Abstract: This paper proposes K-NRM, a kernel based neural model for document ranking. Given a query and a set of documents, K-NRM uses a translation matrix that models word-level similarities via word embeddings, a new kernel-pooling technique that uses kernels to extract multi-level soft match features, and a learning-to-rank layer that combines those features into the final ranking score. The whole model is trained end-to-end. The ranking layer learns desired feature patterns from the pairwise ranking loss. The kernels transfer the feature patterns into soft-match targets at each similarity level and enforce them on the translation matrix. The word embeddings are tuned accordingly so that they can produce the desired soft matches. Experiments on a commercial search engine's query log demonstrate the improvements of K-NRM over prior feature-based and neural-based states-of-the-art, and explain the source of K-NRM's advantage: Its kernel-guided embedding encodes a similarity metric tailored for matching query words to document words, and provides effective multi-level soft matches.

Abstract: One of the mysteries in the success of neural networks is randomly initialized first order methods like gradient descent can achieve zero training loss even though the objective function is non-convex and non-smooth. This paper demystifies this surprising phenomenon for two-layer fully connected ReLU activated neural networks. For an $m$ hidden node shallow neural network with ReLU activation and $n$ training data, we show as long as $m$ is large enough and no two inputs are parallel, randomly initialized gradient descent converges to a globally optimal solution at a linear convergence rate for the quadratic loss function. Our analysis relies on the following observation: over-parameterization and random initialization jointly restrict every weight vector to be close to its initialization for all iterations, which allows us to exploit a strong convexity-like property to show that gradient descent converges at a global linear rate to the global optimum. We believe these insights are also useful in analyzing deep models and other first order methods.

Abstract: Summary Background In the primary analysis of the NeoSphere trial, patients given neoadjuvant pertuzumab, trastuzumab, and docetaxel showed a significantly improved pathological complete response compared with those given trastuzumab and docetaxel after surgery. Here, we report 5-year progression-free survival, disease-free survival, and safety. Methods In this multicentre, open-label, phase 2 randomised trial in hospitals and medical clinics, treatment-naive adults with locally advanced, inflammatory, or early-stage HER2-positive breast cancer were randomly assigned (1:1:1:1) to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m 2 every 3 weeks, increasing to 100 mg/m 2 from cycle 2 if tolerated; group A), pertuzumab (840 mg loading dose, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B), pertuzumab and trastuzumab (group C), or pertuzumab and docetaxel (group D). After surgery, patients received three cycles of FEC (fluorouracil 600 mg/m 2 , epirubicin 90 mg/m 2 , and cyclophosphamide 600 mg/m 2 ) every 3 weeks (patients in group C received four cycles of docetaxel prior to FEC), and trastuzumab 6 mg/kg every 3 weeks to complete 1 year's treatment (17 cycles in total). Randomisation was done by a central centre using dynamic allocation, stratified by operable, locally advanced, and inflammatory breast cancer, and by oestrogen and/or progesterone receptor positivity. Safety analyses were done according to treatment received. The primary endpoint (pathological complete response) was previously reported; secondary endpoints reported here are 5-year progression-free survival (analysed in the intention-to-treat population) and disease-free survival (analysed in patients who had surgery). Secondary and exploratory analyses were not powered for formal statistical hypothesis testing, and therefore results are for descriptive purposes only. The study ended on Sept 22, 2014 (last patient, last visit). This study is registered with ClinicalTrials.gov, number NCT00545688. Findings Between Dec 17, 2007, and Dec 22, 2009, 417 eligible patients were randomly assigned to group A (107 patients), group B (107 patients), group C (107 patients), or group D (96 patients). One patient in group A withdrew before treatment. One patient assigned to group D received group A treatment, one patient assigned to group D received group B treatment, and one patient assigned to group B received group C treatment. At clinical cutoff, 87 patients had progressed or died. 5-year progression-free survival rates were 81% (95% CI 71–87) for group A, 86% (77–91) for group B, 73% (64–81) for group C, and 73% (63–81) for group D (hazard ratios 0·69 [95% CI 0·34–1·40] group B vs group A, 1·25 [0·68–2·30] group C vs group A, and 2·05 [1·07–3·93] group D vs group B). Disease-free survival results were consistent with progression-free survival results and were 81% (95% CI 72–88) for group A, 84% (72–91) for group B, 80% (70–86) for group C, and 75% (64–83) for group D. Patients who achieved total pathological complete response (all groups combined) had longer progression-free survival compared with patients who did not (85% [76–91] in patients who achieved total pathological response vs 76% [71–81] in patients who did not achieve total pathological response; hazard ratio 0·54 [95% CI 0·29–1·00]). There were no new or long-term safety concerns and tolerability was similar across groups (neoadjuvant and adjuvant treatment periods combined). The most common grade 3 or worse adverse events were neutropenia (group A: 71 [66%] of 107 patients; group B: 59 [55%] of 107; group C: 40 [37%] of 108; group D: 60 [64%] of 94), febrile neutropenia (group A: 10 [9%]; group B: 12 [11%]; group C: 5 [5%]; group D: 15 [16%]), and leucopenia (group A: 13 [12%]; group B: 6 [6%]; group C: 4 [4%]; group D: 8 [9%]). The number of patients with one or more serious adverse event was similar across groups (19–22 serious adverse events per group in 18–22% of patients). Interpretation Progression-free survival and disease-free survival at 5-year follow-up show large and overlapping CIs, but support the primary endpoint (pathological complete response) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that total pathological complete response could be an early indicator of long-term outcome in early-stage HER2-positive breast cancer. Funding F Hoffmann-La Roche.

Abstract: Importance Although concern exists regarding the rate of benzodiazepine use, especially long-term use by older adults, little information is available concerning patterns of benzodiazepine use in the United States. Objective To describe benzodiazepine prescription patterns in the United States focusing on patient age and duration of use. Design, Setting, and Participants A retrospective descriptive analysis of benzodiazepine prescriptions was performed with the 2008 LifeLink LRx Longitudinal Prescription database (IMS Health Inc), which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population. Main Outcomes and Measures The percentage of adults filling 1 or more benzodiazepine prescriptions during the study year by sex and age group (18-35 years, 36-50 years, 51-64 years, and 65-80 years) and among individuals receiving benzodiazepines, the corresponding percentages with long-term (≥120 days) benzodiazepine use, prescription of a long-acting benzodiazepine, and benzodiazepine prescriptions from a psychiatrist. Results In 2008, approximately 5.2% of US adults aged 18 to 80 years used benzodiazepines. The percentage who used benzodiazepines increased with age from 2.6% (18-35 years) to 5.4% (36-50 years) to 7.4% (51-64 years) to 8.7% (65-80 years). Benzodiazepine use was nearly twice as prevalent in women as men. The proportion of benzodiazepine use that was long term increased with age from 14.7% (18-35 years) to 31.4% (65-80 years), while the proportion that received a benzodiazepine prescription from a psychiatrist decreased with age from 15.0% (18-35 years) to 5.7% (65-80 years). In all age groups, roughly one-quarter of individuals receiving benzodiazepine involved long-acting benzodiazepine use. Conclusions and Relevance Despite cautions concerning risks associated with long-term benzodiazepine use, especially in older patients, long-term benzodiazepine use remains common in this age group. More vigorous clinical interventions supporting judicious benzodiazepine use may be needed to decrease rates of long-term benzodiazepine use in older adults.

Abstract: Background Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed i...

Abstract: We present UV, optical, and NIR photometry of the first electromagnetic counterpart to a gravitational wave source from Advanced LIGO/Virgo, the binary neutron star merger GW170817. Our data set extends from the discovery of the optical counterpart at $0.47$ days to $18.5$ days post-merger, and includes observations with the Dark Energy Camera (DECam), Gemini-South/FLAMINGOS-2 (GS/F2), and the {\it Hubble Space Telescope} ({\it HST}). The spectral energy distribution (SED) inferred from this photometry at $0.6$ days is well described by a blackbody model with $T\approx 8300$ K, a radius of $R\approx 4.5\times 10^{14}$ cm (corresponding to an expansion velocity of $v\approx 0.3c$), and a bolometric luminosity of $L_{\rm bol}\approx 5\times10^{41}$ erg s$^{-1}$. At $1.5$ days we find a multi-component SED across the optical and NIR, and subsequently we observe rapid fading in the UV and blue optical bands and significant reddening of the optical/NIR colors. Modeling the entire data set we find that models with heating from radioactive decay of $^{56}$Ni, or those with only a single component of opacity from $r$-process elements, fail to capture the rapid optical decline and red optical/NIR colors. Instead, models with two components consistent with lanthanide-poor and lanthanide-rich ejecta provide a good fit to the data, the resulting "blue" component has $M_\mathrm{ej}^\mathrm{blue}\approx 0.01$ M$_\odot$ and $v_\mathrm{ej}^\mathrm{blue}\approx 0.3$c, and the "red" component has $M_\mathrm{ej}^\mathrm{red}\approx 0.04$ M$_\odot$ and $v_\mathrm{ej}^\mathrm{red}\approx 0.1$c. These ejecta masses are broadly consistent with the estimated $r$-process production rate required to explain the Milky Way $r$-process abundances, providing the first evidence that BNS mergers can be a dominant site of $r$-process enrichment.

Abstract: Significance: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. Critical Issues: The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clin...

Abstract: Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.

Abstract: When experts are immersed in a task, do their brains prioritize task-related activity? Most efforts to understand neural activity during well-learned tasks focus on cognitive computations and task-related movements. We wondered whether task-performing animals explore a broader movement landscape and how this impacts neural activity. We characterized movements using video and other sensors and measured neural activity using widefield and two-photon imaging. Cortex-wide activity was dominated by movements, especially uninstructed movements not required for the task. Some uninstructed movements were aligned to trial events. Accounting for them revealed that neurons with similar trial-averaged activity often reflected utterly different combinations of cognitive and movement variables. Other movements occurred idiosyncratically, accounting for trial-by-trial fluctuations that are often considered 'noise'. This held true throughout task-learning and for extracellular Neuropixels recordings that included subcortical areas. Our observations argue that animals execute expert decisions while performing richly varied, uninstructed movements that profoundly shape neural activity.

Abstract: Background Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of

Abstract: Background There have been repeated calls to better involve patients and the public and to place them at the centre of healthcare. Serious clinical and service failings in the UK and internationally increase the urgency and importance of addressing this problem. Despite this supportive policy context, progress to achieve greater involvement is patchy and slow and often concentrated at the lowest levels of involvement. Methods A selective narrative literature search was guided by the authors’ broad expertise, covering a range of disciplines across health and social care, policy and research. Published systematic literature reviews were used to identify relevant authors and publications. Google and hand searches of journal articles and reference lists and reports augmented identification of recent evidence. Results Patients and the wider public can be involved at most stages of healthcare, and this can have a number of benefits. Uncertainty persists about why and how to do involvement well and evaluate its impact, how to involve and support a diversity of individuals, and in ways that allow them to work in partnership to genuinely influence decision-making. This exposes patient and public involvement (PPI) to criticisms of exclusivity and tokenism. Conclusions Current models of PPI are too narrow, and few organisations mention empowerment or address equality and diversity in their involvement strategies. These aspects of involvement should receive greater attention, as well as the adoption of models and frameworks that enable power and decision-making to be shared more equitably with patients and the public in designing, planning and co-producing healthcare.

Abstract: Annotating videos is cumbersome, expensive and not scalable. Yet, many strong video models still rely on manually annotated data. With the recent introduction of the HowTo100M dataset, narrated videos now offer the possibility of learning video representations without manual supervision. In this work we propose a new learning approach, MIL-NCE, capable of addressing mis- alignments inherent in narrated videos. With this approach we are able to learn strong video representations from scratch, without the need for any manual annotation. We evaluate our representations on a wide range of four downstream tasks over eight datasets: action recognition (HMDB-51, UCF-101, Kinetics-700), text-to- video retrieval (YouCook2, MSR-VTT), action localization (YouTube-8M Segments, CrossTask) and action segmentation (COIN). Our method outperforms all published self-supervised approaches for these tasks as well as several fully supervised baselines.

Abstract: In intelligent reflecting surface (IRS) assisted communication systems, the acquisition of channel state information is a crucial impediment for achieving the beamforming gain of IRS because of the considerable overhead required for channel estimation Specifically, under the current beamforming design for IRS-assisted communications, in total $KMN+KM$ channel coefficients should be estimated, where $K$ , $N$ and $M$ denote the numbers of users, IRS reflecting elements, and antennas at the base station (BS), respectively For the first time in the literature, this paper points out that despite the vast number of channel coefficients that should be estimated, significant redundancy exists in the user-IRS-BS reflected channels of different users arising from the fact that each IRS element reflects the signals from all the users to the BS via the same channel To utilize this redundancy for reducing the channel estimation time, we propose a novel three-phase pilot-based channel estimation framework for IRS-assisted uplink multiuser communications, in which the user-BS direct channels and the user-IRS-BS reflected channels of a typical user are estimated in Phase I and Phase II, respectively, while the user-IRS-BS reflected channels of the other users are estimated with low overhead in Phase III via leveraging their strong correlation with those of the typical user Under this framework, we analytically prove that a time duration consisting of $K+N+\max (K-1,\lceil (K-1)N/M \rceil)$ pilot symbols is sufficient for perfectly recovering all the $KMN+KM$ channel coefficients under the case without receiver noise at the BS Further, under the case with receiver noise, the user pilot sequences, IRS reflecting coefficients, and BS linear minimum mean-squared error channel estimators are characterized in closed-form

Abstract: Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.

Abstract: Intercellular communication was long thought to be regulated exclusively through direct contact between cells or via release of soluble molecules that transmit the signal by binding to a suitable receptor on the target cell, and/or via uptake into that cell. With the discovery of small secreted vesicular structures that contain complex cargo, both in their lumen and the lipid membrane that surrounds them, a new frontier of signal transduction was discovered. These “extracellular vesicles” (EV) were initially thought to be garbage bags through which the cell ejected its waste. Whilst this is a major function of one type of EV, i.e., apoptotic bodies, many EVs have intricate functions in intercellular communication and compound exchange; although their physiological roles are still ill-defined. Additionally, it is now becoming increasingly clear that EVs mediate disease progression and therefore studying EVs has ignited significant interests among researchers from various fields of life sciences. Consequently, the research effort into the pathogenic roles of EVs is significantly higher even though their protective roles are not well established. The “Focus on extracellular vesicles” series of reviews highlights the current state of the art regarding various topics in EV research, whilst this review serves as an introductory overview of EVs, their biogenesis and molecular composition.

Abstract: Quantum key distribution (QKD) systems often rely on polarization of light for encoding, thus limiting the amount of information that can be sent per photon and placing tight bounds on the error rates that such a system can tolerate. Here we describe a proof-of-principle experiment that indicates the feasibility of high-dimensional QKD based on the transverse structure of the light field allowing for the transfer of more than 1 bit per photon. Our implementation uses the orbital angular momentum (OAM) of photons and the corresponding mutually unbiased basis of angular position (ANG). Our experiment uses a digital micro-mirror device for the rapid generation of OAM and ANG modes at 4 kHz, and a mode sorter capable of sorting single photons based on their OAM and ANG content with a separation efficiency of 93%. Through the use of a seven-dimensional alphabet encoded in the OAM and ANG bases, we achieve a channel capacity of 2.05 bits per sifted photon. Our experiment demonstrates that, in addition to having an increased information capacity, multilevel QKD systems based on spatial-mode encoding can be more resilient against intercept-resend eavesdropping attacks.

Abstract: Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD.

Abstract: Superhydrophobic surfaces have received rapidly increasing research interest since the late 1990s because of their tremendous application potential in areas such as self-cleaning and anti-icing surfaces, drag reduction, and enhanced heat transfer ( 1 – 3 ). A surface is considered superhydrophobic if a water droplet beads up (with contact angles >150°), and moreover, if the droplet can slide away from the surface readily (i.e., it has small contact angle hysteresis). Two essential features are generally required for superhydrophobicity: a micro- or nanostructured surface texture and a nonpolar surface chemistry, to help trap a thin air layer that reduces attractive interactions between the solid surface and the liquid ( 4 , 5 ). However, such surface textures are highly susceptible to mechanical wear, and abrasion may also alter surface chemistry. Both processes can lead to loss of liquid repellency, which makes mechanical durability a central concern for practical applications ( 6 , 7 ). Identifying the most promising avenues to mechanically robust superhydrophobic materials calls for standardized characterization methods.

Abstract: Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.

Abstract: We show that the Graph Isomorphism (GI) problem and the related problems of String Isomorphism (under group action) (SI) and Coset Intersection (CI) can be solved in quasipolynomial (exp (logn) O(1) � ) time. The best previous bound for GI was exp(O( √ nlogn)), where n is the number of vertices (Luks, 1983); for the other two problems, the bound was similar, exp( e O( √ n)), where n is the size of the permutation domain (Babai, 1983). The algorithm builds on Luks’s SI framework and attacks the barrier configurations for Luks’s algorithm by group theoretic “local certificates” and combinatorial canonical partitioning techniques. We show that in a well-defined sense, Johnson graphs are the only obstructions to effective canonical partitioning.

Abstract: We predict enormous, anisotropic piezoelectric effects in intrinsic monolayer group IV monochalcogenides (MX, M=Sn or Ge, X=Se or S), including SnSe, SnS, GeSe, and GeS. Using first-principle simulations based on the modern theory of polarization, we find that their piezoelectric coefficients are about one to two orders of magnitude larger than those of other 2D materials, such as MoS2 and GaSe, and bulk quartz and AlN which are widely used in industry. This enhancement is a result of the unique “puckered” C2v symmetry and electronic structure of monolayer group IV monochalcogenides. Given the achieved experimental advances in the fabrication of monolayers, their flexible character, and ability to withstand enormous strain, these 2D structures with giant piezoelectric effects may be promising for a broad range of applications such as nano-sized sensors, piezotronics, and energy harvesting in portable electronic devices.

Abstract: We present a novel latent embedding model for learning a compatibility function between image and class embeddings, in the context of zero-shot classification. The proposed method augments the state-of-the-art bilinear compatibility model by incorporating latent variables. Instead of learning a single bilinear map, it learns a collection of maps with the selection, of which map to use, being a latent variable for the current image-class pair. We train the model with a ranking based objective function which penalizes incorrect rankings of the true class for a given image. We empirically demonstrate that our model improves the state-of-the-art for various class embeddings consistently on three challenging publicly available datasets for the zero-shot setting. Moreover, our method leads to visually highly interpretable results with clear clusters of different fine-grained object properties that correspond to different latent variable maps.

Abstract: This study compares the experiences of students in face-to-face (in class) discussions with threaded discussions and also evaluates the threaded discussions for evidence of higher-order thinking. Students were enrolled in graduate-level classes that used both modes (face-to-face and online) for course-related discussions; their end-of-course evaluations of both experiences were grouped for analysis and themes constructed based on their comments. Themes included the “expansion of time,” “experience of time,” “quality of the discussion,” “needs of the student,” and “faculty expertise.” While there are advantages to holding discussions in either setting, students most frequently noted that using threaded discussions increased the amount of time they spent on class objectives and that they appreciated the extra time for reflection on course issues. The face-to-face format also had value as a result of its immediacy and energy, and some students found one mode a better “fit” with their preferred learning mode. The analysis of higher-order thinking was based on a content analysis of the threaded discussions only. Each posting was coded as one of the four cognitive-processing categories described by Garrison and colleagues [1]: 18% were triggering questions, 51% were exploration, 22% were integration, and 7% resolution. A fifth category – social – was appropriate for 3% of the responses and only 12% of the postings included a writing error. This framework provides some support for the assertion that higher-order thinking can and does occur in online discussions; strategies for increasing the number of responses in the integration and resolution categories are discussed.

Abstract: We use 26×106 galaxies from the Dark Energy Survey (DES) Year 1 shape catalogs over 1321 deg2 of the sky to produce the most significant measurement of cosmic shear in a galaxy survey to date. We constrain cosmological parameters in both the flat ΛCDM and the wCDM models, while also varying the neutrino mass density. These results are shown to be robust using two independent shape catalogs, two independent photo-z calibration methods, and two independent analysis pipelines in a blind analysis. We find a 3.5% fractional uncertainty on σ8(Ωm/0.3)0.5=0.782-0.027+0.027 at 68% C.L., which is a factor of 2.5 improvement over the fractional constraining power of our DES Science Verification results. In wCDM, we find a 4.8% fractional uncertainty on σ8(Ωm/0.3)0.5=0.777-0.038+0.036 and a dark energy equation-of-state w=-0.95-0.39+0.33. We find results that are consistent with previous cosmic shear constraints in σ8—Ωm, and we see no evidence for disagreement of our weak lensing data with data from the cosmic microwave background. Finally, we find no evidence preferring a wCDM model allowing w≠-1. We expect further significant improvements with subsequent years of DES data, which will more than triple the sky coverage of our shape catalogs and double the effective integrated exposure time per galaxy.

Abstract: BackgroundThymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. MethodsWe compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednison...

Abstract: This article provides researchers with knowledge of how to design a high quality mixed methods research study. To design a mixed study, researchers must understand and carefully consider each of the dimensions of mixed methods design, and always keep an eye on the issue of validity. We explain the seven major design dimensions: purpose, theoretical drive, timing (simultaneity and dependency), point of integration, typological versus interactive design approaches, planned versus emergent design, and design complexity. There also are multiple secondary dimensions that need to be considered during the design process. We explain ten secondary dimensions of design to be considered for each research study. We also provide two case studies showing how the mixed designs were constructed.

Abstract: Background Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking. Methods Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics. Results The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed. Conclusions PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.