKP-3 is a protein of 411 amino acids, with a calculated molecular mass of 45.8 kDa; the deduced amino acid sequence is most similar to that of mammalian MKP-3. Recombinant DMKP-3 produced in Escherichia coli retained intrinsic tyrosine phosphatase activity. In addition, DMKP-3 specifically inhibited extracellular-signal-regulated kinase (ERK) activity, but was without a significant affect on c-Jun N-terminal kinase (JNK) and p38 activities, when it was overexpressed in Schneider cells. DMKP-3 interacted specifically with Drosophila ERK (DERK) via its N-terminal domain. In addition, DMKP-3 specifically inhibited Elk-1-dependent trans-reporter gene expression in mammalian CV1 cells, and dephosphorylated activated mammalian ERK in vitro. DMKP-3 is uniquely localized in the cytoplasm within Schneider cells, and gene expression is tightly regulated during development. Thus DMKP-3 is a Drosophila homologue of mammalian MKP-3, and may play important roles in the regulation of various developmental processes.


Evaluating Serum Markers for Hormone Receptor-Negative Breast Cancer.
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. Death rates have been declining, largely as a result of early detection through mammography and improved treatment, but mammographic screening is controversial because of over-diagnosis of breast disease that might not require treatment, and under-diagnosis of cancer in women with dense breasts. Breast cancer screening could be improved by pairing mammography with a tumor circulating marker, of which there are currently none. Given genomic similarities between the basal breast cancer subtype and serous ovarian cancer, and given our success in identifying circulating markers for ovarian cancer, we investigated the performance in hormone receptor-negative breast cancer detection of both previously identified ovarian serum markers and circulating markers associated with transcripts that were differentially expressed in breast cancer tissue compared to healthy breast tissue from reduction mammaplasties. We evaluated a total of 15 analytes (13 proteins, 1 miRNA, 1 autoantibody) in sera drawn at or before breast cancer surgery from 43 breast cancer cases (28 triple-negative-TN-and 15 hormone receptor-negative-HRN-/ HER2-positive) and 87 matched controls. In the analysis of our whole cohort of breast cancer cases, autoantibodies to TP53 performed significantly better than the other selected 14 analytes showing 25.6% and 34.9% sensitivity at 95% and 90% specificity respectively with AUC: 0.7 (p<0.001). The subset of 28 TN cancers showed very similar results. We observed no correlation between anti-TP53 and the 14 other markers; however, anti-TP53 expression correlated with Body-Mass-Index. It did not correlate with tumor size, positive lymph nodes, tumor stage, the presence of metastases or recurrence. None of the 13 serum proteins nor miRNA 135b identified women with HRN or TN breast cancer. TP53 autoantibodies identified women with HRN breast cancer and may have potential for early detection, confirming earlier reports. TP53 autoantibodies are long lasting in serum but may be affected by storage duration. Autoantibodies to TP53 might correlate with Body-Mass-Index.


Dual regulation of P-glycoprotein expression by trichostatin A in cancer cell lines.
It has been reported that the histone deacetylase inhibitor (iHDAc) trichostatin A (TSA) induces an increase in MDR1 gene transcription (ABCB1). This result would compromise the use of iHDACs in combination with other cytotoxic agents that are substrates of P-glycoprotein (Pgp). It has also been reported the use of alternative promoters by the ABCB1 gene and the existence of a translational control of Pgp protein. Finally, the ABCB1 gene is located in a genetic locus with the nested gene RUNDC3B in the complementary DNA strand, raising the possibility that RUNDC3B expression could interfere with ABCB1 alternative promoter regulation. A combination of RT-PCR, real time RT-PCR, Western blot and drug accumulation assays by flow cytometry has been used in this study. The iHDACs-induced increase in MDR1 mRNA levels is not followed by a subsequent increase in Pgp protein levels or activity in several pancreatic and colon carcinoma cell lines, suggesting a translational control of Pgp in these cell lines. In addition, the MDR1 mRNA produced in these cell lines is shorter in its 5' end that the Pgp mRNA produced in cell lines expressing Pgp protein. The different size of the Pgp mRNA is due to the use of alternative promoters. We also demonstrate that these promoters are differentially regulated by TSA. The translational blockade of Pgp mRNA in the pancreatic carcinoma cell lines could be related to alterations in the 5' end of the MDR1 mRNA in the Pgp protein expressing cell lines. In addition, we demonstrate that the ABCB1 nested gene RUNDC3B expression although upregulated by TSA is independent of the ABCB1 alternative promoter used. The results show that the increase in MDR1 mRNA expression after iHDACs treatment is clinically irrelevant since this mRNA does not render an active Pgp protein, at least in colon and pancreatic cancer cell lines. Furthermore, we demonstrate that TSA in fact, regulates differentially both ABCB1 promoters, downregulating the upstream promoter that is responsible for active P-glycoprotein expression. These results suggest that iHDACs such as TSA may in fact potentiate the effects of antitumour drugs that are substrates of Pgp. Finally, we also demonstrate that TSA upregulates RUNDC3B mRNA independently of the ABCB1 promoter in use.


A novel method for analyzing sequential eye movements reveals strategic influence on Raven's Advanced Progressive Matrices.
Eye movements are an important data source in vision science. However, the vast majority of eye movement studies ignore sequential information in the data and utilize only first-order statistics. Here, we present a novel application of a temporal-difference learning algorithm to construct a scanpath successor representation (SR; P. Dayan, 1993) that captures statistical regularities in temporally extended eye movement sequences. We demonstrate the effectiveness of the scanpath SR on eye movement data from participants solving items from Raven's Advanced Progressive Matrices Test. Analysis of the SRs revealed individual differences in scanning patterns captured by two principal components that predicted individual Raven scores much better than existing methods. These scanpath SR components were highly interpretable and provided new insight into the role of strategic processing on the Raven test. The success of the scanpath SR in terms of prediction and interpretability suggests that this method could prove useful in a much broader context.


Acquisition of motor abilities up to independent walking in very low birth weight preterm infants.
To determine chronological and corrected ages at acquisition of motor abilities up to unaided walking in very low weight preterms and to determine up to what point it is necessary to use corrected age. This was a longitudinal study of preterms with birth weight < 1,500 g and gestational age < or = 34 weeks, free from neurosensory sequelae, selected at the high-risk infants follow-up clinic at the Hospital das Clínicas, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP) in Botucatu, Brazil, between 1998 to 2003, and assessed every 2 months until acquisition of unaided walking. Nine percent of the 155 preterms recruited were excluded from the study, leaving a total of 143 patients. The mean gestational age was 30+/-2 weeks, birth weight was 1,130+/-222 g, 59% were female and 44% were small for gestational age. Preterms achieved head control in their second month, could sit unaided at 7 months and walked at 12.8 months' corrected age, corresponding to the 4th, 9th and 15th months of chronological age. There were significant differences between chronological age and corrected age for all motor abilities. Preterms who were small for their gestational age acquired motor abilities later, but still within expected limits. Very low weight preterms, free from neurosensory disorders, acquired their motor abilities within the ranges expected for their corrected ages. Corrected age should be used until unaided walking is achieved.


Different knockout genotypes of OsIAA23 in rice using CRISPR/Cas9 generating different phenotypes.
We have isolated several Osiaa23 rice mutants with different knockout genotypes, resulting in different phenotypes, which suggested that different genetic backgrounds or mutation types influence gene function. The Auxin/Indole-3-Acetic Acid (Aux/IAA) gene family performs critical roles in auxin signal transduction in plants. In rice, the gene OsIAA23 (Os06t0597000) is known to affect development of roots and shoots, but previous knockouts in OsIAA23 have been sterile and difficult for research continuously. Here, we isolate new Osiaa23 mutants using the CRISPR/Cas9 system in japonica (Wuyunjing24) and indica (Kasalath) rice, with extensive genome re-sequencing to confirm the absence of off-target effects. In Kasalath, mutants with a 13-amino acid deletion showed profoundly greater dwarfing, lateral root developmental disorder, and fertility deficiency, relative to mutants with a single amino acid deletion, demonstrating that those 13 amino acids in Kasalath are essential to gene function. In Wuyunjing24, we predicted that mutants with a single base-pair frameshift insertion would experience premature termination and strong phenotypic defects, but instead these lines exhibited negligible phenotypic difference and normal fertility. Through RNA-seq, we show here that new mosaic transcripts of OsIAA23 were produced de novo, which circumvented the premature termination and thereby preserved the wild-type phenotype. This finding is a notable demonstration in plants that mutants can mask loss of function CRISPR/Cas9 editing of the target gene through de novo changes in alternative splicing.


Long-Term Personalization of an In-Home Socially Assistive Robot for Children With Autism Spectrum Disorders.
Socially assistive robots (SAR) have shown great potential to augment the social and educational development of children with autism spectrum disorders (ASD). As SAR continues to substantiate itself as an effective enhancement to human intervention, researchers have sought to study its longitudinal impacts in real-world environments, including the home. Computational personalization stands out as a central computational challenge as it is necessary to enable SAR systems to adapt to each child's unique and changing needs. Toward that end, we formalized personalization as a hierarchical human robot learning framework (hHRL) consisting of five controllers (disclosure, promise, instruction, feedback, and inquiry) mediated by a meta-controller that utilized reinforcement learning to personalize instruction challenge levels and robot feedback based on each user's unique learning patterns. We instantiated and evaluated the approach in a study with 17 children with ASD, aged 3-7 years old, over month-long interventions in their homes. Our findings demonstrate that the fully autonomous SAR system was able to personalize its instruction and feedback over time to each child's proficiency. As a result, every child participant showed improvements in targeted skills and long-term retention of intervention content. Moreover, all child users were engaged for a majority of the intervention, and their families reported the SAR system to be useful and adaptable. In summary, our results show that autonomous, personalized SAR interventions are both feasible and effective in providing long-term in-home developmental support for children with diverse learning needs.


Interparental conflict and infants' behavior problems: The mediating role of maternal sensitivity.
Although the negative effect of interparental conflict on child behavior problems has been well established, few studies have examined this association during infancy. This study examined the associations between mother-reported interparental conflict and young children's behavior problems over the first 2 years of their lives in a sample of 212 mothers and infants. Two aspects of maternal sensitivity, sensitivity during distressing and nondistressing contexts, were examined as possible mediators between interparental conflict and infants' behavior problems. Results indicated that interparental conflict was associated directly with infants' externalizing problems over time but was associated indirectly with infants' internalizing problems over time via compromised maternal sensitivity within distressing contexts but not through maternal sensitivity within nondistressing contexts. No significant child gender differences were found. Such findings add to a limited body of research suggesting that the early interparental relationship context is relevant for infant adjustment. The salient mediating role of maternal sensitivity within distressing contexts provides important theoretical and practical insights for future studies. (PsycINFO Database Record


Reference values of the 6-minute walk test in healthy Turkish children and adolescents between 11 and 18 years of age.
Normal values of the 6-min walk distance (6MWD) for children have not been well demonstrated. This limits the interpretation of the 6MWD in children. A cross-sectional prospective study was designed. A total of 949 (467 males, 482 females) healthy children were recruited randomly from 7 Turkish secondary schools in Ankara. The 6-min walk tests were conducted according to the American Thoracic Society guidelines. The mean 6MWD decreased between the ages of 12 and 14 y for both boys and girls, and then gradually increased until 17 y of age. In the best fitting and most efficient linear, quadratic, and categorical regression models, the age of the subjects, heart rate after the test, and physical activity level of the subjects were significantly related to the 6MWD. Nevertheless, these variables explained < 20% of the variance in the 6MWD. The 6MWD does not increase in a straight linear fashion from the age of 12 until adulthood. Correlation of the 6MWD with anthropometric features is very weak, so in evaluating the 6MWD, the standard curves should be used.


Astaxanthin protects against oxidative stress and calcium-induced porcine lens protein degradation.
Astaxanthin (ASTX), a carotenoid with potent antioxidant properties, exists naturally in various plants, algae, and seafoods. In this study, we investigated the in vitro ability of ASTX to protect porcine lens crystallins from oxidative damage by iron-mediated hydroxyl radicals or by calcium ion-activated protease (calpain), in addition to the possible underlying biochemical mechanisms. ASTX (1 mM) was capable of protecting lens crystallins from being oxidized, as measured by changes in tryptophan fluorescence, in the presence of a Fenton reaction solution containing 0.2 mM Fe2+ and 2 mM H2O2. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated that beta(high)-crystallin was the most vulnerable protein under these conditions of free radical exposure. The proteolysis of lens crystallins induced by calcium ion-activated calpain was also inhibited by ASTX (0.03-1 mM) as determined by daily measurement of the light-scattering intensity at 405 nm for five consecutive days. ASTX at 1 mM was as potent as a concentration of 0.1 mM calpain inhibitor E64 in protecting the oxidative damage/hydrolysis of porcine crystallins. At a concentration of 1 mM, ASTX provided better protection than the endogenous antioxidant glutathione in terms of suppressing calcium-induced turbidity of lens proteins. Thin-layer chromatography analysis indicated that ASTX interacted with calcium ions to form complexes, which we believe interfere with the hydrolysis of lens crystallins by calcium-activated calpain. This in vitro study shows that ASTX is capable of protecting porcine lens proteins from oxidative insults and degradation by calcium-induced calpain.


Urinary extracellular vesicles as source of biomarkers in kidney diseases.
Most cells physiologically release vesicles as way of intercellular communication. The so-called Extracellular Vesicles (EVs) include exosomes, ectosomes, and apoptotic bodies, which basically differ in their composition and subcellular origin. Specifically, EVs found in urine reflect the state of the urinary system, from podocytes to renal-tubular cells, thus making them an excellent source of samples for the study of kidney physiology and pathology. Several groups have focused on defining biomarkers of kidney-related disorders, from graft rejection to metabolic syndromes. So far, the lack of a standard protocol for EVs isolation precludes the possibility of a proper comparison among the different biomarkers proposed in the literature, stressing the need for validation of these biomarkers not only in larger cohorts of patients but also considering the different methods for EVs isolation. In this review, we aim to gather the current knowledge about EVs-related biomarkers in kidney diseases, with a special emphasis in the methods used to date for EVs enrichment, and discussing the need for more specific protocols of EV isolation in clinical practice.


Guidelines for psychosocial interventions in addictive disorders in India: An introduction and overview.
While guidelines for psychosocial interventions in addictive disorders in India were earlier rooted in clinical experience and global empirical evidence, recently there have been efforts to develop guidelines for intervention based on the local needs assessments of specific populations and more appreciably, a testing of the effectiveness of the interventions. This supplement on psychosocial interventions for addictive disorders covers some of the important aspects of psychosocial interventions in five sections. Section I covers the general principles of management and specific assessment approaches, screening for cognitive dysfunction and assessment of co-morbidities. Section II focuses on specific psychosocial interventions including brief interventions, relapse prevention, cognitive behavioural interventions, psychoanalytical interventions, cognitive rehabilitation, interventions in dual disorders, marital and family therapy, psychosocial interventions for sexual dysfunction and sexual addictions. Section III describes innovative approaches including third wave therapies, video-based relapse prevention, digital technology as a tool for psychosocial interventions as well as psychosocial interventions in technological addictions. The latter part of this section also deals with psychosocial interventions in special populations including children and adolescents, women, sexual minorities and the elderly. Section IV pans into community based psychosocial interventions including community camps and workplace prevention. The need to develop task sharing through the involvement of trained health workers to deliver community and home-based interventions is highlighted. Section V underscores the ethical issues in different aspects of psychosocial intervention and the need for research in this area. Although there is a tendency to formulate addiction in either biomedical or psychosocial terms and to view interventions either as pharmacological or psychosocial, these dichotomies neither exist in the affected individual's mind, nor should be present in the treating clinician. A comprehensive understanding of addiction requires an understanding of the person in his/her environment and needs a personalised holistic approach that addresses the diverse physical/mental health, occupational, legal, social and aftercare needs.


An aerobic eukaryotic parasite with functional mitochondria that likely lacks a mitochondrial genome.
Dinoflagellates are microbial eukaryotes that have exceptionally large nuclear genomes; however, their organelle genomes are small and fragmented and contain fewer genes than those of other eukaryotes. The genus Amoebophrya (Syndiniales) comprises endoparasites with high genetic diversity that can infect other dinoflagellates, such as those forming harmful algal blooms (e.g., Alexandrium). We sequenced the genome (~100 Mb) of Amoebophrya ceratii to investigate the early evolution of genomic characters in dinoflagellates. The A. ceratii genome encodes almost all essential biosynthetic pathways for self-sustaining cellular metabolism, suggesting a limited dependency on its host. Although dinoflagellates are thought to have descended from a photosynthetic ancestor, A. ceratii appears to have completely lost its plastid and nearly all genes of plastid origin. Functional mitochondria persist in all life stages of A. ceratii, but we found no evidence for the presence of a mitochondrial genome. Instead, all mitochondrial proteins appear to be lost or encoded in the A. ceratii nucleus.


Cor triatriatum sinistrum diagnosed in the adulthood: a systematic review.
We performed a systematic review of cor triatriatum sinistrum (CTS) diagnosed in adults. The aim of this review was to describe the clinical presentation, natural history and management of this congenital heart disease. A PubMed literature search for 'cor triatriatum sinistrum' published since 2005 was performed. Included patients were divided into those with and without obstructive membrane physiology. The clinical course differences were compared. A total of 171 published cases were included. The median age at diagnosis was 43 years (IQR, 30-60). Obstructive membrane physiology was observed in 70 (41%), and this patient group was younger at presentation (median age 39 (IQR, 28-52) vs 50 years (IQR, 32-64), p=0.003). Patients with obstructive membrane more frequently had associated cardiac defects (58.6% vs 42.4%, p=0.039). Overall, the most frequent clinical symptom was atrial fibrillation, as this was present in 56 (32.8%) of all patients. CTS-related symptoms were more frequent in patients with obstructive membrane: congestive heart failure (44.3% vs 15.2%, p<0.001), pulmonary hypertension (27.1% vs 6.1%, p<0.001), haemorrhage (8.6% vs 0%, p=0.004) and infections manifestation (8.6% vs 0%, p=0.004).A total of 71 (41.5%) patients with CTS required interventional treatment, mainly within patients with the obstructive membrane (86.8% vs 12.6%, p<0.001). The natural history of CTS most often manifests with symptoms of congestive heart failure. Patients with obstructive membrane most often have associated cardiac defects and higher risk for infections and haemorrhage. The interventional treatment of CTS remains the first choice for obstructive membrane.


Addressing physical activity needs of survivors by developing a community-based exercise program: LIVESTRONG® at the YMCA.
Although methods of cancer detection and treatment have improved, the side effects of treatment can cause profound debilitation that may linger years after treatment ends. Exercise during and after cancer treatment is safe, and it minimizes many of the deleterious physical and emotional side effects. With this evidence in mind, the LIVESTRONG Foundation and the YMCA of the USA collaborated to develop a community-based physical activity program for survivors, LIVESTRONG® at the YMCA. This article provides in-depth information about the development of the LIVESTRONG at the YMCA program and its subsequent spread to meet the physical activity needs of survivors across the country. Participating YMCAs engage in regular data collection efforts to track progress on organizational change and program delivery. These efforts include a staff evaluation survey, functional assessment of participants, patient-reported health status assessment, and patient program evaluation. From the time of its development, the LIVESTRONG at the YMCA program has served more than 29,000 survivors and trained more than 2,200 LIVESTRONG at the YMCA instructors. A national survey of more than 1,600 program participants demonstrates positive outcomes on health and well-being, as well as intent to continue exercising after the program's end.


Cognitive predictors of adolescent social anxiety.
Identifying psychological processes that maintain social anxiety holds promise for improving treatment outcomes for young people. Experimental and prospective studies in adults suggest negative social cognitions, safety behaviours, self-focused attention, and pre- and post-event processing are all implicated in the maintenance of social anxiety. Despite social anxiety typically starting in adolescence, prospective studies examining these cognitive processes in youth are lacking. The current study examined prospective associations between these five cognitive processes and social anxiety in a sample of 614 participants (53% girls; aged 11-14 years). Psychological processes, social anxiety symptoms, and depressive symptoms were assessed using self-report questionnaires at two time points. Negative social cognitions, safety behaviours, self-focused attention, and post-event processing predicted prospective levels of social anxiety over and above the effect of baseline levels of social anxiety. When these process variables were entered together in a regression model, three of them were independently associated with prospective social anxiety. Neither pre- nor post-event processing independently predicted later social anxiety over and above the effects of other psychological process variables. The findings indicate that these psychological processes are promising targets for treatment in adolescent social anxiety.


Duration of nuclear NF-kappaB action regulated by reversible acetylation.
The nuclear expression and action of the nuclear factor kappa B (NF-kappaB) transcription factor requires signal-coupled phosphorylation and degradation of the IkappaB inhibitors, which normally bind and sequester this pleiotropically active factor in the cytoplasm. The subsequent molecular events that regulate the termination of nuclear NF-kappaB action remain poorly defined, although the activation of de novo IkappaBalpha gene expression by NF-kappaB likely plays a key role. Our studies now demonstrate that the RelA subunit of NF-kappaB is subject to inducible acetylation and that acetylated forms of RelA interact weakly, if at all, with IkappaBalpha. Acetylated RelA is subsequently deacetylated through a specific interaction with histone deacetylase 3 (HDAC3). This deacetylation reaction promotes effective binding to IkappaBalpha and leads in turn to IkappaBalpha-dependent nuclear export of the complex through a chromosomal region maintenance-1 (CRM-1)-dependent pathway. Deacetylation of RelA by HDAC3 thus acts as an intranuclear molecular switch that both controls the duration of the NF-kappaB transcriptional response and contributes to the replenishment of the depleted cytoplasmic pool of latent NF-kappaB-IkappaBalpha complexes.


Successful kidney transplantation from a donation after cardiac death donor with an ileal conduit.
Kidney transplantation is the treatment of choice for those affected by end-stage renal disease. Consent for organ donation continues to be one of the greatest challenges to transplanting more patients waiting for a life-saving transplant. In an attempt to increase the donor pool for patients on kidney transplant waiting lists, transplant surgeons and physicians have expanded their acceptance criteria to include expanded criteria donors, donation after cardiac death donors, as well as those donors who present unique technical challenges to organ recovery. Here we report a successful kidney transplant from a kidney donor who died from cardiac causes and who previously underwent an ileal conduit for a neurogenic urinary bladder secondary to a spinal cord injury.


The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: a systematic review and meta-analysis.
Selective digestive decontamination (SDD) refers to the use of antimicrobials to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract to prevent infections caused by these organisms. Liver transplant patients are highly vulnerable to bacterial infection particularly with gram-negative organisms within the first month after transplantation, and SDD has been proposed as a potential measure to prevent these infections. However, the benefit of this procedure remains controversial. We undertook a systematic review and meta-analysis to determine whether SDD is beneficial in reducing infections overall and those caused by gram-negative bacteria in patients following liver transplantation. All studies that evaluated the efficacy of SDD in liver transplant patients were included. Randomized trials that included liver transplant patients given SDD versus either placebo or no treatment or minimal treatment (e.g., oral nystatin alone), and that provided adequate data to calculate a relative risk ratio, were included in the meta-analysis. Our review shows that most studies found SDD to be effective in reducing gram-negative infection. The nonrandomized and uncontrolled trials also showed benefit with SDD in reducing overall infection; however, the effect on overall infection was limited in the 4 randomized trials, in which the pooled relative risk was 0.88 (95% CI, 0.7-1.1), indicating no statistically significant reduction in infection with the use of SDD. The summary risk ratio for the association between SDD and gram-negative infection was 0.16 (95% CI, 0.07-0.37), indicating an 84% relative risk reduction in the incidence of infection caused by gram-negative bacteria in patients receiving SDD in randomized trials. In conclusion, the available literature supports a beneficial effect of SDD on gram-negative infection following liver transplantation; however, the risk of antimicrobial resistance must be considered. Larger multicenter randomized trials in this patient population to assess the effect of SDD in reducing infection and mortality, while assessing the risk of antimicrobial resistance, are needed.


Survival of knee arthroplasties. A nation-wide multicentre investigation of 8000 cases.
A prospective nation-wide study of knee arthroplasty has been under way in Sweden since October 1975. By the end of 1983, 4505 arthroplasties for osteoarthritis and 3495 for rheumatoid arthritis had been recorded and reviewed one, three and six years after the operation. Using actuarial methods, the probability of the prosthesis remaining in situ after six years was calculated. In osteoarthritis this probability ranged from 65% for hinged prostheses to 90% for medial compartment prostheses. Two-and three-compartment prostheses produced intermediate results with 87% survival. In rheumatoid arthritis the probability varied from 72% for medial compartment prostheses to 90% for two- and three-compartment prostheses. The main reason for failure was loosening of the components, the second most common was infection. The probability of revision for infection by six years was 2% in osteoarthritis and 3% in rheumatoid arthritis. Most revisions were to a three-compartment prosthesis. Knee fusion at primary revision was required in 2% of the cases at six years.


Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing.
Rapid diagnosis of drug-resistant tuberculosis (TB) is required for better patient management and treatment outcomes. Whole-genome sequencing (WGS) can be used to detect single nucleotide polymorphisms (SNPs) and deletions/insertions that are responsible for mostMycobacterium tuberculosis drug resistance. WGS is being performed at scale in high-income countries, but there are limited reports of its use in India. In this study, 33 clinicalM. tuberculosis isolates from the Mycobacterial Repository in Chandigarh underwent WGS. Phenotypic drug susceptibility testing was performed according to World Health Organization (WHO) recommendations. Four isolates were excluded from the analysis due to culture contamination or mislabelling during the study. Among the remaining 29 isolates, 21 (72.4%) were multidrug-resistant TB (MDR-TB) and 1 (3.4%) was extensively-drug resistant TB (XDR-TB). The most common mutations observed for isoniazid, rifampicin, ofloxacin and kanamycin resistance werekatG(S315T), rpoB(S450L), gyrA(A90V) and rrs(A1401G), respectively. The isolates mainly belonged to lineages 2 and 3, with most MDR-TB among lineage 2 isolates. WGS ofM. tuberculosis isolates allows the detection of drug resistance to all drugs in a single test and also provides insight into the evolution and drug-resistant TB.


Transcanal surgery for vestibular schwannomas: a pictorial review of radiological findings, surgical anatomy and comparison to the traditional translabyrinthine approach.
The most popular approaches for vestibular schwannoma (VS) removal are retrosigmoid, middle cranial fossa and translabyrinthine (TL). All require a certain degree of invasivity, bone removal, or brain manipulation. Recently, the authors described the transcanal transpromontorial approaches (TTA), which allow the inner ear to be accessed directly through the external auditory canal (EAC), either with a microscopic (Expanded TTA, or ExpTTA) or even an exclusive endoscopic technique (Endoscopic TTA, or EndoTTA). The advantages compared to traditional approaches are a direct view of the internal auditory canal (IAC) from lateral to medial, very little or no superficial tissue dissection and very little petrous bone drilling. In summary, from an anatomical point of view, they could be considered to be minimally invasive approaches. The radiologic outcome and the anatomical correspondence of these new approaches are described so as to share with the readers the possible radiologic findings and to compare and differentiate them from classic transpetrous approaches such as the TL approach. 4.


Computer-aided system of evaluation for population-based all-in-one service screening (CASE-PASS): from study design to outcome analysis with bias adjustment.
Population-based routine service screening has gained popularity following an era of randomized controlled trials. The evaluation of these service screening programs is subject to study design, data availability, and the precise data analysis for adjusting bias. We developed a computer-aided system that allows the evaluation of population-based service screening to unify these aspects and facilitate and guide the program assessor to efficiently perform an evaluation. This system underpins two experimental designs: the posttest-only non-equivalent design and the one-group pretest-posttest design and demonstrates the type of data required at both the population and individual levels. Three major analyses were developed that included a cumulative mortality analysis, survival analysis with lead-time adjustment, and self-selection bias adjustment. We used SAS AF software to develop a graphic interface system with a pull-down menu style. We demonstrate the application of this system with data obtained from a Swedish population-based service screen and a population-based randomized controlled trial for the screening of breast, colorectal, and prostate cancer, and one service screening program for cervical cancer with Pap smears. The system provided automated descriptive results based on the various sources of available data and cumulative mortality curves corresponding to the study designs. The comparison of cumulative survival between clinically and screen-detected cases without a lead-time adjustment are also demonstrated. The intention-to-treat and noncompliance analysis with self-selection bias adjustments are also shown to assess the effectiveness of the population-based service screening program. Model validation was composed of a comparison between our adjusted self-selection bias estimates and the empirical results on effectiveness reported in the literature. We demonstrate a computer-aided system allowing the evaluation of population-based service screening programs with an adjustment for self-selection and lead-time bias. This is achieved by providing a tutorial guide from the study design to the data analysis, with bias adjustment.


Reduced IL-37 Production Increases Spontaneous Chemokine Expressions in Colon Epithelial Cells.
Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhea. Previously, we showed enhanced chemokine productions in microscopic colitis patients, indicating dysregulated immune cell chemotaxis in the immunopathogenesis. We also showed decreased mRNA of IL-37, mainly regarded as an anti-inflammatory cytokine, in the colonic mucosa of these patients, potentially an important factor for the chronicity of the colitis. Our aim in this study was to understand the possible role of IL-37 in chemokine production using a cell line model. A colon epithelial cell line, T84, was stimulated with the TLR5 ligand flagellin. IL-37 protein production was reduced 20% using the CRISPR/Cas9 system, and the changes in chemokine mRNA and protein expressions were compared to cells transfected with empty plasmid. The 20% reduction in IL-37 protein levels spontaneously increased CCL5, CXCL8, CXCL10, and CXCL11 mRNA and protein expressions. CCL2 mRNA and protein levels were enhanced upon TLR5 stimulation. CCL3, CCL20, and CX3CL1 mRNA expressions were increased either spontaneously or following TLR5 stimulation, whereas CCL4 and CCL22 mRNA expressions were significantly decreased. Even a minor decrease in the ability of colon epithelial cells to produce IL-37 results in altered chemokine expression, mainly an increase in the production of several chemokines. Our results indicate that a decreased IL-37 expression by colon epithelial cells may be an important factor for increasing the recruitment of immune cells and subsequently developing microscopic colitis.


Laser calorimeter for UV absorption measurement of dielectric thin films.
We describe a dual-technique laser calorimeter for measuring the absorption of dielectric thin films in the UV region below 400 nm. The instrument measures the temperature rise and absorption of a sample simultaneously by two independent techniques, namely, a resistance thermometer and a temperature transducer. The absorption constant beta and extinction coefficient kappa of Sb(2)O(3) and ZrO(2) films at 308 and 337 nm are measured by using the calorimeter. The principle, construction, and application of the calorimeter are described.


Adherence to Diet and Physical Activity Cancer Prevention Guidelines and Cancer Outcomes: A Systematic Review.
Many studies have reported that adherence to health promotion guidelines for diet, physical activity, and maintenance of healthy body weight may decrease cancer incidence and mortality. A systematic review was performed to examine associations between adherence to established cancer prevention guidelines for diet and physical activity and overall cancer incidence and mortality. PubMed, Google Scholar, and Cochrane Reviews databases were searched following the current recommendations of Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA). Twelve studies met inclusion criteria for this review. High versus low adherence to established nutrition and physical activity cancer prevention guidelines was consistently and significantly associated with decreases of 10% to 61% in overall cancer incidence and mortality. Consistent significant reductions were also shown for breast cancer incidence (19%-60%), endometrial cancer incidence (23%-60%), and colorectal cancer incidence in both men and women (27%-52%). Findings for lung cancer incidence were equivocal, and no significant relationships were found between adherence and ovarian or prostate cancers. Adhering to cancer prevention guidelines for diet and physical activity is consistently associated with lower risks of overall cancer incidence and mortality, including for some site-specific cancers. Cancer Epidemiol Biomarkers Prev; 25(7); 1018-28. ©2016 AACR.


Versatile attosecond beamline in a two-foci configuration for simultaneous time-resolved measurements.
We present our attoline which is a versatile attosecond beamline at the Ultrafast Laser Physics Group at ETH Zurich for attosecond spectroscopy in a variety of targets. High-harmonic generation (HHG) in noble gases with an infrared (IR) driving field is employed to generate pulses in the extreme ultraviolet (XUV) spectral regime for XUV-IR cross-correlation measurements. The IR pulse driving the HHG and the pulse involved in the measurements are used in a non-collinear set-up that gives independent access to the different beams. Single attosecond pulses are generated with the polarization gating technique and temporally characterized with attosecond streaking. This attoline contains two target chambers that can be operated simultaneously. A toroidal mirror relay-images the focus from the first chamber into the second one. In the first interaction region a dedicated double-target allows for a simple change between photoelectron/photoion measurements with a time-of-flight spectrometer and transient absorption experiments. Any end station can occupy the second interaction chamber. A surface analysis chamber containing a hemispherical electron analyzer was employed to demonstrate successful operation. Simultaneous RABBITT measurements in two argon jets were recorded for this purpose.


Characterization of N-acylhomoserine lactone-degrading bacteria associated with the Zingiber officinale (ginger) rhizosphere: co-existence of quorum quenching and quorum sensing in Acinetobacter and Burkholderia.
Cell-to-cell communication (quorum sensing (QS)) co-ordinates bacterial behaviour at a population level. Consequently the behaviour of a natural multi-species community is likely to depend at least in part on co-existing QS and quorum quenching (QQ) activities. Here we sought to discover novel N-acylhomoserine lactone (AHL)-dependent QS and QQ strains by investigating a bacterial community associated with the rhizosphere of ginger (Zingiber officinale) growing in the Malaysian rainforest. By using a basal growth medium containing N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) as the sole source of carbon and nitrogen, the ginger rhizosphere associated bacteria were enriched for strains with AHL-degrading capabilities. Three isolates belonging to the genera Acinetobacter (GG2), Burkholderia (GG4) and Klebsiella (Se14) were identified and selected for further study. Strains GG2 and Se14 exhibited the broadest spectrum of AHL-degrading activities via lactonolysis while GG4 reduced 3-oxo-AHLs to the corresponding 3-hydroxy compounds. In GG2 and GG4, QQ was found to co-exist with AHL-dependent QS and GG2 was shown to inactivate both self-generated and exogenously supplied AHLs. GG2, GG4 and Se14 were each able to attenuate virulence factor production in both human and plant pathogens. Collectively our data show that ginger rhizosphere bacteria which make and degrade a wide range of AHLs are likely to play a collective role in determining the QS-dependent phenotype of a polymicrobial community.


WE-C-217BCD-03: Restricted Data Set Reconstruction Based on Respiration Quality to Improve Prospectively Gated in Vivo Micro-CT of Mice.
Micro-CT is commonly employed for lung imaging of mice; prospective gating allows for in-vivo imaging of free-breathing subjects. While this technique is successfully executed for healthy animals, results are less consistent for some disease models whose symptoms include irregular or unstable respiration. The purpose of this work is to repair the quality of high-blur images that arise from respiration instability using a retrospective method of motion reduction which identifies the individual x-ray projection images contributing most to the motion blur. Reconstructions were performed after the exclusion of these projections (the so-called restricted set). Sixteen mice were imaged using field emission cone beam micro-CT and prospective gating with a bellows-type respiration sensor. The scanner was operated in step-and-shoot mode; 400 projection images were acquired per scan. An algorithm was developed to analyze the respiration trace file and segment the individual breath corresponding to each projection image. We tested three different criteria to define a bad breath shape (correlation, mean breath height, or mode breath height), and restricted data set reconstructions were performed using each of these criteria to exclude projections corresponding to bad breaths. Each restricted set was compared against the full unrestricted data set image; the slope perpendicular to the diaphragm was used as a quantitative assessment of motion blur. All image sets saw a reduction in motion blur with at least one restriction technique. In 22 of 27 images, improvement was measured regardless of the removal criterion. Five percent total projection removal is optimal; a more aggressive correction increases the likelihood of under-sampling artifacts. Removing a subset of bad projections from otherwise complete image sets measurably decreases motion blur in respiratory-gated imaging. An approach based on breath height generally provides the best results. The technique is applicable to a variety of imaging modalities.


Mastery motivation and school readiness among young children experiencing homelessness.
Psychosocial risk exposure in childhood is associated with a greater probability of emotional, behavioral, and academic problems. It is not surprising that children who experience homelessness, a marker of high cumulative risk, show significant emotional and behavioral problems and lower academic achievement than other children, including impoverished children who are not homeless. Nonetheless, some children manifest positive adjustment despite the hazards associated with homelessness, and it is important to identify protective influences that might be targeted for intervention. One potential factor is mastery motivation (MM), or the drive to control and master challenges, theoretically associated with resilience and empirically linked to adaptive cognitive outcomes in low-risk children. Currently, there is little research on MM in high-risk young children overall, and data are particularly limited on the key question of whether MM is associated with better outcomes in domains crucial for school readiness, including socioemotional adjustment, self-regulation, and academic competence. This study examined observed MM in 85 young children ages 3 to 5 living with their parents in an emergency shelter. Children completed behavioral tasks to assess MM, and measures linked with school readiness were assessed directly or by parent report. Higher MM was associated with better social and emotional functioning and emotion regulation but not math achievement or executive functioning. Follow-up analyses indicated that MM was indirectly associated with prosocial behavior through better emotion-regulation abilities. Implications are discussed for further research and for interventions designed to address educational disparities and promote school success for children experiencing homelessness. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


The importance of fibroblasts in remodelling of the human uterine cervix during pregnancy and parturition.
It is well established that fibroblasts play a crucial role in pathophysiological extracellular matrix remodelling. The aim of this project is to elucidate their role in normal physiological remodelling. Specifically, the remodelling of the human cervix during pregnancy, resulting in an enabled passage of the child, is used as the model system. Fibroblast cultures were established from cervices of non-pregnant women, women after 36 weeks of pregnancy and women directly after partus. The cells were immunostained and quantified by western blots for differentiation markers. The cultures were screened for cytokine and metalloproteinase production and characterized by global proteome analysis. The cell cultures established from partal donors differ significantly from those from non-pregnant donors, which is in accordance with in vivo findings. A decrease in alpha-smooth actin and prolyl-4-hydroxylase and an increase in interleukin (IL)-6, IL-8 and matrix metalloproteinases (MMP)-1 and MMP-3 were observed in cultures from partal donors. 2D-gel electrophoresis followed by mass spectrometry showed that the expression of 59 proteins was changed significantly in cultures of partal donors. The regulated proteins are involved in protein kinase C signalling, Ca2+ binding, cytoskeletal organization, angiogenesis and degradation. Our data suggest that remodelling of the human cervix is orchestrated by fibroblasts, which are activated or recruited by the inflammatory processes occurring during the ripening cascade.


Phase stability, electronic structures and elastic properties of (U,Np)O2 and (Th,Np)O2 mixed oxides.
Mixing enthalpies (ΔHmix) of U1-xNpxO2 and Th1-xNpxO2 solid solutions are derived from atomic scale simulations based on density functional theory (DFT) employing the generalised gradient approximation corrected with an effective Hubbard parameter (Ueff). The variation of structural and electronic properties of UO2 and NpO2 with collinear ferromagnetic (FM), collinear anti-ferromagnetic (AFM) and non-collinear anti-ferromagnetic arrangements of the uranium and neptunium magnetic moments are investigated while ramping up Ueff from 0 eV to 4 eV (the Ueff-ramping method). A combination of the Ueff-ramping method to treat the presence of metastable magnetic states and special-quasirandom structures (SQS) for the random distribution of Np atoms in UO2 and ThO2 is employed to calculate ΔHmix of U1-xNpxO2 and Th1-xNpxO2 mixed oxides (MOX). The effect of collinear FM and AFM ordering is also considered in determining the ΔHmix. The calculated ΔHmix of Th1-xNpxO2 MOX were positive compared to the end members and nearly symmetric around x = 0.5 and ΔHmix of the AFM configuration were higher compared to the FM configuration maximum by 0.19 kJ mol-1. The ΔHmix of U1-xNpxO2 MOX were negative up to U0.50Np0.50O2 with a maximum value of -1.21 kJ mol-1 for U0.4375Np0.5625O2 whereas Np-rich (U,Np)O2 MOX compositions exhibited ΔHmix close to zero. Values of ΔHmix for (Th,Np)O2 are consistent with a simple miscibility-gap phase diagram while those for (U,Np)O2 suggest more complex behaviour. Nevertheless, lattice parameter variation with composition still follows a Vegard's law relationship. Finally, single crystal elastic constants of pure oxides and MOX are reported. The linear-elasticity models describe the mixing energies to within an accuracy of approximately 1 kJ mol-1 for the U1-xNpxO2 and Th1-xNpxO2 MOX systems.


The GPCOG: a new screening test for dementia designed for general practice.
To design and test a brief, efficient dementia-screening instrument for use by general practitioners (GPs). The General Practitioner Assessment of Cognition (GPCOG) consists of cognitive test items and historical questions asked of an informant. The validity of the measure was assessed by comparison with the criterion standard of diagnoses of dementia derived from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Primary care doctors' offices. Sixty-seven GPs administered the GPCOG to 283 community-dwelling patients aged 50 to 74 with memory complaints or aged 75 and older. The Cambridge Mental Disorder of the Elderly Examination, the Abbreviated Mental Test (AMT), the Mini-Mental State Examination (MMSE), the 15-item Geriatric Depression Scale, and the 12-item Short-Form Health Survey. The GPCOG was reliable and superior to the AMT (and possibly to the MMSE) in detecting dementia. The two-stage method of administering the GPCOG (cognitive testing followed by informant questions if necessary)had a sensitivity of 0.85, a specificity of 0.86, a misclassification rate of 14%, and positive predictive value of 71.4%. Patient interviews took less than 4 minutes to administer and informant interviews less than 2 minutes. The instrument was reported by GPs to be practical to administer and was acceptable to patients. The GPCOG is a valid, efficient, well-accepted instrument for dementia screening in primary care.


Primary headache disorders in the adult general population of Pakistan - a cross sectional nationwide prevalence survey.
The large geographical gaps in our knowledge of the prevalence and burden of headache disorders include almost all of Eastern Mediterranean Region (EMR). We report a nationwide population-based study in Pakistan, an EMR country with the sixth largest population in the world, conducted as a project within the Global Campaign against Headache. We surveyed six locations from the four provinces of Pakistan: Punjab, Sindh, Khyber Pakhtunkhwa and Baluchistan. We randomly selected and visited rural and urban households in each. One adult member (18-65 years) of each household, also randomly selected, was interviewed by a trained non-medical interviewer from the same location using a previously-validated structured questionnaire translated into Urdu, the national language. We estimated 1-year prevalences of the headache disorders of public-health importance and examined their associations with demographic variables using multivariate analysis. There were 4223 participants (mean age 34.4 ± 11.0 years; male 1957 [46.3%], female 2266 [53.7%]; urban 1443 [34.2%], rural 2780 [65.8%]). Participation proportion was 89.5%. Headache in the previous year was reported by 3233 (76.6% [95% CI: 75.3-77.8%]). The age- and gender-adjusted 1-year prevalence of migraine was 22.5% [21.2-23.8%] (male 18.0% [16.8-19.2%], female 26.9% [25.6-28.2%]), of tension-type headache (TTH) 44.6% [43.1-46.1%] (male 51.2% [49.7-52.7%], female 37.9% [36.4-39.4%]), of probable medication-overuse headache 0.7% [0.5-1.0%] (male 0.7% [0.5-1.0%], female 0.8% [0.5-1.1%]) and of other headache on ≥15 days/month 7.4% [6.6-8.2%] (male 4.4% [3.8-5.0%], female 10.4% [9.5-11.3%]). Migraine was more prevalent in females by a factor of 3:2 although this association barely survived (P = 0.039) after correcting for other factors. TTH was more prevalent in males by about 4:3 (P = 0.026). All headache and migraine were age-related, peaking in the age group 40-49 years; TTH peaked a decade earlier. Higher education (P = 0.004) and income (P = 0.001) were negatively associated with prevalence of migraine. With three quarters of its population affected, headache disorders must be on the public-health agenda of Pakistan. Worldwide, these disorders are the third leading cause of disability; information from specific enquiry into the burden attributable to headache disorders in this country is needed to inform health policy and priority-setting, and will be reported soon.


Large nearshore storm waves off the Irish coast.
We present a statistical analysis of nearshore waves observed during two major North-East Atlantic storms in 2015 and 2017. Surface elevations were measured with a 5-beam acoustic Doppler current profiler (ADCP) at relatively shallow waters off the west coast of Ireland. To compensate for the significant variability of both sea states in time, we consider a novel approach for analyzing the non-stationary surface-elevation series and compare the distributions of crest and wave heights observed with theoretical predictions based on the Forristall, Tayfun and Boccotti models. In particular, the latter two models have been largely applied to and validated for deep-water waves. We show here that they also describe well the characteristics of waves observed in relatively shallow waters. The largest nearshore waves observed during the two storms do not exceed the rogue thresholds as the Draupner, Andrea, Killard or El Faro rogue waves do in intermediate or deep-water depths. Nevertheless, our analysis reveals that modulational instabilities are ineffective, third-order resonances negligible and the largest waves observed here have characteristics quite similar to those displayed by rogue waves for which second order bound nonlinearities are the principal factor that enhances the linear dispersive focusing of extreme waves.


Low-dose propofol for the abortive treatment of pediatric migraine in the emergency department.
Limited progress has been made in the past decade for abortive treatment of migraine headache in the pediatric emergency department (PED). Propofol, a general anesthetic, has been reported to be effective in the treatment of refractory headaches in adults at subanesthetic doses but never in the pediatric population. The goal of this study was to review our institution's experience with subanesthetic doses of propofol for the abortive treatment of pediatric migraine and compare propofol with standard abortive therapy in the PED. Retrospective review of all patients discharged from the Oregon Health and Science University PED with a diagnosis of migraine headache from January 2010 to July 2011. Patients treated with subanesthetic doses of propofol were compared with matched controls who received standard abortive migraine therapy, defined as the combined use of a nonsteroidal anti-inflammatory medication, diphenhydramine, and prochlorperazine. Outcome variables of interest included reduction of pain as measured on a self-reported visual analog scale and length of stay after administration of initial abortive medication. Patients who received subanesthetic doses of propofol achieved significantly greater reduction in pain scores (80.1% vs 61.1%; P < 0.05) compared with matched controls as well as shorter stay (122 minutes vs 203 minutes; P = 0.2) after treatment. No adverse effects (hypotension, respiratory depression, or hypoxia) were recorded in either group. Propofol seems to be effective for the abortive treatment of pediatric migraine headache in the PED. Further prospective trials are warranted to either support or refute these initial findings.


Insights into the evolution and emergence of a novel infectious disease.
Many zoonotic, novel infectious diseases in humans appear as sporadic infections with spatially and temporally restricted outbreaks, as seen with influenza A(H5N1). Adaptation is often a key factor for successfully establishing sustained human-to-human transmission. Here we use simple mathematical models to describe different adaptation scenarios with particular reference to spatial heterogeneity within the human population. We present analytical expressions for the probability of emergence per introduction, as well as the waiting time to a successful emergence event. Furthermore, we derive general analytical results for the statistical properties of emergence events, including the probability distribution of outbreak sizes. We compare our analytical results with a stochastic model, which has previously been studied computationally. Our results suggest that, for typical connection strengths between communities, spatial heterogeneity has only a weak effect on outbreak size distributions, and on the risk of emergence per introduction. For example, if R₀ = 1.4 or larger, any village connected to a large city by just ten commuters a day is, effectively, just a part of the city when considering the chances of emergence and the outbreak size distribution. We present empirical data on commuting patterns and show that the vast majority of communities for which such data are available are at least this well interconnected. For plausible parameter ranges, the effects of spatial heterogeneity are likely to be dominated by the evolutionary biology of host adaptation. We conclude by discussing implications for surveillance and control of emerging infections.