The covariance of cosmic shear correlation functions and cosmological parameter estimates using redshift information

Cosmological weak lensing by the large scale structure of the Universe, cosmic shear, is coming of age as a powerful probe of the parameters describing the cosmological model and matter power spectrum. It complements CMB studies, by breaking degeneracies and providing a cross-check. An important measure of the cosmic shear signal are the shear correlation functions; these can be directly calculated from data, and compared with theoretical expectations for different cosmological models and matter power spectra. We present a Monte Carlo method to quickly simulate mock cosmic shear surveys. One application of this method is in the determination of the full covariance matrix for the correlation functions; this includes redshift binning and is applicable to arbitrary survey geometries. Terms arising from shot noise and cosmic variance (dominant on small and large scales respectively) are accounted for naturally. As an illustration of the use of such covariance matrices, we consider to what degree confidence regions on parameters are tightened when redshift binning is employed. The parameters considered are those commonly discussed in cosmic shear analyses - the matter density parameter, dark energy density parameter (classical cosmological constant), power spectrum normalisation and shape parameter. We incorporate our covariance matrices into a likelihood treatment, and also use the Fisher formalism to explore a larger region of parameter space (abridged).Comment: 14 pages, 8 figures, accepted by A&A corrected typos, some changes in the discussion, shortened sections 2.1, 2.2 and 6.2.

A Catalog of Chandra X-ray Sources in the Carina Nebula

We present a catalog of ~14,000 X-ray sources observed by the ACIS instrument on the Chandra X-ray Observatory within a 1.42 square degree survey of the Great Nebula in Carina, known as the Chandra Carina Complex Project (CCCP). This study appears in a Special Issue of the ApJS devoted to the CCCP. Here, we describe the data reduction and analysis procedures performed on the X-ray observations, including calibration and cleaning of the X-ray event data, point source detection, and source extraction. The catalog appears to be complete across most of the field to an absorption-corrected total-band luminosity of ~10^{30.7} erg/s for a typical low-mass pre-main sequence star. Counterparts to the X-ray sources are identified in a variety of visual, near-infrared, and mid-infrared surveys. The X-ray and infrared source properties presented here form the basis of many CCCP studies of the young stellar populations in Carina.Comment: Accepted for the ApJS Special Issue on the Chandra Carina Complex Project (CCCP), scheduled for publication in May 2011. All 16 CCCP Special Issue papers are available at http://cochise.astro.psu.edu/Carina_public/special_issue.html through 2011 at least. 29 pages, 11 figure

Negative DNA supercoiling induces genome-wide Cas9 off-target activity

CRISPR-Cas9 is a powerful gene-editing technology; however, off-target activity remains an important consideration for therapeutic applications. We have previously shown that force-stretching DNA induces off-target activity and hypothesized that distortions of the DNA topology in vivo, such as negative DNA supercoiling, could reduce Cas9 specificity. Using single-molecule optical-tweezers, we demonstrate that negative supercoiling λ-DNA induces sequence-specific Cas9 off-target binding at multiple sites, even at low forces. Using an adapted CIRCLE-seq approach, we detect over 10,000 negative-supercoiling-induced Cas9 off-target double-strand breaks genome-wide caused by increased mismatch tolerance. We further demonstrate in vivo that directed local DNA distortion increases off-target activity in cells and that induced off-target events can be detected during Cas9 genome editing. These data demonstrate that Cas9 off-target activity is regulated by DNA topology in vitro and in vivo, suggesting that cellular processes, such as transcription and replication, could induce off-target activity at previously overlooked sites

Online and social networking interventions for the treatment of depression in young people: a systematic review

BACKGROUND: Major depression accounts for the greatest burden of all diseases globally. The peak onset of depression occurs between adolescence and young adulthood, and for many individuals, depression displays a relapse-remitting and increasingly severe course. Given this, the development of cost-effective, acceptable, and population-focused interventions for depression is critical. A number of online interventions (both prevention and acute phase) have been tested in young people with promising results. As these interventions differ in content, clinician input, and modality, it is important to identify key features (or unhelpful functions) associated with treatment outcomes. OBJECTIVE: A systematic review of the research literature was undertaken. The review was designed to focus on two aspects of online intervention: (1) standard approaches evaluating online intervention content in randomized controlled designs (Section 1), and (2) second-generation online interventions and services using social networking (eg, social networking sites and online support groups) in any type of research design (Section 2). METHODS: Two specific literature searches were undertaken. There was no date range specified. The Section 1 search, which focused on randomized controlled trials, included only young people (12-25 years) and yielded 101 study abstracts, of which 15 met the review inclusion criteria. The Section 2 search, which included all study design types and was not restricted in terms of age, yielded 358 abstracts, of which 22 studies met the inclusion criteria. Information about the studies and their findings were extracted and tabulated for review. RESULTS: The 15 studies identified in Section 1 described 10 trials testing eight different online interventions, all of which were based on a cognitive behavioral framework. All but one of the eight identified studies reported positive results; however, only five of the 15 studies used blinded interviewer administered outcomes with most trials using self-report data. Studies varied significantly in presentation of intervention content, treatment dose, and dropout. Only two studies included moderator or clinician input. Results for Section 2 were less consistent. None of the Section 2 studies reported controlled or randomized designs. With the exception of four studies, all included participants were younger than 25 years of age. Eight of the 16 social networking studies reported positive results for depression-related outcomes. The remaining studies were either mixed or negative. Findings for online support groups tended to be more positive; however, noteworthy risks were identified. CONCLUSIONS: Online interventions with a broad cognitive behavioral focus appear to be promising in reducing depression symptomology in young people. Further research is required into the effectiveness of online interventions delivering cognitive behavioral subcomponents, such as problem-solving therapy. Evidence for the use of social networking is less compelling, although limited by a lack of well-designed studies and social networking interventions. A range of future social networking therapeutic opportunities are highlighted

Reviving the Philippine Economy under a Responsible New Normal

After the reclassification of areas under enhanced community quarantine (ECQ) to general community quarantine (GCQ), the urgent task for the Philippine government is to provide an exit plan to revive the Philippine economy. Given the significant economic damage resulting from the shutdown of roughly 75 percent of the country’s total production in the National Capital Region (NCR) and in the CALABARZON and Central Luzon areas, a gradual reopening of the economy will be necessary to prevent further economic damage that could not only be difficult to repair, but also long to overcome. Indeed, based on recent directives from the government, a substantial number of industries and services have thus been allowed to operate in both the ECQ and GCQ areas. However, as the Philippine government begins to calibrate the opening of sectors, there remain concerns as to how this process will affect jobs and livelihoods now and beyond. In this context, an economic recovery plan that talks about short-term, a transition, and full recovery phases— encompassing a revision of the current Philippine Development Plan without losing sight of the long-term goals envisioned in Ambisyon Natin 2040— is still needed. Indeed, a key component of AmBisyon 2040 has been of building resiliency over the long-term, which includes resiliency in health and economic shocks apart from natural disasters. At the same time, this recovery plan should also be accompanied by structural reforms to enhance its implementation. The Department of Finance has crafted a four-pillar socio-economic strategy aimed at: (a) supporting the more vulnerable sectors of society; (b) increasing medical resources to contain the virus and offer safety to front-liners; (c) keeping the economy afloat through financial emergency initiatives; and (d) creating jobs and sustaining the economy. Yet while enumerating the costs of these plans, the said strategy lacked details on how the country could achieve some of the goals without the availability of widespread testing and adequate health facilities. Loan guarantees, cash transfers, and other forms of subsidies can revive disrupted supply chains but cannot restore productivity in the middle of a persisting health crisis, while the uncertainty of a possible outbreak can keep workers from supplying goods and services. It is crucial to have these programs and institutions in place since a number of cities, regions and provinces have started to reopen. A modified community quarantine without the necessary health system investments, protection measures, and economic recovery plan risks amounting to an unregulated herd immunity strategy. Opting for herd immunity allows governments to blame the failure of the health and economic system on the virus, rather than on bad governance. Under current GCQ protocols, the burden on containing the virus is mostly transferred to the public. Unless the government provides mass testing, the problem of information is aggravated, probably raising the transmission risks. Moreover, unregulated herd immunity will be differentially felt by the poor. As healthy workers may recover their earnings from the modified quarantine, the poor, who have limited access to the health services and are thus more susceptible to the virus, are unlikely to benefit from this system. In effect, this will only exacerbate the inequality that prevails in the country. Moving towards a responsible new normal requires a strategy that addresses both people’s wellbeing and the socio-economic weaknesses exposed by COVID-19. Thus, the strategy should have the following elements

Generating Operative Workflows for Vestibular Schwannoma Resection: A Two-Stage Delphi's Consensus in Collaboration with the British Skull Base Society. Part 2: The Translabyrinthine Approach

Objective An operative workflow systematically compartmentalizes operations into hierarchal components of phases, steps, instrument, technique errors, and event errors. Operative workflow provides a foundation for education, training, and understanding of surgical variation. In this Part 2, we present a codified operative workflow for the translabyrinthine approach to vestibular schwannoma resection. Methods A mixed-method consensus process of literature review, small-group Delphi's consensus, followed by a national Delphi's consensus was performed in collaboration with British Skull Base Society (BSBS). Each Delphi's round was repeated until data saturation and over 90% consensus was reached. Results Seventeen consultant skull base surgeons (nine neurosurgeons and eight ENT [ear, nose, and throat]) with median of 13.9 years of experience (interquartile range: 18.1 years) of independent practice participated. There was a 100% response rate across both the Delphi rounds. The translabyrinthine approach had the following five phases and 57 unique steps: Phase 1, approach and exposure; Phase 2, mastoidectomy; Phase 3, internal auditory canal and dural opening; Phase 4, tumor debulking and excision; and Phase 5, closure. Conclusion We present Part 2 of a national, multicenter, consensus-derived, codified operative workflow for the translabyrinthine approach to vestibular schwannomas. The five phases contain the operative, steps, instruments, technique errors, and event errors. The codified translabyrinthine approach presented in this manuscript can serve as foundational research for future work, such as the application of artificial intelligence to vestibular schwannoma resection and comparative surgical research

Trial of Dexamethasone for Chronic Subdural Hematoma

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.)

A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial)

BACKGROUND: Chronic subdural haematoma is a collection of ‘old blood’ and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. OBJECTIVE: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. DESIGN: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. SETTING: Neurosurgical units in the UK. PARTICIPANTS: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. INTERVENTIONS: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. MAIN OUTCOMES MEASURES: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0–3) or an unfavourable (score of 4–6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. RESULTS: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (−8.2%, 95% confidence interval −13.3% to −3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be –£97.19. CONCLUSIONS: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group