Incidence, time course and predictors of impairments relating to caring for the profoundly affected arm after stroke: A systematic review

Background and purpose - A significant number of stroke survivors will not recover the use of their affected arm. A proportion will experience pain, stiffness and difficulty with basic care activities. The purpose of the review was to identify predictors of difficulty caring for the profoundly affected arm and establish the incidence and time-course of the related impairments of pain, spasticity and contracture. Method - Data sources: Databases (PubMED, MEDLINE, AMED, EMBASE, CINAHL and the Cochrane Controlled Trials Register) were searched from inception to December 2013. Additional studies were identified from citation tracking. Review methods: Independent reviewers used pre-defined criteria to identify eligible studies. Quality assessment and risk of bias were assessed using the McMasters Assessment Tool. A narrative evidence synthesis was performed. Results - Thirty-nine articles reporting 34 studies were included. No studies formally measured difficulty caring for the arm, but related impairments were common. Incidence of spasticity in those with weakness ranged from 33% to 78%, shoulder pain affected 22% to 90% and contracture was present in at least 50%. Spasticity and pain appear within 1 week of stroke, and contracture within two weeks. Impairments continued to develop over at least 3–6 months. The most frequent predictors of spasticity and contracture were weakness and reduced motor control, and the risk of pain is most commonly predicted by reduced sensation, shoulder subluxation, weakness and stroke severity. Discussion - There is no published evidence on predicting the likelihood of difficulty caring for the arm following stroke. However, the related impairments of spasticity, pain and contracture are common. Given the time-course of development, clinicians may need not only to intervene early but also be prepared to act over a longer time period. Further research is needed to examine difficulty caring for the arm and the relationship with associated impairments to enable researchers and clinicians to develop targeted interventions

Navigating the Trademark Parody Paradigm: Assessing the Impact of the ‘Bad Spaniels’ Decision on IP Owners, Creatives, and Self-Parody in the Post-Jack Daniel’s Era

This Note explores the blurred lines that now exist at the intersection of safeguarding trademark owners’ rights and protecting the public interest in freedom of expression, with a specific focus on the recent and unprecedented Supreme Court ruling in the ‘Bad Spaniels’ dog chew-toy trademark infringement case. The Supreme Court’s June 2023 decision in Jack Daniel’s v. VIP Products prompts a critical analysis of the once-dominant Rogers v. Grimaldi test, questioning its applicability in determining fair use and parody within the realm of trademark infringement. In examining what lies ahead for the evolving world of trademark law post-‘Bad Spaniels’, this Note draws connections to the cinematic landscape with a dissection of Greta Gerwig’s blockbuster film Barbie (2023). The film serves as a compelling case study, demonstrating a trend in how major IP owners, such as Mattel, have begun strategically engaging in self-parody to bolster their brand through the licensing of IP rights. In the wake of the ‘Bad Spaniels’ ruling and its profound implications on both the legitimacy of the Rogers test and trademark law more holistically, legal scholars are undoubtedly left in the dark as to the continued viability of the Rogers framework and will certainly confront future nuances in the field of trademark law as a result. This Note asserts that perhaps this observed shift in trademark law following the ‘Bad Spaniels’ decision might offer assurances to big-player IP owners, suggesting greater protection for their marks in commercial cases, or alternatively, we will witness a surge in creative industries opting for increased licensing of IP rights, as shown in the case of Mattel’s fully-licensed Barbie (2023) film, to steer clear of infringement issues entirely

Anticancer metallohelices: nanomolar potency and high selectivity

A range of new helicate-like architectures have been prepared via highly diastereoselective self-assembly using readily accessible starting materials. Six pairs of enantiomers [Fe2L3]Cl4.nH2O (L = various bidentate ditopic ligands NN–NN) show very good water solubility and stability. Their activity against a range of cancer cell lines in vitro is structure-dependent and gives IC50 values as low as 40 nM. In an isogenic pair of HCT116 colorectal cancer cells, preferential activity was observed against cell lines that lack functional p53. Selectivity is also excellent, and against healthy human retinal pigment epithelial (ARPE19) and lung fibroblast (WI38) cells IC50 values are nearly three orders of magnitude higher. Cisplatin is unselective in the same tests. The compounds also appear to have low general toxicity in a number of models: there is little if any antimicrobial activity against Methicillin-resistant Staphylococcus aureus and Escherichia coli.; Acanthamoeba polyphaga is unaffected at 25 μg ml-1 (12.5 μM); Manduca sexta larvae showed clear evidence of systemic distribution of the drug, and rather than any observation of adverse effects they exhibited a significant mean weight gain vs controls. Investigation of the mode of action revealed no significant interaction of the molecules with DNA, and stimulation of substantial cell death by apoptosis

RNA Editing at Baseline and Following Endoplasmic Reticulum Stress.

RNA sequences are expected to be identical to the DNA template. However, some RNA processing steps, such as RNA editing, can lead to differences in the RNA sequence that affect the fate of the RNA transcripts or the resultant proteins. My thesis focuses on the regulation of the canonical A-to-G editing and non-canonical RNA-DNA sequence Differences (RDD). My work contributed to the identification of RDDs throughout the human transcriptome. We identified all 12 types of single base differences across multiple individuals and various tissue types. We also detected peptides matching the RDD-encoded sequences suggesting that RDDs are translated into proteins. In subsequent work, we found that the non-canonical RDDs are found in nascent RNA. Through the use of nuclear run-on assays, we found that RDD occurs within seconds of exiting the RNA polymerase complex. Chapters 4 and 5 discuss my study of canonical A-to-G editing mediated by Adenosine Deaminase Acting on RNA (ADAR). First, we found that A-to-G editing levels differ across individuals. I searched for and identified genetic variants whose alleles are associated with editing levels of sites in the same gene. These data demonstrate that ADAR editing is cis regulated and can lead to individual variability in editing levels. Furthermore, by utilizing individual variability in editing and studying the relationship between editing sites, I learned how ADAR edits multiple sites in a given transcript. My data support a model where ADAR edits multiple sites along one side of a double-stranded RNA structure. To learn about the biological significance of RNA editing, I focused on endoplasmic reticulum (ER) stress. I found that editing levels change following ER stress suggesting that these RNA processing steps play a role in the ER stress response. Together, this work sheds light on the regulation of RNA editing and RDDs in the human transcriptome and aids in the understanding of how these processes may play a role in cellular response to stress.PhDHuman GeneticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116721/1/allirich_1.pd

AGN Populations in Large Volume X-ray Surveys: Photometric Redshifts and Population Types found in the Stripe 82X Survey

Multi-wavelength surveys covering large sky volumes are necessary to obtain an accurate census of rare objects such as high luminosity and/or high redshift active galactic nuclei (AGN). Stripe 82X is a 31.3 deg$^2$ X-ray survey with $Chandra$ and $XMM$-Newton observations overlapping the legacy Sloan Digital Sky Survey (SDSS) Stripe 82 field, which has a rich investment of multi-wavelength coverage from the ultraviolet to the radio. The wide-area nature of this survey presents new challenges for photometric redshifts for AGN compared to previous work on narrow-deep fields because it probes different populations of objects that need to be identified and represented in the library of templates. Here we present an updated X-ray plus multi-wavelength matched catalog, including $Spitzer$ counterparts, and estimated photometric redshifts for 5961 (96% of a total of 6181) X-ray sources, which have a normalized median absolute deviation, $\sigma_{\rm nmad}$ = 0.06 and an outlier fraction, $\eta$ = 13.7%. The populations found in this survey, and the template libraries used for photometric redshifts, provide important guiding principles for upcoming large-area surveys such as $eROSITA$ and 3$XMM$ (in X-ray) and the Large Synoptic Survey Telescope (LSST; optical).Comment: Accepted for publication by The Astrophysical Journal (33 pages, 20 figures, 13 tables). Final catalog of counterparts and photo-z supplementing the paper available here: http://stripe82x.com/docs/stripe82x-photometric-redshifts-and-multiwavelength-data-catalog

An Anglo-Saxon execution cemetery at Walkington Wold, Yorkshire

This paper presents a re-evaluation of a cemetery excavated over 30 years ago at Walkington Wold in east Yorkshire. The cemetery is characterized by careless burial on diverse alignments, and by the fact that most of the skeletons did not have associated crania. The cemetery has been variously described as being the result of an early post-Roman massacre, as providing evidence for a ‘Celtic’ head cult or as an Anglo-Saxon execution cemetery. In order to resolve the matter, radiocarbon dates were acquired and a re-examination of the skeletal remains was undertaken. It was confirmed that the cemetery was an Anglo-Saxon execution cemetery, the only known example from northern England, and the site is set into its wider context in the paper

High-throughput allele-specific expression across 250 environmental conditions

Gene-by-environment (GxE) interactions determine common disease risk factors and biomedically relevant complex traits. However, quantifying how the environment modulates genetic effects on human quantitative phenotypes presents unique challenges. Environmental covariates are complex and difficult to measure and control at the organismal level, as found in GWAS and epidemiological studies. An alternative approach focuses on the cellular environment using in vitro treatments as a proxy for the organismal environment. These cellular environments simplify the organism-level environmental exposures to provide a tractable influence on subcellular phenotypes, such as gene expression. Expression quantitative trait loci (eQTL) mapping studies identified GxE interactions in response to drug treatment and pathogen exposure. However, eQTL mapping approaches are infeasible for large-scale analysis of multiple cellular environments. Recently, allele-specific expression (ASE) analysis emerged as a powerful tool to identify GxE interactions in gene expression patterns by exploiting naturally occurring environmental exposures. Here we characterized genetic effects on the transcriptional response to 50 treatments in five cell types. We discovered 1455 genes with ASE (FDR \u3c 10%) and 215 genes with GxE interactions. We demonstrated a major role for GxE interactions in complex traits. Genes with a transcriptional response to environmental perturbations showed sevenfold higher odds of being found in GWAS. Additionally, 105 genes that indicated GxE interactions (49%) were identified by GWAS as associated with complex traits. Examples include GIPR–caffeine interaction and obesity and include LAMP3–selenium interaction and Parkinson disease. Our results demonstrate that comprehensive catalogs of GxE interactions are indispensable to thoroughly annotate genes and bridge epidemiological and genome-wide association studies

Illuminating hydrological processes at the soil-vegetation-atmosphere interface with water stable isotopes

Funded by DFG research project “From Catchments as Organised Systems to Models based on Functional Units” (FOR 1Peer reviewedPublisher PDFPublisher PD