Durable response using regorafenib in an elderly patient with metastatic colorectal cancer: case report.

Regorafenib, an oral multikinase inhibitor, was approved in September 2012 by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer. Since this time, however, few case reports outlining real-world usage have been published in the literature. Here, we detail the clinical history of an elderly woman with KRAS wild-type colon cancer who received regorafenib after prior treatment with other agents. We show that by employing dose modification strategies to address adverse events, this patient was able to remain on therapy for 11 months and achieve stable disease

Are 'unbiased' forecasts really unbiased? Another look at the Fed forecasts

This paper reconciles contradictory findings obtained from forecast evaluations: the existence of systematic errors and the failure to reject rationality in the presence of such errors. Systematic errors in one economic state may offset the opposite types of errors in the other state such that the null of rationality is not rejected. A modified test applied to the Fed forecasts shows that the forecasts were ex post biased.Greenbook Forecasts, forecast evaluation, systematic errors

Can the Fed Predict the State of the Economy?

Recent research has documented that the Federal Reserve produces systematic errors in forecasting inflation, real GDP growth, and the unemployment rate, even though these forecasts are unbiased. We show that these systematic errors reveal that the Fed is “surprised” by real and inflationary cycles. Using a modified Mincer-Zarnowitz regression, we show that the Fed knows the state of the economy for the current quarter, but cannot predict it one quarter ahead.Forecast Evaluation; Federal Reserve; Systematic Errors; Recessions

Strategies to Improve Post-procedural Safe Patient Handoffs

STRATEGIES TO IMPROVE SAFE PATIENT HANDOFFS AND POST PROCEDURAL FLOW During patient transfers from one care unit to another, it is imperative for patient safety and satisfaction that timely and complete communication between staff occurs. In an academic tertiary care medical center, a team consisting of representatives from 6 patient care units used improvement methods of operational excellence to improve patient centered movement. The goal of this project was to improve the percentages of two questions related to information sharing on the FY2018 AHRQ Culture of Patient Safety Survey. Using baseline metrics to reflect the current state of patient wait times and performing a detailed root cause analysis, resulted in the establishment of several countermeasures. Through problem statement development, current state mapping, and fishbone diagramming six joint KPIs were developed for post Kaizen implementation and sustainment. Next steps include reviewing results of the 2018 Culture of Safety Survey, using champions of this work to coach other teams on joint KPI development and implementation and hardwiring ideal state map tool utilizing multiple waves of joint KPIs between 2-3 departments

Non-invasive, Focused Ultrasound-Facilitated Gene Delivery for Optogenetics

Optogenetics, a widely used technique in neuroscience research, is often limited by its invasive nature of application. Here, we present a noninvasive, ultrasound-based technique to introduce optogenetic channels into the brain by temporarily opening the blood-brain barrier (BBB). We demonstrate the efficiency of the method developed and evaluate the bioactivity of the non-invasively introduced channelrhodopsin channels by performing stimulation in freely behaving mice

Bridging the gap between research, policy, and practice: Lessons learned from academic-public partnerships in the CTSA network.

A primary barrier to translation of clinical research discoveries into care delivery and population health is the lack of sustainable infrastructure bringing researchers, policymakers, practitioners, and communities together to reduce silos in knowledge and action. As National Institutes of Health's (NIH) mechanism to advance translational research, Clinical and Translational Science Award (CTSA) awardees are uniquely positioned to bridge this gap. Delivering on this promise requires sustained collaboration and alignment between research institutions and public health and healthcare programs and services. We describe the collaboration of seven CTSA hubs with city, county, and state healthcare and public health organizations striving to realize this vision together. Partnership representatives convened monthly to identify key components, common and unique themes, and barriers in academic-public collaborations. All partnerships aligned the activities of the CTSA programs with the needs of the city/county/state partners, by sharing resources, responding to real-time policy questions and training needs, promoting best practices, and advancing community-engaged research, and dissemination and implementation science to narrow the knowledge-to-practice gap. Barriers included competing priorities, differing timelines, bureaucratic hurdles, and unstable funding. Academic-public health/health system partnerships represent a unique and underutilized model with potential to enhance community and population health

Characterisation of eight cattle with Swyer syndrome by whole‐genome sequencing

Swyer syndrome is where an individual has the karyotype of a typical male yet is phenotypically a female. The lack of a (functional) SRY gene located on the Y‐chromosome is implicated in some cases of the Swyer syndrome, although many Swyer individuals with an apparently fully functional SRY gene have also been documented. The present study undertook whole genome sequence analyses of eight cattle with suspected Swyer syndrome and compared their genome to that of both a control male and female. Sequence analyses coupled with female phenotypes confirmed that all eight individuals had the 60,XY sex reversal Swyer syndrome. Seven of the eight Swyer syndrome individuals had a deletion on the Y chromosome encompassing the SRY gene (i.e., SRY−). The eighth individual had no obvious mutation in the SRY gene (SRY+) or indeed in any reported gene associated with sex reversal in mammals; a necropsy was performed on this individual. No testicles were detected during the necropsy. Histological examination of the reproductive tract revealed an immature uterine body and horns with inactive glandular tissue of normal histological appearance; both gonads were elongated, a characteristic of most reported cases of Swyer in mammals. The flanking sequence of 11 single nucleotide polymorphisms within 10 kb of the SRY gene are provided to help diagnose some cases of Swyer syndrome. These single nucleotide polymorphisms will not, however, detect all cases of Swyer syndrome since, as evidenced from the present study (and other studies), some individuals with the Swyer condition still contain the SRY gene (i.e., SRY+)

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy