Quantifying Intra- and Interlimb Use During Unimanual and Bimanual Tasks in Persons with Hemiparesis Post-Stroke

Background Individuals with hemiparesis post-stroke often have difficulty with tasks requiring upper extremity (UE) intra- and interlimb use, yet methods to quantify both are limited. Objective To develop a quantitative yet sensitive method to identify distinct features of UE intra- and interlimb use during task performance. Methods Twenty adults post-stroke and 20 controls wore five inertial sensors (wrists, upper arms, sternum) during 12 seated UE tasks. Three sensor modalities (acceleration, angular rate of change, orientation) were examined for three metrics (peak to peak amplitude, time, and frequency). To allow for comparison between sensor data, the resultant values were combined into one motion parameter, per sensor pair, using a novel algorithm. This motion parameter was compared in a group-by-task analysis of variance as a similarity score (0–1) between key sensor pairs: sternum to wrist, wrist to wrist, and wrist to upper arm. A use ratio (paretic/non-paretic arm) was calculated in persons post-stroke from wrist sensor data for each modality and compared to scores from the Adult Assisting Hand Assessment (Ad-AHA Stroke) and UE Fugl-Meyer (UEFM). Results A significant group × task interaction in the similarity score was found for all key sensor pairs. Post-hoc tests between task type revealed significant differences in similarity for sensor pairs in 8/9 comparisons for controls and 3/9 comparisons for persons post stroke. The use ratio was significantly predictive of the Ad-AHA Stroke and UEFM scores for each modality. Conclusions Our algorithm and sensor data analyses distinguished task type within and between groups and were predictive of clinical scores. Future work will assess reliability and validity of this novel metric to allow development of an easy-to-use app for clinicians

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

The magnificent seven : A proposal for modest revision of the Van der Voo (1990) quality index

Thirty years ago, Rob Van der Voo proposed an elegant and simple system for evaluating the quality of paleomagnetic data. As a second-year Ph.D. student, the lead author remembers Rob waxing philosophical about the need to have an appropriate, but not overly rigid evaluation system. The end result was a 7-point system that assigned a (1) or (0) for any paleomagnetic result based on objective criteria. The goal was never to reject or blindly accept any particular result, but merely to indicate the degree of quality for any paleomagnetic pole. At the time, the global paleomagnetic database was burgeoning and it was deemed useful to rank older paleo magnetic results with the newer data being developed in modern laboratories. Van der Voo's, 1990 paper launched a silent revolution in paleomagnetism. Researchers began to evaluate their data against those seven criteria with the anticipation that reviewers would be similarly critical. Today, paleomagnetism is a mature science. Our methods, analyses, and results are more sophisticated than they were 30 years ago. Therefore, we feel it is appropriate to revisit the Van der Voo (1990) criteria in light of those developments. We hope to honor the intention of the original paper by keeping the criteria simple and easy to evaluate while also acknowledging the advances in science. This paper aims to update the criteria and modernize the process. We base our changes on advances in paleomagnetism and geochronology with a faithful adherence to the simplicity of the original publication. We offer the "Reliability" or "R" index as the next generation of the Van der Voo "Quality" or "Q" index. The new R-criteria evaluate seven different information items for each paleomagnetic pole including age, statistical requirements, identification of magnetic carriers, field tests, structural integrity, presence of reversals and an evaluation for possible remagnetization.Peer reviewe

Does Health Affect Party Identification? : Evidence from German Panel Data

Recent research has shown the effect of health on voter turnout, arguing that attenuated health depresses voting. However, we know little about how health is connected to the psychological factors, such as party identification, that precede actual political participation. Employing data from the German Socio-Economic Panel (SOEP), we show that when a person’s health deteriorates, the degree of partisan attachment declines, whereas health improvement does not automatically restore the level of party identification to previous levels.Peer reviewe

Getting shot of elves: healing, witchcraft and fairies in the Scottish witchcraft trials

This paper re-examines the evidence of the Scottish witchcraft trials for beliefs associated by scholars with "elf-shot." Some supposed evidence for elf-shot is dismissed, but other material illuminates the interplay between illness, healing and fairy-lore in early modern Scotland, and the relationship of these beliefs to witchcraft itself

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

Social Work and Countering Violent Extremism in Sweden and the UK

Social Work in Europe, is now being tasked with managing the “problems” of terrorism, i.e supporting those affected by terrorist attacks, managing returnees affiliated with Terrorist groups in the Middle East, or, as will be discussed here, identifying those at risk from radicalisation and extremism. Both Britain and Sweden have Counter-Terrorism policies, but recent developments in both countries, have made it a statutory requirement for social workers, to work within such policies. This paper seeks to explore the policies in both countries utilising a comparative approach, to consider the similarities in not only policy and practice, but also in the ethical consequences such policies pose for social workers across Europe. The exploration considers; the extent to which anti-radicalisation policies influence social work practices in Sweden and the UK and how they might undermine social work as a human rights profession. The results indicate that anti-radicalisation policies run the risk of reducing social work to become a ‘policing profession’ practicing social control. This has substantial consequences for social work and its global ethics, which should be considered and struggled against by social workers committed to principles of social justice and human rights

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n=180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants. Emerging SARS-CoV-2 variants contain mutations in the spike protein that may affect vaccine efficacy. Here, Jalkanen et al. show, using sera from 180 BNT162b2-vaccinated health care workers, that neutralization of SARS-CoV2 variant B.1.1.7 is not affected, while neutralization of B.1.351 variant is five-fold reduced.Peer reviewe

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants