Ariel - Volume 8 Number 2

Executive Editor James W. Lockard , Jr. Issue Editor Doug Hiller Business Manager Neeraj K. Kanwal University News Richard J. Perry World News Doug Hiller Opinions Elizabeth A. McGuire Features Patrick P. Sokas Sports Desk Shahab S. Minassian Managing Editor Edward H. Jasper Managing Associate Brenda Peterson Photography Editor Robert D. Lehman, Jr. Graphics Christine M. Kuhnl

Distinctions Between Self-Report and Performance-Based Measures of Physical Function in Older Patients Prior to Chemotherapy

Under embargo until: 2022-04-02ABSTRACT Background: The maintenance of physical function (PF) is an extremely important outcome for older adults. Objective: The aims of this study were to, identify differences in subjective and objective measures of PF between younger older adults (YOA, 60-69 years of age) and older adults (OA, ≥70 years of age); compare the PF scores with age-matched samples from the general population; and evaluate for associations between subjective and objective measures of PF. Methods: Patients (n=139) were assessed using subjective (i.e., European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (QLQ-C30)) and objective (i.e., Short Physical Performance Battery (SPPB)) measures prior to chemotherapy (CTX). Data were analyzed using parametric and nonparametric tests. Results: No differences were found between the two age groups in any of the subjective or objective measures of PF. Compared to the age-matched general population; both YOA and OA had significantly lower scores in both measures of PF. Large effect sizes were found for differences in QLQ-C30 role function, SPPB balance, and SPPB total scores between the YOA group and the age-matched general population samples. Correlations between the subjective and objective measures were low. Conclusions: Older patients with cancer have lower PF than their age matched general population prior to CTX. Longitudinal studies are warranted to evaluate for changes in PF during and following CTX. Implications for Practice: Nurses need to perform routine assessments of PF in older oncology patients prior to CTX. Our findings suggest that SPPB gait speed may be a useful screening measure for PF in older patients.acceptedVersio

Ginnerup Revisited. New Excavations at a Key Neolithic Site on Djursland, Denmark

New excavations of an enclosure-related site at Ginnerup on Djursland, Denmark, in 2020 resulted in the identification of several features containing depositions of marine shells. One of these, A4, is a natural depression with a fill comprised of four consecutively deposited layers, forming an undisturbed stratigraphy, dated by several 14C dates to between c. 3150 and 2950 BC. The oldest layer contained finds from phase MN A Ib of the Funnel Beaker culture, while the remaining three layers yielded finds from the latest Funnel Beaker culture on Djursland (MN A II/III, Ferslev style) with an upwardly increasing content of Pitted Ware culture elements, thereby allowing the emergence of this culture in Denmark to be followed for the first time. Preservation conditions for organic material were excellent due to a content of marine shells, mainly from oysters and mussels, in all layers. In this preliminary account, a survey of the material culture in the four layers is presented, together with 14C dates, zoological investigations of mammal and fish bones, isotope analyses (d13C, d15N and d34S) and aDNA analyses of mammal bones and examinations of plant macro-remains. The abundant bones of wild horses also hold a huge potential for zoological and genetic studies, the results of which can qualify the ongoing debate about the rewilding of horses in present-day Europe

General practice clinicians’ perspectives on involving and supporting children and adult perpetrators in families experiencing domestic violence and abuse

Background. Government and professional guidance encourages general practice clinicians to identify and refer children who experience domestic violence and abuse (DVA) but there is scant understanding of how general practice clinicians currently work with DVA in families. Objectives. The study explored general practice clinicians’ practice with children and their parents experiencing DVA and reflected on the findings in the light of current research and policy guidelines. Methods. Semi-structured interviews with 54 clinicians (42 GPs and 12 practice nurses/nurse practitioners) were conducted across six sites in England. Data were analysed using current literature and emerging themes. Data presented here concern clinicians’ perspectives on engaging with family members when a parent discloses that she is experiencing DVA. Results. When a parent disclosed DVA, clinicians were more likely to consider talking to abusive fathers than talking to children about the abuse. Perspectives varied according to: whether consultation opportunities arose, risks, consent and confidentiality. Perceptions of ‘patient-hood’, relationships and competence shaped clinicians’ engagement. Perpetrators were seen as competent informers and active service users, with potential for accepting advice and support. Clinicians were more hesitant in talking with children. Where this was considered, children tended to be seen as passive informants, only two GPs described direct and on-going consultations with children and providing them with access to support. Conclusion. Clinicians appear more inclined to engage directly with abusive fathers than children experiencing DVA. Clinician skills and confidence to talk directly with children experiencing DVA, in child sensitive ways, should be developed through appropriate training

A decade of stability for wMel Wolbachia in natural Aedes aegypti populations

Mosquitoes carrying Wolbachia endosymbionts are being released in many countries for arbovirus control. The wMel strain of Wolbachia blocks Aedes-borne virus transmission and can spread throughout mosquito populations by inducing cytoplasmic incompatibility. Aedes aegypti mosquitoes carrying wMel were first released into the field in Cairns, Australia, over a decade ago, and with wider releases have resulted in the near elimination of local dengue transmission. The long-term stability of Wolbachia effects is critical for ongoing disease suppression, requiring tracking of phenotypic and genomic changes in Wolbachia infections following releases. We used a combination of field surveys, phenotypic assessments, and Wolbachia genome sequencing to show that wMel has remained stable in its effects for up to a decade in Australian Ae. aegypti populations. Phenotypic comparisons of wMel-infected and uninfected mosquitoes from near-field and long-term laboratory populations suggest limited changes in the effects of wMel on mosquito fitness. Treating mosquitoes with antibiotics used to cure the wMel infection had limited effects on fitness in the next generation, supporting the use of tetracycline for generating uninfected mosquitoes without off-target effects. wMel has a temporally stable within-host density and continues to induce complete cytoplasmic incompatibility. A comparison of wMel genomes from pre-release (2010) and nine years post-release (2020) populations show few genomic differences and little divergence between release locations, consistent with the lack of phenotypic changes. These results indicate that releases of Wolbachia-infected mosquitoes for population replacement are likely to be effective for many years, but ongoing monitoring remains important to track potential evolutionary changes

Risk factors for peripheral intravenous catheter failure: a multivariate analysis of data from a randomized controlled trial

Objective.To assess the relative importance of independent risk factors for peripheral intravenous catheter (PIVC) failure.Methods.Secondary data analysis from a randomized controlled trial of PIVC dwell time. The Prentice, Williams, and Peterson statistical model was used to identify and compare risk factors for phlebitis, occlusion, and accidental removal.Setting.Three acute care hospitals in Queensland, Australia.Participants.The trial included 3,283 adult medical and surgical patients (5,907 catheters) with a PIVC with greater than 4 days of expected use.Results.Modifiable risk factors for occlusion included hand, antecubital fossa, or upper arm insertion compared with forearm (hazard ratio [HR], 1.47 [95% confidence interval (CI), 1.28--1.68], 1.27 [95% CI, 1.08--1.49], and 1.25 [95% CI, 1.04--1.50], respectively); and for phlebitis, larger diameter PIVC (HR, 1.48 [95% CI, 1.08--2.03]). PIVCs inserted by the operating and radiology suite staff had lower occlusion risk than ward insertions (HR, 0.80 [95% CI, 0.67--0.94]). Modifiable risks for accidental removal included hand or antecubital fossa insertion compared with forearm (HR, 2.45 [95% CI, 1.93--3.10] and 1.65 [95% CI, 1.23--2.22], respectively), clinical staff insertion compared with intravenous service (HR, 1.69 [95% CI, 1.30--2.20]); and smaller PIVC diameter (HR, 1.29 [95% CI, 1.02--1.61]). Female sex was a nonmodifiable factor associated with an increased risk of both phlebitis (HR, 1.64 [95% CI, 1.28--2.09]) and occlusion (HR, 1.44 [95% CI, 1.30--1.61]).Conclusions.PIVC survival is improved by preferential forearm insertion, selection of appropriate PIVC diameter, and insertion by intravenous teams and other specialists.Trial registration.The original randomized controlled trial on which this secondary analysis is based is registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au; ACTRN12608000445370)

Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study

Background & Aims Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. Aims: evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. Methods Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n=48) or placebo (n=46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n=47/48; placebo crossover, n=46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. Results Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. Conclusions Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life

The emergence of Vibrio pathogens in Europe: ecology, evolution, and pathogenesis

Global change has caused a worldwide increase in reports of Vibrio-associated diseases with ecosystem-wide impacts on humans and marine animals. In Europe, higher prevalence of human infections followed regional climatic trends with outbreaks occurring during episodes of unusually warm weather. Similar patterns were also observed in Vibrio-associated diseases affecting marine organisms such as fish, bivalves and corals. Basic knowledge is still lacking on the ecology and evolutionary biology of these bacteria as well as on their virulence mechanisms. Current limitations in experimental systems to study infection and the lack of diagnostic tools still prevent a better understanding of Vibrio emergence. A major challenge is to foster cooperation between fundamental and applied research in order to investigate the consequences of pathogen emergence in natural Vibrio populations and answer federative questions that meet societal needs. Here we report the proceedings of the first European workshop dedicated to these specific goals of the Vibrio research community by connecting current knowledge to societal issues related to ocean health and food security

Functionalized block co-polymer pro-drug nanoparticles with anti-cancer efficacy in 3D spheroids and in an orthotopic triple negative breast cancer model

Amphiphilic block co-polymers composed of poly(ethylene glycol)-co-poly(lactide)-co-poly(2-((tert-butoxycarbonyl)amino)-3-propyl carbonate) (PEG-pLA-pTBPC) are synthesized in monomer ratios and arrangements to enable assembly into nanoparticles with different sizes and architectures. These materials are based on components in clinical use, or known to be biodegradable, and retain the same fundamental chemistry across 'AB' and 'BAB' block architectures. In MCF7 and MDA-MB-231 breast cancer cells, nanoparticles of < 100 nm are internalized most rapidly, by both clathrin-and caveolin-mediated pathways. In THP-1 cells, polymer architecture and length of the hydrophilic block is the most important factor in the rate of internalization. The organ distributions of systemically injected nanoparticles in healthy mice indicate highest accumulation of the BAB-blocks in lungs and liver and the lowest accumulation in these organs of a methoxyPEG5000-pLA-pTBPC polymer. Conjugation of doxorubicin via a serum-stable urea linker to the carbonate regions of PEG5000-pLA-pTBPC generates self-assembling nanoparticles which are more cytotoxic in 2D, and penetrate further in 3D spheroids of triple negative breast cancer cells, than the free drug. In an aggressive orthotopic triple negative breast cancer mouse model, the methoxyPEG5000-pLA-pTBPC is of similar potency to free doxorubicin but with no evidence of adverse effects in terms of body weight