Recommendations for procurement of starting materials by apheresis for advanced therapy medicinal products.

Activities involved in the production of certain advanced therapy medicinal products (ATMPs) require standardized approaches to mononuclear cell procurement to ensure the highest product quality, safety and process efficiency. These aims must be achieved while meeting regulatory and accreditation requirements for the procurement of mononuclear cells as starting materials. Mononuclear cells constitute the starting materials for many ATMPs, and this article sets out recommendations for procurement by clinical apheresis, addressing the variation among existing working practices and different manufacturers' requirements that currently poses a challenge when managing multiple different protocols.

Evaluating the Impact of a Regional Student-Led Physiotherapy Clinic Model to Improve Self-Reported Function in Community-Dwelling Adults With Neurological Diagnoses.

BACKGROUND AND PURPOSE: Neurological conditions are a major cause of health morbidity that negatively impacts function and quality of life (QoL). Despite this burden, community services are disproportionally scarce. Student-led physiotherapy services (SLSs) are a model that can increase community access to health care while providing authentic clinical experiences for students. SLSs consistently demonstrate high client satisfaction; however, limited evaluation of the impact of this model on the client's clinical outcomes exists. Therefore the aim of this project was to evaluate the impact of a physiotherapy student-led community-based rehabilitation service. METHODS: The SLS operated 4 days a week over a 15-week period. Forty-two community-dwelling clients (mean age 74 years) with a neurological diagnosis were included. During initial consultation, participants completed basic demographics, up to 3 Patient-Specific Functional Scales (PSFSs) and a QoL questionnaire (World Health Organization Quality of Life-Brief Questionnaire [WHOQOL-BREF]). At discharge, participants completed the WHOQOL-BREF, PSFS, and a patient experience survey. Risk event data were also collected. RESULTS: Over half of the PSFS items targeted mobility (55%). There was a significant improvement (P < 0.05) in median change (quartiles) for pre-/post-PSFS scores for clients whose primary condition was balance 1.0 (0.0-3.0), cerebrovascular accident 1.0 (2.0-3.0) or multiple Sclerosis 1.0 (1.0-2.0), and mean (SD) WHOQOL-BREF scores for Physical Health (12.2 ± 1.5 to 13.1 ± 1.3) and Social Relationships (12.7 ± 2.7 to 16.6 ± 3.3). Patient experience survey results indicated that clients had confidence and trust in students. No adverse events were reported. DISCUSSION AND CONCLUSIONS: The SLS model provides a strategy to increase access to health care and clinical placement capacity. Findings demonstrated improved self-rated function, QoL, and positive patient experience for community-dwelling clients with nonacute neurological diagnoses.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A380).

Single-molecule DNA sequencing of widely varying GC-content using nucleotide release, capture and detection in microdroplets.

Despite remarkable progress in DNA sequencing technologies there remains a trade-off between short-read platforms, having limited ability to sequence homopolymers, repeated motifs or long-range structural variation, and long-read platforms, which tend to have lower accuracy and/or throughput. Moreover, current methods do not allow direct readout of epigenetic modifications from a single read. With the aim of addressing these limitations, we have developed an optical electrowetting sequencing platform that uses step-wise nucleotide triphosphate (dNTP) release, capture and detection in microdroplets from single DNA molecules. Each microdroplet serves as a reaction vessel that identifies an individual dNTP based on a robust fluorescence signal, with the detection chemistry extended to enable detection of 5-methylcytosine. Our platform uses small reagent volumes and inexpensive equipment, paving the way to cost-effective single-molecule DNA sequencing, capable of handling widely varying GC-bias, and demonstrating direct detection of epigenetic modifications.

Single-molecule detection of deoxyribonucleoside triphosphates in microdroplets.

A new approach to single-molecule DNA sequencing in which dNTPs, released by pyrophosphorolysis from the strand to be sequenced, are captured in microdroplets and read directly could have substantial advantages over current sequence-by-synthesis methods; however, there is no existing method sensitive enough to detect a single nucleotide in a microdroplet. We have developed a method for dNTP detection based on an enzymatic two-stage reaction which produces a robust fluorescent signal that is easy to detect and process. By taking advantage of the inherent specificity of DNA polymerases and ligases, coupled with volume restriction in microdroplets, this method allows us to simultaneously detect the presence of and distinguish between, the four natural dNTPs at the single-molecule level, with negligible cross-talk.

Can you afford to keep practising? Family medicine finances transformed by COVID-19 in Alberta.

OBJECTIVE: To estimate the impact of the coronavirus disease 2019 (COVID-19) pandemic on FP finances in Alberta. DESIGN: A financial model that included fees, visits per day, number of days of practice, and overhead costs. SETTING: Alberta before, during, and after the COVID-19 pandemic. PARTICIPANTS: Hypothetical fee-for-service FP practices. INTERVENTIONS: Changes in practice modes caused by the pandemic and changes to fees set by the Government of Alberta (no interventions were controlled by the researchers). MAIN OUTCOME MEASURES: Annual average FP billings and annual average FP income after overhead expenses. RESULTS: Practice changes related to COVID-19 could result in a reduction in average FP income (billings after expenses) of 27% to 78%. CONCLUSION: Practice pattern changes, including the rapid adoption of telemedicine owing to the COVID-19 pandemic, will reduce incomes for fee-for-service community FP practices in Alberta. Fees at current levels could make some practices unsustainable.

Placing the regionally threatened moss Orthodontium gracile in the big picture - Phylogeny, genome incongruence and anthropogenic dispersal in the order Orthodontiales.

The Orthodontiaceae is a small family of predominantly Southern Hemisphere temperate and South East Asian mosses that has a key phylogenetic position for research into the evolution of pleurocarpy. In the United Kingdom it is represented by the rare conservation priority species Orthodontium gracile and the abundant exotic O. lineare, introduced from the Southern Hemisphere around a century ago. Although the two species are superficially very similar and difficult to tell apart in the field, very little is known about how closely they are related or about the phylogeny, biogeography and evolutionary history of the genus Orthodontium as a whole. Phylogenetic inference and divergence time estimation were used to explore relationships within the genus globally, date major lineage splits, detect reticulate evolutionary processes and test monophyly of taxa. It was shown that Orthodontium gracile belongs to a Holarctic and Asian clade that diverged from the exclusively southern temperate lineage of O. lineare approximately 53 Ma and that it is sister to the Himalayan and South Siberian bispecific genus Orthodontopsis, which we now recognise as a single species within Orthodontium, O. lignicola. Orthodontium lignicola is quite distinct from O. gracile morphologically but may have a closely overlapping centre of extant diversity in the Himalaya, in contrast to O. lineare which is morphologically similar but biogeographically dissimilar. The introduced European populations of Orthodontium lineare were shown to share plastid and nuclear haplotypes with four collections from Tasmania and Southern Chile, but to be distinct from other Chilean and South African haplotypes. Finally, well-supported incongruence between nuclear and plastid sequences in some Western North American populations of Orthodontium gracile strongly implies one or more chloroplast capture or horizontal genome transfer events involving this species and the regionally sympatric O. pellucens. An appeal is made for targeting phylogenetic research at the intersection points of practical conservation, taxonomic uncertainty and wider biological questions and for the factoring of historical evolutionary and phylogenetic diversity into conservation assessments.

Interprofessional collaboration in diabetes care: perceptions of family physicians practicing in or not in a primary health care team.

BACKGROUND: In Canada, most patients with type 2 diabetes mellitus (T2DM) are cared for in the primary care setting in the practices of family physicians. This care is delivered through a variety of practice models ranging from a single practitioner to interprofessional team models of care. This study examined the extent to which family physicians collaborate with other health professionals in the care of patients with T2DM, comparing those who are part of an interprofessional health care team called a Primary Care Network (PCN) to those who are not part of a PCN. METHODS: Family physicians in Alberta, Canada were surveyed to ascertain: which health professionals they refer to or have collaborative arrangements with when caring for T2DM patients; satisfaction and confidence with other professionals' involvement in diabetes care; and perceived effects of having other professionals involved in diabetes care. Chi-squared and Fishers Exact tests were used to test for differences between PCN and non-PCN physicians. RESULTS: 170 (34%) family physicians responded to the survey, of whom 127 were PCN physicians and 41 were non-PCN physicians (2 not recorded). A significantly greater proportion of PCN physicians vs non-PCN physicians referred patients to pharmacists (23.6% vs 2.6%) or had collaborative working arrangements with diabetes educators (55.3% vs 18.4%), dietitians (54.5% vs 21.1%), or pharmacists (43.1% vs 21.1%), respectively. Regardless of PCN status, family physicians expressed greater satisfaction and confidence in specialists than in other family physicians or health professionals in medication management of patients with T2DM. Physicians who were affiliated with a PCN perceived that interprofessional collaboration enabled them to delegate diabetes education and monitoring and/or adjustment of medications to other health professionals and resulted in improved patient care. CONCLUSIONS: This study sheds new insight on the influence that being part of a primary care team has on physicians' practice. Specifically, supporting physicians' access to other health professionals in the primary care setting is perceived to facilitate interprofessional collaboration in the care of patients with T2DM and improve patient care.

Family physicians' perspectives on interprofessional teamwork: Findings from a qualitative study.

The aim of this study was to describe family physicians' perspectives of their role in the primary care team and factors that facilitate and hinder teamwork. A qualitative study was conducted employing individual interviews with 19 academic/community-based family physicians who were part of interprofessional primary care teams in Edmonton, Alberta, Canada. Professional responsibilities and roles of physicians within the team and the facilitators and barriers to teamwork were investigated. Interviews were audiotaped, transcribed and analysed for emerging themes. The study findings revealed that family physicians consistently perceived themselves as having the leadership role on in the primary care team. Facilitators of teamwork included: communication; trust and respect; defined roles/responsibilities of team members; co-location; task shifting to other health professionals; and appropriate payment mechanisms. Barriers to teamwork included: undefined roles/responsibilities; lack of space; frequent staff turnover; network boundaries; and a culture of power and control. The findings suggest that moving family physicians toward more integrative and interdependent functioning within the primary care team will require overcoming the culture of traditional professional roles, addressing facilitators and barriers to teamwork, and providing training in teamwork.

Multiple innovations underpinned branching form diversification in mosses.

Broad-scale evolutionary comparisons have shown that branching forms arose by convergence in vascular plants and bryophytes, but the trajectory of branching form diversification in bryophytes is unclear. Mosses are the most species-rich bryophyte lineage and two sub-groups are circumscribed by alternative reproductive organ placements. In one, reproductive organs form apically, terminating growth of the primary shoot (gametophore) axis. In the other, reproductive organs develop on very short lateral branches. A switch from apical to lateral reproductive organ development is proposed to have primed branching form diversification. Moss gametophores have modular development and each module develops from a single apical cell. Here we define the architectures of 175 mosses by the number of module classes, branching patterns and the pattern in which similar modules repeat. Using ancestral character state reconstruction we identify two stages of architectural diversification. During a first stage there were sequential changes in the module repetition pattern, reproductive organ position, branching pattern and the number of module classes. During a second stage, vegetative changes occurred independently of reproductive fate. The results pinpoint the nature of developmental change priming branching form diversification in mosses and provide a framework for mechanistic studies of architectural diversification.

Imre Festetics and the Sheep Breeders' Society of Moravia: Mendel's Forgotten "Research Network".

Contemporary science thrives on collaborative networks, but these can also be found elsewhere in the history of science in unexpected places. When Mendel turned his attention to inheritance in peas he was not an isolated monk, but rather the latest in a line of Moravian researchers and agriculturalists who had been thinking about inheritance for half a century. Many of the principles of inheritance had already been sketched out by Imre Festetics, a Hungarian sheep breeder active in Brno. Festetics, however, was ultimately hindered by the complex nature of his study traits, aspects of wool quality that we now know to be polygenic. Whether or not Mendel was aware of Festetics's ideas,both men were products of the same vibrant milieu in 19th-century Moravia that combined theory and agricultural practice to eventually uncover the rules of inheritance.