The effect of local wind on seismic noise near 1 Hz at the MELT site and in Iceland

The mantle electromagnetic and tomography (MELT) experiment on the east Pacific rise near 17°S was the first large teleseismic experiment on a midocean ridge. During the six-month deployment, no compressional arrivals were well recorded above 0.5 Hz. In comparison, the ICEMELT experiment in Iceland recorded compressional arrivals at 1-2 Hz from about 2 earthquakes per month. We compare noise spectra from the two experiments and show that this difference in detection is at least in part a result of noise. Near 1 Hz, seismic noise in the oceans is produced locally by wind-generated waves. At both experiment sites, 1-Hz noise levels are well correlated with local sea-surface-wind speeds derived from satellite observations. For a given wind speed, 1-Hz noise levels are about 10-20 dB lower in Iceland. At the MELT site, cross-correlations of wind speed with the logarithm of noise in a narrow-frequency band yield correlation coefficients exceeding 0.7 at frequencies between 0.4 Hz and 2 Hz. Noise levels at 1 Hz increase with wind by 1.3-1.4 dB per m/sec for wind speeds less than 10 m/sec. For the ICEMELT experiment, high correlation coefficients extend to markedly higher frequencies for coastal stations, and there is a 10-dB drop in 1-Hz noise levels 100-km inland. Noise levels increase by about 0.8 dB per m/sec. The strong correlation between wind speed and l-Hz seismic noise provides justification for using satellite wind speed data to search for locations on the global spreading system where there is a better probability of recording high-frequency arrivals. The calmest sites are found on the northern east Pacific rise, near the equator in all oceans, and near 34 ° N and 22 ° S on the mid- Atlantic ridge.This study was supported by the National Science Foundation under grant OCE-9414299.Peer Reviewe

Improving Requirements-Test Alignment by Prescribing Practices that Mitigate Communication Gaps

The communication of requirements within software development is vital for project success. Requirements engineering and testing are two processes that when aligned can enable the discovery of issues and misunderstandings earlier, rather than later, and avoid costly and time-consuming rework and delays. There are a number of practices that support requirements-test alignment. However, each organisation and project is different and there is no one-fits-all set of practices. The software process improvement method called Gap Finder is designed to increase requirements-test alignment. The method contains two parts: an assessment part and a prescriptive part. It detects potential communication gaps between people and between artefacts (the assessment part), and identifies practices for mitigating these gaps (the prescriptive part). This paper presents the design and formative evaluation of the prescriptive part; an evaluation of the assessment part was published previously. The Gap Finder method was constructed using a design science research approach and is built on the Theory of Distances for Software Engineering, which in turn is grounded in empirical evidence from five case companies. The formative evaluation was performed through a case study in which Gap Finder was applied to an on-going development project. A qualitative and mixed-method approach was taken in the evaluation, including ethnographically-informed observations. The results show that Gap Finder can detect relevant communication gaps and seven of the nine prescribed practices were deemed practically relevant for mitigating these gaps. The project team found the method to be useful and supported joint reflection and improvement of their requirements communication. Our findings demonstrate that an empirically-based theory can be used to improve software development practices and provide a foundation for further research on factors that affect requirements communicatio

Transepithelial Transport and Enzymatic Detoxification of Gluten in Gluten-Sensitive Rhesus Macaques

In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to the human condition of gluten sensitivity, celiac disease. This animal model of gluten sensitivity may therefore be useful toward studying both the pathogenesis and the treatment of celiac disease. Here, we perform two pilot experiments to demonstrate the potential utility of this model for studying intestinal permeability toward an immunotoxic gluten peptide and pharmacological detoxification of gluten in vivo by an oral enzyme drug candidate.Intestinal permeability was investigated in age-matched gluten-sensitive and control macaques by using mass spectrometry to detect and quantify an orally dosed, isotope labeled 33-mer gluten peptide delivered across the intestinal epithelium to the plasma. The protective effect of a therapeutically promising oral protease, EP-B2, was evaluated in a gluten-sensitive macaque by administering a daily gluten challenge with or without EP-B2 supplementation. ELISA-based antibody assays and blinded clinical evaluations of this macaque and of an age-matched control were conducted to assess responses to gluten.Labeled 33-mer peptide was detected in the plasma of a gluten-sensitive macaque, both in remission and during active disease, but not in the plasma of healthy controls. Administration of EP-B2, but not vehicle, prevented clinical relapse in response to a dietary gluten challenge. Unexpectedly, a marked increase in anti-gliadin (IgG and IgA) and anti-transglutaminase (IgG) antibodies was observed during the EP-B2 treatment phase.Gluten-sensitive rhesus macaques may be an attractive resource for investigating important aspects of celiac disease, including enhanced intestinal permeability and pharmacology of oral enzyme drug candidates. Orally dosed EP-B2 exerts a protective effect against ingested gluten. Limited data suggest that enhanced permeability of short gluten peptides generated by gastrically active glutenases may trigger an elevated antibody response, but that these antibodies are not necessarily causative of clinical illness

The Associations Between Children's and Adolescents’ Suicidal and Self-Harming Behaviors, and Related Behaviors Within Their Social Networks: A Systematic Review

© 2017, Copyright © International Academy for Suicide Research.Social influences—including the suicidal and self-harming behaviors of others—have been highlighted as a risk factor for suicidal and self-harming behavior in young people, but synthesis of the evidence is lacking. A systematic review of 86 relevant papers was conducted. Considerable published evidence was obtained for positive associations between young people's suicidal and self-harming behavior and that of people they know, with those reporting knowing people who had engaged in suicidal or self-harming behaviors more likely to report engaging in similar behaviors themselves. Findings are discussed in relation to a number of methodological and measurement issues—including the role of normative perceptions—and implications for the prevention of suicidal and self-harming behavior are considered

Pubertal development and risk of premenstrual disorders in young adulthood

STUDY QUESTION: Is pubertal timing associated with risk of premenstrual disorders (PMDs) in young adulthood? SUMMARY ANSWER: Late pubertal development is associated with decreased premenstrual symptom burden and risk of PMDs in young adulthood. WHAT IS KNOWN ALREADY: PMDs, including premenstrual syndrome and premenstrual dysphoric disorder, may begin during the teenage years. Few risk factors in early life have been identified for PMD development. STUDY DESIGN, SIZE, DURATION: A prospective cohort study of 6495 female participants during 1996-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included participants from the Growing Up Today Study (GUTS). Pubertal development was indicated by the timing of menarche, breast and pubic hair growth. Self-reported age at menarche was longitudinally assessed at enrollment (in 1996/2004 for GUTS I/II) and onwards, and classified as early (age ≤ mean - SD, 11.64 years), normative and late menarche (age ≥ mean + SD, 13.95 years). Timing of pubic hair and breast growth were assessed multiple times during follow-up via Tanner scales, and classified into early, normative and late development according to mean ± SD. Using a validated questionnaire based on the Calendar of Premenstrual Experiences, we assessed premenstrual symptoms and identified probable cases of PMDs in 2013. We examined the associations of timing of pubertal development with premenstrual symptom score and disorders using multivariable linear and logistic regressions, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In 2013 (mean age = 26), 1001 (15.4%) individuals met criteria for a PMD. An inverse association was found between age at menarche and premenstrual symptom z-score (β -0.05 per year, 95% CI -0.07 to -0.0

Synchronous Versus Metachronous Metastatic Disease: Impact of Time to Metastasis on Patient Outcome-Results from the International Metastatic Renal Cell Carcinoma Database Consortium

BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) may present with primary metastases (synchronous disease) or develop metastases during follow-up (metachronous disease). The impact of time to metastasis on patient outcome is poorly characterised. OBJECTIVE: To characterise overall survival (OS) and time to treatment failure (TTF) based on time to metastasis in mRCC patients treated with targeted therapy (tyrosine kinase inhibitors [TKIs]). DESIGN, SETTING, AND PARTICIPANTS: We used the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare synchronous (metastases within ≤3 mo of initial diagnosis of cancer) versus metachronous disease (evaluated by >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr intervals). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS and TFF were assessed using Kaplan-Meier curves. Cox multivariable regressions analyses (MVAs) were adjusted for baseline factors. RESULTS AND LIMITATIONS: Of 7386 patients with mRCC treated with first-line TKIs, 3906 (53%) and 3480 (47%) had synchronous and metachronous metastasis, respectively. More patients with synchronous versus metachronous disease had higher T stage (T1-2: 19% vs 34%), N1 disease (21% vs 6%), presence of sarcomatoid differentiation (15.8% vs 7.9%), Karnofsky performance status <80 (25.9% vs 15.1%), anaemia (62.5% vs 42.3%), elevated neutrophils (18.9% vs 10.9%), elevated platelets (21.6% vs 11.4%), bone metastases (40.4% vs 29.8%), and IMDC poor risk (40.6% vs 11.3%). Synchronous versus metachronous disease by intervals >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr correlated with poor TTF (5.6 mo vs 7.3, 8.0, 10.8, and 13.3 mo, p <  0.0001) and poor OS (median 16.7 mo vs 23.8, 30.2, 34.8, and 41.7 mo, p <  0.0001). In MVAs, the adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.98 (0.90-1.06), 0.81 (0.73-0.91), 0.74 (0.68-0.81), and 0.60 (0.54-0.67), respectively, for OS (p <  0.0001), and 1.00 (reference), 0.99 (0.92-1.06), 0.98 (0.90-1.07), 0.83 (0.77-0.89), and 0.66 (0.60-0.72), respectively, for TTF (p <  0.0001). Data were collected retrospectively. CONCLUSIONS: Timing of metastases after initial RCC diagnosis may impact the outcomes from targeted therapy in mRCC. PATIENT SUMMARY: We looked at the impact of the timing of metastatic outbreak on survival outcomes in kidney cancer patients treated with targeted therapy. We found that the longer time to metastatic development was associated with improved outcome

Evaluation of Clear Cell, Papillary, and Chromophobe Renal Cell Carcinoma Metastasis Sites and Association with Survival

Importance: There exists considerable biological and clinical variability between histologic variants of metastatic renal cell carcinoma (mRCC). Data reporting on patterns of metastasis in histologic variants of mRCC are sparse. Objective: To characterize sites of metastasis and their association with survival across the 3 most common histologic variants of mRCC: clear cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC). Design, Setting, and Participants: In this multicenter, international cohort study, the International mRCC Database Consortium (IMDC) database was used to identify consecutive patients starting systemic therapy for mRCC between 2002 and 2019. Patients with mixed histologic subtype were excluded. Statistical analysis was performed from February to June 2020. Exposures: Data regarding histologic subtype and sites of metastatic involvement at the time of first systemic therapy initiation were collected. Main Outcomes and Measures: The primary outcomes were prevalence of metastatic site involvement and overall survival (OS) from time of systemic therapy initiation. Patients with multiple sites of metastatic involvement were included in analyses of all groups to which they had metastases. Results: A total of 10105 patients were eligible for analysis. Median (interquartile range) age at diagnosis was 60 (53-67) years, 7310 (72.4%) were men and 8526 (84.5%) underwent nephrectomy. Of these, 9252 (92%) had ccRCC, 667 (7%) had pRCC, and 186 (2%) had chrRCC. The median number of sites of metastasis was 2 (range, 0-7). In ccRCC, the most common sites of metastasis were lung (70%; 6189 of 8804 patients [448 missing]), lymph nodes (45%; 3874 of 8655 patients [597 missing]), bone (32%; 2847 of 8817 patients [435 missing]), liver (18%; 1560 of 8804 [448 missing]), and adrenal gland (10%; 678 of 6673 patients [2579 missing]). Sites of metastasis varied between subtypes. Lung, adrenal, brain, and pancreatic metastases were more frequent in ccRCC, lymph node involvement was more common in pRCC, and liver metastases were more frequent in chrRCC. Median OS for ccRCC varied by site of metastatic involvement, ranging between 16 months (95% CI, 13.7-18.8 months) for the pleura and 50 months (95% CI, 41.1-55.5 months) for the pancreas. Compared with ccRCC, patients with pRCC tended to have lower OS, regardless of metastatic site. Conclusions and Relevance: Sites of metastatic involvement differ according to histologic subtype in mRCC and are associated with OS. These data highlight the clinical and biological variability between histologic subtypes of mRCC. Patterns of metastatic spread may reflect differences in underlying disease biology. Further work to investigate differences in immune, molecular, and genetic profiles between metastatic sites and histologic subtypes is encouraged

The effect of postexercise carbohydrate and protein ingestion on bone metabolism

Purpose To investigate the effect of feeding carbohydrate and protein (CHO+PRO), immediately or 2 h after an exhaustive run, on the bone turnover response in endurance runners. Methods 10 men (age 28±5 y, height 1.74±0.05 m, body mass 69.7±6.3 kg) performed treadmill running at 75%VO2max, until exhaustion, on three occasions. Blood was collected before and immediately, 1, 2, 3, 4 and 24 h post-exercise, for measurement of β-CTX, P1NP, PTH, PO4, ACa and Ca2+. This was a randomised, counterbalanced, placebo-controlled, single-blinded, cross-over study. The three trials were; i) placebo (PLA), PLA solution was ingested immediately and 2 h post-exercise, ii) immediate feeding (IF), CHO+PRO (1.5 g.kgBM-1 dextrose and 0.5 g.kgBM-1 whey) were ingested immediately post-exercise and PLA 2 h post-exercise, and iii) delayed feeding (DF), PLA was ingested immediately post-exercise and CHO+PRO solution 2 h post-exercise. Data were analysed using repeated measures ANOVA and post-hoc Tukey’s HSD. Results At 1 and 2 h post-exercise, β-CTX concentrations were lower in the IF trial than the DF and PLA trials (P≤0.001). At 3 h post-exercise, β-CTX concentrations were higher in the PLA trial than the IF (P≤0.001) and DF trials (P=0.026). At 4 h post-exercise, β-CTX concentrations were lower in the DF trial than the IF (P=0.003) and PLA trials (P≤0.001). At 4 h post-exercise, P1NP was higher in the IF trial than in DF (P=0.026) and PLA trials (P=0.001). At 3 h post-exercise, PTH was higher in the IF trial than the DF trial (P≤0.001). Conclusions Following exhaustive running, immediate ingestion of CHO+PRO may be beneficial, as it decreases bone resorption marker concentrations and increases bone formation marker concentrations; creating a more positive bone turnover balance