Low-latency gravitational wave alert products and their performance at the time of the fourth LIGO-Virgo-KAGRA observing run.

Multimessenger searches for binary neutron star (BNS) and neutron star-black hole (NSBH) mergers are currently one of the most exciting areas of astronomy. The search for joint electromagnetic and neutrino counterparts to gravitational wave (GW)s has resumed with ALIGO's, AdVirgo's and KAGRA's fourth observing run (O4). To support this effort, public semiautomated data products are sent in near real-time and include localization and source properties to guide complementary observations. In preparation for O4, we have conducted a study using a simulated population of compact binaries and a mock data challenge (MDC) in the form of a real-time replay to optimize and profile the software infrastructure and scientific deliverables. End-toend performance was tested, including data ingestion, running online search pipelines, performing annotations, and issuing alerts to the astrophysics community. We present an overview of the low-latency infrastructure and the performance of the data products that are now being released during O4 based on the MDC. We report the expected median latency for the preliminary alert of full bandwidth searches (29.5 s) and show consistency and accuracy of released data products using the MDC. We report the expected median latency for triggers from early warning searches (-3.1 s), which are new in O4 and target neutron star mergers during inspiral phase. This paper provides a performance overview for LIGO-Virgo-KAGRA (LVK) low-latency alert infrastructure and data products using theMDCand serves as a useful reference for the interpretation of O4 detections.

n-Bu4NI/K2S2O8 Mediated Csp2-Csp2 Bond Cleavage - Transformylation from p-Anisaldehyde to Primary Amides.

n-Bu4NI/K2S2O8 mediated transformylation from p-anisaldehyde to primary amides is reported. The mechanistic studies suggest the reaction occurs via a single electron transfer pathway. Based on the DFT electronic structure calculations of various reaction pathways, the most plausible mechanism involves the formation of a phenyl radical cation and an arenium ion as the key intermediates. It represents the first example where p-anisaldehyde is employed as a formyl source via a non-metal mediated Csp2-Csp2 bond cleavage.

n-Bu4NI/K2S2O8-MEDIATED C-N COUPLING BETWEEN ALDEHYDES AND AMIDES.

n-Bu4NI/K2S2O8 mediated C-N coupling between aldehydes and amides is reported. A strong electronic effect is observed on the aromatic aldehyde substrates. The transformylation from aldehyde to amide takes place exclusively when an aromatic aldehyde bears electron-donating groups at either the ortho or para position of the formyl group, while the cross-dehydrogenative coupling dominates in the absence of these groups. Both the density functional theory (DFT) thermochemistry calculations and experimental data support the proposed single electron transfer mechanism with the formation of an acyl radical intermediate in the cross-dehydrogenative coupling. The n-Bu4NI/K2S2O8 mediated oxidative cyclization between 2-aminobenzamide and aldehydes is also reported, with four quinazolin-4(3H)-ones prepared in 65-99% yields.

Geospatial analysis and participant characteristics associated with colorectal cancer screening participation in Alberta, Canada: a population-based cross-sectional study.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in Canada and early detection can prevent deaths through screening. However, CRC screening in Alberta, Canada remains suboptimal and varies by sociodemographic and health system characteristics, as well as geographic location. This study aimed to further the understanding of these participant and health system characteristics associated with CRC screening in Alberta and identify clusters of regions with higher rates of overdue or unscreened individuals. METHODS: We included Albertans aged 52 to 74 as of December 31, 2019 (index date) and we used data from administrative health data sources and linked to the Alberta Colorectal Cancer Screening Program database to determine colorectal cancer screening rates. We used multivariable multinomial logistic regression analysis to investigate the relationship between sociodemographic, health system characteristics and participation in CRC screening. We used optimized Getis-Ord Gi* hot-spot analysis to identify hot and cold-spots in overdue for and no record of CRC screening. RESULTS: We included 919,939 Albertans, of which 65% were currently up to date on their CRC screening, 21% were overdue, and 14% had no record of CRC screening. Compared to Albertans who were currently up to date, those who were in older age groups, those without a usual provider of care, those who were health system non-users, and those living in more deprived areas were more likely to have no record of screening. Areas with high number of Albertans with no record of screening were concentrated in the North and Central zones. CONCLUSIONS: Our study showed important variation in colorectal cancer screening participation across sociodemographic, health system and geographical characteristics and identified areas with higher proportions of individuals who have no record of screening or are under-screened in Alberta, Canada.

Accuracy and safety of in-house surgeon-designed three-dimensional-printed patient-specific implants for wafer-less Le Fort I osteotomy.

OBJECTIVES: The design and fabrication of three-dimensional (3D)-printed patient-specific implants (PSIs) for orthognathic surgery are customarily outsourced to commercial companies. We propose a protocol of designing PSIs and surgical guides by orthognathic surgeons-in-charge instead for wafer-less Le Fort I osteotomy. The aim of this prospective study was to evaluate the accuracy and post-operative complications of PSIs that are designed in-house for Le Fort I osteotomy. MATERIALS AND METHODS: The post-operative cone beam computer tomography (CBCT) model of the maxilla was superimposed to the virtual surgical planning to compare the discrepancies of pre-determined landmarks, lines, and principal axes between the two models. Twenty-five patients (12 males, 13 females) were included. RESULTS: The median linear deviations of the post-operative maxilla of the x, y, and z axes were 0.74 mm, 0.75 mm, and 0.72 mm, respectively. The deviations in the principal axes for pitch, yaw, and roll were 1.40°, 0.90°, and 0.60°, respectively. There were no post-operative complications related to the PSIs in the follow-up period. CONCLUSIONS: The 3D-printed PSIs designed in-house for wafer-less Le Fort I osteotomy are accurate and safe. CLINICAL RELEVANCE: Its clinical outcomes and accuracy are comparable to commercial PSIs for orthognathic surgery. TRIAL REGISTRATION: Clinical trial registration number: HKUCTR-2113. Date of registration: 29 July 2016.

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1): a pragmatic stepped-wedge, cluster randomized controlled registry trial.

BACKGROUND: The shortage of available organs for life-saving transplants persists worldwide. While a majority support donating their organs or tissue when they die, many have not registered their wish to do so. When registered, next of kin are much more likely to follow-through with the decision to donate. In many countries, most people visit their family physician office each year and this setting is a promising, yet underused, site where more people could register for deceased organ donation. Our primary aim was to evaluate the effectiveness of an intervention to promote organ donation registration in family physician's offices. METHODS: We developed an intervention to address barriers and enablers to organ donation registration that involved physician office reception staff inviting patients to register on a tablet in the waiting room while they waited for their appointment. We conducted a cross-sectional stepped-wedge cluster randomized controlled registry trial to evaluate the intervention. We recruited six family physician offices in Canada. All offices began with usual care and then every two weeks, one office (randomly assigned) started the intervention until all offices delivered the intervention. The primary outcome was registration for deceased organ donation in the provincial organ registration registry, assessed within the 7 days of the physician visit. At the end of the trial, we also conducted interviews with clinic staff to assess any barriers and enablers to delivering the intervention. RESULTS: The trial involved 24,616 patient visits by 13,562 unique patients: 12,484 visits in the intervention period and 12,132 in the control period. There was no statistically significant difference in the percentage of patients registered for deceased organ donation in the intervention versus control period (48.0% vs 46.2%; absolute difference after accounting for the secular trend: 0.12%; 95% CI: - 2.30, 2.54; p=0.92). Interviews with clinic staff indicated location of the tablet within a waiting room, patient rapport, existing registration, confidence and motivation to deliver the intervention and competing priorities as barriers and enablers to delivery. CONCLUSIONS: Our intervention did not increase donor registration. Nonetheless, family physician offices may still remain a promising setting to develop and evaluate better interventions to increase organ donation registration. TRIAL REGISTRATION: NCT03213171.

Interventions for increasing solid organ donor registration.

BACKGROUND: A solution for increasing the number of available organs for transplantation is to encourage more individuals to register a commitment for deceased organ donation. However, the percentage of the population registered for organ donation remains low in many countries. OBJECTIVES: To evaluate the benefits and harms of various interventions used to increase deceased organ donor registration. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 11 August 2020 through contact with an Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs), cluster RCTs and quasi-RCTs of interventions to promote deceased organ donor registration. We included studies if they measured self-reported or verified donor registration, intention to donate, intention to register a decision or number of individuals signing donor cards as outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently assessed retrieved studies and extracted data from included studies. We assessed studies for risk of bias. We obtained summary estimates of effect using a random-effects model and expressed results as risk ratios (RR) (95% confidence intervals; CI) for dichotomous outcomes and mean difference (MD; 95% CI) or standardised mean difference (SMD; 95% CI) for continuous outcomes. In multi-arm trials, data were pooled to create single pair-wise comparisons. Analyses were stratified by specific intervention setting where available. MAIN RESULTS: Our search strategy identified 46 studies (47 primary articles, including one abstract) comprising 24 parallel RCTs, 19 cluster RCTs and 3 quasi-RCTs. Sample sizes ranged from 138 to 1,085,292 (median = 514). A total of 16 studies measured registration behaviour, 27 measured intention to register/donate and three studies measured both registration behaviour and intention to register. Interventions were delivered in a variety of different settings: schools (14 studies), driver's motor vehicle (DMV) centres (5), mail-outs (4), primary care centres (3), workplaces (1), community settings (7) and general public (12). Interventions were highly varied in terms of their content and included strategies such as educational sessions and videos, leveraging peer leaders, staff training, message framing, and priming. Most studies were rated as having high or unclear risk of bias for random sequence generation and allocation concealment and low risk for the remainder of the domains. Data from 34/46 studies (74%) were available for meta-analysis. Low certainty evidence showed organ donation registration interventions had a small overall effect on improving registration behaviour (16 studies, 1,294,065 participants: RR 1.30, 95% CI 1.19 to 1.43, I2 = 84%), intention to register/donate (dichotomous) (10 studies, 10,838 participants: RR 1.21, 95% CI 1.03 to 1.42, I2 = 91%) and intention to register/donate (continuous) (9 studies, 3572 participants: SMD 0.23, 95% CI 0.11 to 0.36, I2 = 67%). Classroom-based interventions delivered in a lecture format by individuals from the transplant community may be effective at increasing intention to register/donate (3 studies, 675 participants: RR 1.33, 95% CI 1.15 to 1.55, I² = 0%). Community interventions targeting specific ethnic groups were generally effective at increasing registration rates (k = 5, n = 4186; RR 2.14, 95% CI 1.35 to 3.40, I² = 85%), although heterogeneity was high. In particular, interventions delivered in the community by trained peer-leaders appear to be effective (3 studies, 3819 participant: RR 2.09, 95% CI 1.08 to 4.06, I² = 87%), although again, the data lacked robustness. There was some evidence that framing messages (e.g. anticipated regret) and priming individuals (e.g. reciprocity) in a certain way may increase intention to register/donate, however, few studies measured this effect on actual registration. Overall, the studies varied significantly in terms of design, setting, content and delivery. Selection bias was evident and a quarter of the studies could not be included in the meta-analysis due to incomplete outcome data reporting. No adverse events were reported. AUTHORS' CONCLUSIONS: In our review, we identified a variety of approaches used to increase organ donor registration including school-based educational sessions and videos, leveraging peer leaders in the community, DMV staff training, targeted messaging and priming. The variability in outcome measures used and incompleteness in reporting meant that most data could not be combined for analysis. When data were combined, overall effect sizes were small in favour of intervention groups over controls, however, there was significant variability in the data. There was some evidence that leveraging peer-leaders in the community to deliver organ donation education may improve registration rates and classroom-based education from credible individuals (i.e. members of the transplant community) may improve intention to register/donate, however, there is no clear evidence favouring any particular approach. There was mixed evidence for simple, low-intensity interventions utilising message framing and priming. However, it is likely that interest in these strategies will persist due to their reach and scalability. Further research is therefore required to adequately address the question of the most effective interventions for increasing deceased organ donor registration.

Effects of hospital funding reform on wait times for hip fracture surgery: a population-based interrupted time-series analysis.

BACKGROUND: Health care funding reforms are being used worldwide to improve system performance but may invoke unintended consequences. We assessed the effects of introducing a targeted hospital funding model, based on fixed price and volume, for hip fractures. We hypothesized the policy change was associated with reduction in wait times for hip fracture surgery, increase in wait times for non-hip fracture surgery, and increase in the incidence of after-hours hip fracture surgery. METHODS: This was a population-based, interrupted time series analysis of 49,097 surgeries for hip fractures, 10,474 for ankle fractures, 1,594 for tibial plateau fractures, and 40,898 for appendectomy at all hospitals in Ontario, Canada between April 2012 and March 2017. We used segmented regression analysis of interrupted monthly time series data to evaluate the impact of funding reform enacted April 1, 2014 on wait time for hip fracture repair (from hospital presentation to surgery) and after-hours provision of surgery (occurring between 1700 and 0700 h). To assess potential adverse consequences of the reform, we also evaluated two control procedures, ankle and tibial plateau fracture surgery. Appendectomy served as a non-orthopedic tracer for assessment of secular trends. RESULTS: The difference (95 % confidence interval) between the actual mean wait time and the predicted rate had the policy change not occurred was - 0.46 h (-3.94 h, 3.03 h) for hip fractures, 1.46 h (-3.58 h, 6.50 h) for ankle fractures, -3.22 h (-39.39 h, 32.95 h) for tibial plateau fractures, and 0.33 h (-0.57 h, 1.24 h) for appendectomy (Figure 1; Table 3). The difference (95 % confidence interval) between the actual and predicted percentage of surgeries performed after-hours - 0.90 % (-3.91 %, 2.11 %) for hip fractures, -3.54 % (-11.25 %, 4.16 %) for ankle fractures, 7.09 % (-7.97 %, 22.14 %) for tibial plateau fractures, and 1.07 % (-2.45 %, 4.59 %) for appendectomy. CONCLUSIONS: We found no significant effects of a targeted hospital funding model based on fixed price and volume on wait times or the provision of after-hours surgery. Other approaches for improving hip fracture wait times may be worth pursuing instead of funding reform.

ESRD among Immigrants to Ontario, Canada: A Population-Based Study.

Background The epidemiology of ESRD requiring maintenance dialysis (ESRD-D) in large, diverse immigrant populations is unclear.Methods We estimated ESRD-D prevalence and incidence among immigrants in Ontario, Canada. Adults residing in Ontario in 2014 were categorized as long-term Canadian residents or immigrants according to administrative health and immigration datasets. We determined ESRD-D prevalence among these adults and calculated age-adjusted prevalence ratios (PRs) comparing immigrants to long-term residents. Among those who immigrated to Ontario between 1991 and 2012, age-adjusted ESRD-D incidence was calculated by world region and country of birth, with immigrants from Western nations as the referent group.Results Among 1,902,394 immigrants and 8,860,283 long-term residents, 1700 (0.09%) and 8909 (0.10%), respectively, presented with ESRD-D. Age-adjusted ESRD-D prevalence was higher among immigrants from sub-Saharan Africa (PR, 2.17; 95% confidence interval [95% CI], 1.84 to 2.57), Latin America and the Caribbean (PR, 2.11; 95% CI, 1.90 to 2.34), South Asia (PR, 1.45; 95% CI, 1.32 to 1.59), and East Asia and the Pacific (PR, 1.34; 95% CI, 1.22 to 1.46). Immigrants from Somalia (PR, 4.18; 95% CI, 3.11 to 5.61), Trinidad and Tobago (PR, 2.88; 95% CI, 2.23 to 3.73), Jamaica (PR, 2.88; 95% CI, 2.40 to 3.44), Sudan (PR, 2.84; 95% CI, 1.53 to 5.27), and Guyana (PR, 2.69; 95% CI, 2.19 to 3.29) had the highest age-adjusted ESRD-D PRs relative to long-term residents. Immigrants from these countries also exhibited higher age-adjusted ESKD-D incidence relative to Western Nations immigrants.Conclusions Among immigrants in Canada, those from sub-Saharan Africa and the Caribbean have the highest ESRD-D risk. Tailored kidney-protective interventions should be developed for these susceptible populations.

Isotretinoin-induced acne fulminans without systemic symptoms with concurrent exuberant granulation tissue.

Acne fulminans is a severe form of acne characterized by painful, inflammatory nodules that progress into ulcers and concurrent systemic symptoms. Treatment of acne with isotretinoin can precipitate a syndrome called isotretinoin-induced acne fulminans without systemic symptoms. An exuberant granulation tissue response, another known adverse event associated with isotretinoin, can occur concurrently, inhibiting wound repair and complicating treatment. We report a case of isotretinoin-induced acne fulminans without systemic symptoms with exuberant granulation tissue response that was treated successfully with topical clobetasol ointment.

A pediatric case of squamous cell cancer in situ in the setting of sclerodermatous graft-versus-host disease and voriconazole treatment.

Sclerodermatous graft-versus-host disease is a subtype of cutaneous chronic graft-versus-host disease that is characterized by sclerosis of the skin and subcutaneous tissue, resulting in debilitating contractures, among other life-threatening complications. Children with sclerodermatous graft-versus-host disease are at high risk of developing nonmelanoma skin cancer because of several risk factors, including young age at transplantation, prolonged immunosuppression, and exposure to photosensitizing antimicrobial prophylaxis such as voriconazole. The immunosuppression required to treat sclerodermatous graft-versus-host disease makes effectively treating nonmelanoma skin cancer and sclerodermatous graft-versus-host disease in the same patient challenging. We describe a challenging case of a 6-year-old boy with a history of sclerodermatous graft-versus-host disease and voriconazole exposure presenting with squamous cell carcinoma in situ on the left temple and actinic keratoses on the scalp treated with topical chemotherapy agents.

Improving safety culture in hospitals: Facilitators and barriers to implementation of Systemic Falls Investigative Method (SFIM).

OBJECTIVE: The purpose of this study was to assess the facilitators and barriers to implementation of the Systemic Falls Investigative Method (SFIM) on selected hospital units. DESIGN: A cross-sectional explanatory mixed methods design was used to converge results from a standardized safety culture survey with themes that emerged from interviews and focus groups. Findings were organized by six elements of the Ottawa Model of Research Use framework. SETTING: A geriatric rehabilitation unit of an acute care hospital and a neurological unit of a rehabilitation hospital were selected purposefully due to the high frequency of falls. PARTICIPANTS: Hospital staff who took part in: surveys (n = 39), interviews (n = 10) and focus groups (n = 12), and 38 people who were interviewed during falls investigations: fallers, family, unit staff and hospital management. INTERVENTION: Implementation of the SFIM to investigate fall occurrences. MAIN OUTCOME MEASURE(S): Percent of positive responses on the Modified Stanford Patient Safety Culture Survey Instrument converged with qualitative themes on facilitators and barriers for intervention implementation. RESULTS: Both hospital units had an overall poor safety culture which hindered intervention implementation. Facilitators were hospital accreditation, strong emphasis on patient safety, infrastructure and dedicated champions. Barriers included heavy workloads, lack of time, lack of resources and poor communication. CONCLUSIONS: Successful implementation of SFIM requires regulatory and organizational support, committed frontline staff and allocation of resources to identify active causes and latent contributing factors to falls. System-wide adjustments show promise for promotion of safety culture in hospitals where falls happen regularly.

Inpatient management of children with recessive dystrophic epidermolysis bullosa: A review.

Recessive dystrophic epidermolysis bullosa is a disorder marked by skin and mucosal blistering after minimal trauma. Even the most routine procedures in the hospital, if done incorrectly, can precipitate extensive skin loss, pain, and scarring. Most providers have little experience working with patients with this degree of skin fragility. When a person with recessive dystrophic epidermolysis bullosa is admitted to the hospital, there are multiple considerations to keep in mind while strategizing an effective care plan: avoidance of new blisters with a "hands-off" approach; careful consideration of all indwelling devices; symptomatic management of pain, itch, and anxiety; coordination of dressing changes; aggressive treatment of skin infections; environmental and staffing considerations; and awareness of other chronic complications that affect care, such as anemia, malnutrition, and chronic pain. To minimize discomfort for patients with recessive dystrophic epidermolysis bullosa during the hospital stay, inpatient care teams should understand these considerations and modify the care plan accordingly. Prior preparation by the hospital facility and inpatient care team will facilitate the delivery of safe and effective care and greatly improve the overall patient experience.

Bullous systemic lupus erythematosus in a 6-year-old boy.

Bullous systemic lupus erythematosus (BSLE) is a rare subepidermal blistering disorder characterized by an acute vesiculobullous eruption in a subset of individuals with systemic lupus erythematosus. BSLE most commonly affects young women and only rarely affects children. Herein we report a rare case of BSLE in a 6-year-old boy.

Successful Treatment of Pediatric Alopecia Areata of the Scalp Using Topical Bimatoprost.

Alopecia areata (AA) is a genetic and immune-mediated disease that targets anagen hair follicles. Despite limited evidence supporting the efficacy of corticosteroid treatments, they are often prescribed as first-line therapy because of their favorable safety profile. Prostaglandin analogues are currently being studied as an alternate therapy for scalp AA in adults. Herein we present a case of steroid-resistant multifocal AA that was successfully treated with topical bimatoprost.

Evolution of Reporting P Values in the Biomedical Literature, 1990-2015.

IMPORTANCE: The use and misuse of P values has generated extensive debates. OBJECTIVE: To evaluate in large scale the P values reported in the abstracts and full text of biomedical research articles over the past 25 years and determine how frequently statistical information is presented in ways other than P values. DESIGN: Automated text-mining analysis was performed to extract data on P values reported in 12,821,790 MEDLINE abstracts and in 843,884 abstracts and full-text articles in PubMed Central (PMC) from 1990 to 2015. Reporting of P values in 151 English-language core clinical journals and specific article types as classified by PubMed also was evaluated. A random sample of 1000 MEDLINE abstracts was manually assessed for reporting of P values and other types of statistical information; of those abstracts reporting empirical data, 100 articles were also assessed in full text. MAIN OUTCOMES AND MEASURES: P values reported. RESULTS: Text mining identified 4,572,043 P values in 1,608,736 MEDLINE abstracts and 3,438,299 P values in 385,393 PMC full-text articles. Reporting of P values in abstracts increased from 7.3% in 1990 to 15.6% in 2014. In 2014, P values were reported in 33.0% of abstracts from the 151 core clinical journals (n = 29,725 abstracts), 35.7% of meta-analyses (n = 5620), 38.9% of clinical trials (n = 4624), 54.8% of randomized controlled trials (n = 13,544), and 2.4% of reviews (n = 71,529). The distribution of reported P values in abstracts and in full text showed strong clustering at P values of .05 and of .001 or smaller. Over time, the "best" (most statistically significant) reported P values were modestly smaller and the "worst" (least statistically significant) reported P values became modestly less significant. Among the MEDLINE abstracts and PMC full-text articles with P values, 96% reported at least 1 P value of .05 or lower, with the proportion remaining steady over time in PMC full-text articles. In 1000 abstracts that were manually reviewed, 796 were from articles reporting empirical data; P values were reported in 15.7% (125/796 [95% CI, 13.2%-18.4%]) of abstracts, confidence intervals in 2.3% (18/796 [95% CI, 1.3%-3.6%]), Bayes factors in 0% (0/796 [95% CI, 0%-0.5%]), effect sizes in 13.9% (111/796 [95% CI, 11.6%-16.5%]), other information that could lead to estimation of P values in 12.4% (99/796 [95% CI, 10.2%-14.9%]), and qualitative statements about significance in 18.1% (181/1000 [95% CI, 15.8%-20.6%]); only 1.8% (14/796 [95% CI, 1.0%-2.9%]) of abstracts reported at least 1 effect size and at least 1 confidence interval. Among 99 manually extracted full-text articles with data, 55 reported P values, 4 presented confidence intervals for all reported effect sizes, none used Bayesian methods, 1 used false-discovery rates, 3 used sample size/power calculations, and 5 specified the primary outcome. CONCLUSIONS AND RELEVANCE: In this analysis of P values reported in MEDLINE abstracts and in PMC articles from 1990-2015, more MEDLINE abstracts and articles reported P values over time, almost all abstracts and articles with P values reported statistically significant results, and, in a subgroup analysis, few articles included confidence intervals, Bayes factors, or effect sizes. Rather than reporting isolated P values, articles should include effect sizes and uncertainty metrics.

Clinical Next Generation Sequencing for Precision Medicine in Cancer.

Rapid adoption of next generation sequencing (NGS) in genomic medicine has been driven by low cost, high throughput sequencing and rapid advances in our understanding of the genetic bases of human diseases. Today, the NGS method has dominated sequencing space in genomic research, and quickly entered clinical practice. Because unique features of NGS perfectly meet the clinical reality (need to do more with less), the NGS technology is becoming a driving force to realize the dream of precision medicine. This article describes the strengths of NGS, NGS panels used in precision medicine, current applications of NGS in cytology, and its challenges and future directions for routine clinical use.

Systematic search and review procedures: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVES: To update the last best-evidence synthesis conducted by the World Health Organization Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation in 2002; and to describe the course, identify prognostic factors, determine long-term sequelae, identify effects of interventions for mild traumatic brain injury (MTBI), identify knowledge gaps in the literature, and make recommendations for future research. DATA SOURCES: MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health, and SPORTDiscus were searched between 2001 and 2012. Inclusion criteria included published peer-reviewed articles in English and 5 other languages. References were also identified from relevant reviews and meta-analyses and the bibliographies of eligible articles. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined inclusion/exclusion criteria. Studies had to have at least 30 MTBI cases and assess outcomes relevant to prognosis after MTBI. DATA EXTRACTION: Eligible studies were critically appraised using modified Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles (ie, with a low risk of bias) into evidence tables. DATA SYNTHESIS: The evidence was synthesized qualitatively according to modified SIGN criteria and prioritized according to design as exploratory or confirmatory. The evidence was organized into separate articles according to population (eg, adults, children, and athletes) and outcomes (eg, risk of dementia after MTBI). CONCLUSIONS: After 77,914 records were screened, 299 articles were eligible and reviewed. Of these, 101 (34%) were accepted as scientifically admissible and form the basis of our findings, which are organized into 10 articles in this supplement. These reviews present the best available evidence on MTBI prognosis, but more research is needed.