Multiple wheat genomes reveal global variation in modern breeding.

Advances in genomics have expedited the improvement of several agriculturally important crops but similar efforts in wheat (Triticum spp.) have been more challenging. This is largely owing to the size and complexity of the wheat genome1, and the lack of genome-assembly data for multiple wheat lines2,3. Here we generated ten chromosome pseudomolecule and five scaffold assemblies of hexaploid wheat to explore the genomic diversity among wheat lines from global breeding programs. Comparative analysis revealed extensive structural rearrangements, introgressions from wild relatives and differences in gene content resulting from complex breeding histories aimed at improving adaptation to diverse environments, grain yield and quality, and resistance to stresses4,5. We provide examples outlining the utility of these genomes, including a detailed multi-genome-derived nucleotide-binding leucine-rich repeat protein repertoire involved in disease resistance and the characterization of Sm16, a gene associated with insect resistance. These genome assemblies will provide a basis for functional gene discovery and breeding to deliver the next generation of modern wheat cultivars.

People with short symptom duration of knee osteoarthritis benefit more from exercise therapy than people with longer symptom duration: An individual participant data meta-analysis from the OA trial bank.

OBJECTIVE: To investigate whether duration of knee symptoms influenced the magnitude of the effect of exercise therapy compared to non-exercise control interventions on pain and physical function in people with knee osteoarthritis (OA). METHOD: We undertook an individual participant data (IPD) meta-analysis utilising IPD stored within the OA Trial Bank from randomised controlled trials (RCTs) comparing exercise to non-exercise control interventions among people with knee OA. IPD from RCTs were analysed to determine the treatment effect by considering both study-level and individual-level covariates in the multilevel regression model. To estimate the interaction effect (i.e., treatment x duration of symptoms (dichotomised)), on self-reported pain or physical function (standardised to 0-100 scale), a one-stage multilevel regression model was applied. RESULTS: We included IPD from 1767 participants with knee OA from 10 RCTs. Significant interaction effects between the study arm and symptom duration (≤1 year vs >1 year, and ≤2 years vs>2 years) were found for short- (∼3 months) (Mean Difference (MD) -3.57, 95%CI -6.76 to -0.38 and -4.12, 95% CI-6.58 to -1.66, respectively) and long-term (∼12 months) pain outcomes (MD -8.33, 95%CI -12.51 to -4.15 and -8.00, 95%CI -11.21 to -4.80, respectively), and long-term function outcomes (MD -5.46, 95%CI -9.22 to -1.70 and -4.56 95%CI -7.33 to-1.80, respectively). CONCLUSIONS: This IPD meta-analysis demonstrated that people with a relatively short symptom duration benefit more from therapeutic exercise than those with a longer symptom duration. Therefore, there seems to be a window of opportunity to target therapeutic exercise in knee OA.

Successful return to work in anaesthesia after maternity leave: a qualitative study.

Returning to work after maternity leave poses significant challenges, with potential long-term implications including decreased engagement or attrition of clinicians. Many quantitative studies have identified challenges and supports for women during pregnancy, maternity leave and re-entry to clinical practice. This qualitative study explored the experiences of anaesthetists returning to clinical work after maternity leave, to identify influential factors with the aim of providing a framework to assist planning re-entry. We conducted semi-structured interviews with 15 anaesthetists. Attendees of a re-entry programme were invited to participate, with purposive sampling and snowball recruitment to provide diversity of location and training stage, until data saturation was reached at 13 interviews. Five themes were identified: leave duration; planning re-entry; workplace culture; career impact and emotional impact. Leave duration was influenced by concerns about deskilling, but shorter periods of leave had logistical challenges, including fatigue. Most participants started planning to return to work with few or no formal processes in the workplace. Workplace culture, including support for breastfeeding, was identified as valuable, but variable. Participants also experienced negative attitudes on re-entry, including difficulty accessing permanent work, with potential career impacts. Many participants identified changes to professional and personal identity influencing the experience with emotional sequelae. This research describes factors which may be considered to assist clinicians returning to work after maternity leave and identifies challenges, including negative attitudes, which may pose significant barriers to women practising in anaesthesia and may contribute to lack of female leadership in some workplaces.

Still a 'boys' club': a qualitative analysis of how gender affects a career in anaesthesia in Australia and Aotearoa New Zealand.

Gender inequity remains an issue in anaesthesia despite increasing numbers of women training and achieving fellowship in the speciality. Women are under-represented in all areas of anaesthetic research, academia and leadership. The Gender Equity Subcommittee of the Australian and New Zealand College of Anaesthetists recently conducted a survey asking "Does gender still matter in the pursuit of a career in anaesthesia in 2022?". The survey was distributed to a randomly selected sample of 1225 anaesthetic consultants and completed by 470 respondents (38% response rate) with 793 free-text comments provided. Three overarching themes were identified: gender effects on the career and family interface; women do not fit the mould; and gender equity changes the status quo. Women respondents described a need to make a choice between career and family, which was not described by men, as well as stigmatisation of part-time work, a lack of access to challenging work and negative impacts of parental leave. Women respondents also described a sense of marginalisation within anaesthesia due to a 'boys' club' mentality, a lack of professional respect and insufficient structural supports for women in leadership. This was compounded for women from ethnically and culturally diverse backgrounds. A need for specific strategies to support anaesthetic careers for women was described as well as normalisation of flexibility in workplaces, combined with a broadening of our definition of success to allow people of all genders to experience fulfilment both at home and at work. This study is the first published qualitative data on factors affecting gender equity for anaesthetists in Australia and Aotearoa New Zealand. It highlights the need for further exploration, as well providing a foundation for changes in attitude and structural changes towards advancing gender equity.

A family reunion of "clinical cousins": Attachment and emotion in four family-oriented therapy models.

Attachment theory and the science of emotion provide a strong foundation for intervention at the family system level. Four therapeutic models in particular, Attachment-Based Family Therapy, Emotion-Focused Family Therapy, Dyadic Developmental Psychotherapy, and Emotionally Focused Family Therapy, demonstrate how a broad and accurate view of attachment relationships and emotion can be utilized to effectively intervene for a variety of presenting problems in a relational and empathic way for all involved. This paper continues a conversation that began at the Summit for Attachment and Emotion in Family Therapy in 2021 and aims to foster openness, collaboration, and affirmation between four different models of family therapy with shared theoretical roots. The presenters at the Summit and the authors of this paper view similarities across these models as validating and differences as opportunities to serve more families in unique ways, learning from one another's creativity to promote healing within families in the most effective and efficient ways possible. The paper frames the value of attachment theory and emotion science for family therapy, discusses the importance of learning from a variety of models with shared theoretical roots, presents brief summaries of the four models presented at the Summit, compares the models for similarities and complementarities, and shares highlights from each of the presenters from the Summit.

Consistent neutralization of circulating omicron sub-variants by hybrid immunity up to 6 months after booster vaccination.

The current COVID-19 vaccination program requires frequent booster vaccination to maintain sufficient neutralization levels against immune evasive SARS-CoV-2 variants. However, prior studies found more potent and durable immune response in convalescing individuals, raising the possibility of less frequent booster vaccination for them. Here, we conducted a longitudinal immunological study based on two prospective cohorts of booster vaccinated convalescing COVID-19 patients or healthcare workers (HCW) without COVID-19 history in Xiangyang, China. Comparing to 1-month post-boosting, pseudovirus neutralization titers (pVNT50) of ancestral Wuhan-Hu-1 and circulating omicron sub-variants BA.5, BF.7, BA.4.6, BA.2.75, and BA.2.75.2 spikes were stable or even increased in convalescing samples at 6-month post-boosting, when HCW samples showed substantial drop of neutralization titers across the spectrum. Variant-to-Wuhan-Hu-1 pVNT50 ratios showed no significant variation during the 17 months from pre-vaccination to 6-month post-boosting in convalescing individuals, indicating that the high durability of hybrid immunity was likely sustained by continuously improving neutralization potency that compensated immune decay. Our data provide mechanistic insight into prior epidemiological findings that vaccine-elicited humoral immune response was more durable in convalescing individuals than those without SARS-CoV-2 infection, and suggest further research into potential extension of boosting intervals for convalescing individuals.

Factors associated with antibody titer levels among an occupational cohort of fully vaccinated individuals and subsequent risk of COVID-19 infection: A cohort study.

This study (1) determined the association of time since initial vaccine regimen, booster dose receipt, and COVID-19 history with antibody titer, as well as change in titer levels over a defined period, and (2) determined risk of COVID-19 associated with low titer levels. This observational study used data from staff participating in the National Football League COVID-19 Monitoring Program. A cohort of staff consented to antibody-focused sub-study, during which detailed longitudinal data were collected. Among all staff in the program who received antibody testing, COVID-19 incidence following antibody testing was determined. Five hundred eighty-six sub-study participants completed initial antibody testing; 80% (469) completed follow-up testing 50-101 days later. Among 389 individuals who were not boosted at initial testing, the odds of titer < 1000 AU/mL (vs. ≥1000 AU/mL) increased 44% (odds ratio [OR] = 1.44, 95% confidence interval [CI]: 1.18-1.75) for every 30 days since final dose. Among 126 participants boosted before initial testing with no COVID-19 history, 125 (99%) had a value > 2500 AU/ml; 86 (96%) of 90 tested at follow-up and did not develop COVID-19 in the interim remained at that value. One thousand fifty-seven fully vaccinated (330 [29%] boosted at antibody test) individuals participating in the monitoring program were followed to determine COVID-19 status. Individuals with titer value < 1000 AU/mL had twice the risk of COVID-19 as those with >2500 AU/mL (HR = 2.02, 95% CI: 1.28-3.18). Antibody levels decrease postvaccination; boosting increases titer values. While antibody level is not a clear proxy for infection immunity, lower titer values are associated with higher COVID-19 incidence, suggesting increased protection from boosters.

Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative.

OBJECTIVE: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). DESIGN: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7. RESULTS: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. CONCLUSION: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context.

Mycobacterium tuberculosis Inhibitors Based on Arylated Quinoline Carboxylic Acid Backbones with Anti-Mtb Gyrase Activity.

New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating Mycobacterium tuberculosis (Mtb), the causative agent of TB. Thus, the synthesis, characterization, and in vitro screening (MABA and LORA) of 48 QCAs modified with alkyl, aryl, alkoxy, halogens, and nitro groups in the quinoline ring led to the discovery of two QCA derivatives, 7i and 7m, adorned with C-2 2-(naphthalen-2-yl)/C-6 1-butyl and C-2 22-(phenanthren-3-yl)/C-6 isopropyl, respectively, as the best Mtb inhibitors. DNA gyrase inhibition was shown to be exhibited by both, with QCA 7m illustrating better activity up to a 1 µM test concentration. Finally, a docking model for both compounds with Mtb DNA gyrase was developed, and it showed a good correlation with in vitro results.