Ultrafast structured light through nonlinear frequency generation in an optical enhancement cavity.

The generation of shaped laser beams, or structured light, is of interest in a wide range of fields, from microscopy to fundamental physics. There are several ways to make shaped beams, most commonly using spatial light modulators comprised of pixels of liquid crystals. These methods have limitations on the wavelength, pulse duration, and average power that can be used. Here we present a method to generate shaped light that can be used at any wavelength from the UV to IR, on ultrafast pulses, and a large range of optical powers. By exploiting the frequency difference between higher-order modes, a result of the Gouy phase, and cavity mode matching, we can selectively couple into a variety of pure and composite higher-order modes. Optical cavities are used as a spatial filter and then combined with sum-frequency generation in a nonlinear crystal as the output coupler to the cavity to create ultrafast, frequency comb structured light.

At what COST?: A prospective longitudinal cohort assessment of financial toxicity, quality of life, and associated risk factors in patients with plasma cell disorders.

Financial toxicity is prevalent and harmful to patients with plasma cell disorders.

Prevalence of Histological Gastritis in a Community Population and Association with Epigastric Pain.

BACKGROUND AND AIMS: Gastritis is a common histological diagnosis, although the prevalence is decreasing in developed populations, alongside decreasing prevalence of H. pylori infection. We sought to determine the prevalence of the etiology of gastritis in a Swedish population sample and to analyze any associations with symptoms, an area of clinical uncertainty. METHODS: Longitudinal population-based study based in Östhammar, Sweden. A randomly sampled adult population completed a validated gastrointestinal symptom questionnaire (Abdominal Symptom Questionnaire, ASQ) in 2011 (N = 1175). Participants < 80 years of age and who were eligible were invited to undergo esophagogastroduodenoscopy (EGD) (N = 947); 402 accepted and 368 underwent EGD with antral and body biopsies (average 54.1 years, range 20-79 years; 47.8% male) with H. pylori serology. RESULTS: Gastritis was found in 40.2% (148/368; 95% CI 35.2-45.2%). By rank, the most common histological subtype was reactive (68/148; 45.9%), then H. pylori (44/148; 29.7%), chronic non-H. pylori (29/148; 19.6%), and autoimmune (4/148; 2.7%). Gastritis was significantly associated with older age and H. pylori status (p < 0.01). Gastritis subjects were divided into three histological categories: chronic inactive inflammation, autoimmune gastritis, and active inflammation; there was no difference in the presence of upper gastrointestinal symptoms when categories were compared to cases with no pathological changes. Functional dyspepsia or gastroesophageal reflux were reported in 25.7% (38/148) of those with gastritis (any type or location) versus 34.1% (75/220) with no pathological changes (p = 0.32). Epigastric pain was more common in chronic H. pylori negative gastritis in the gastric body (OR = 3.22, 95% CI 1.08-9.62). CONCLUSION: Gastritis is common in the population with a prevalence of 40% and is usually asymptomatic. Chronic body gastritis may be associated with epigastric pain, but independent validation is required to confirm these findings. Clinicians should not generally ascribe symptoms to histological gastritis.

Distinct risk profiles for short-term surgical complications and venous thromboembolism exist among extensor mechanism repair procedures.

PURPOSE: Extensor mechanism injuries, which comprise patella fractures, patella tendon tears and quadriceps tendon tears, are severely debilitating injuries and a common cause of traumatic knee pathology that requires surgical intervention. Risk factors for short-term surgical complications and venous thromboembolism (VTE) in this population have not been well characterised. The aim of this study was to identify perioperative risk factors associated with these short-term complications. METHODS: The National Surgical Quality Improvement Program database was used to identify patients who underwent an isolated, primary extensor mechanism repair from 2015 to 2020. Patients were stratified by injury type. Demographic data were collected and compared. A multivariate logistic regression was used to control for demographic and comorbid factors while assessing risk factors for developing short-term complications. RESULTS: A total of 8355 patients were identified for inclusion in this study. Overall, 3% of patients sustained short-term surgical complications and 1% were diagnosed with VTE within 30 days of surgery. Patella fracture fixation had a nearly twofold higher risk for surgical complications compared to quadriceps tendon repair (p = 0.004). Patella tendon repair had a twofold higher risk for VTE (p = 0.045), specifically deep vein thrombosis (p = 0.020), compared to patella fracture fixation. Increasing age, smoking and American Society of Anesthesiologists Classifications 3 and 4 were also found to be risk factors for surgical complications (p = 0.012, p = 0.004, p = 0.011 and p = 0.032, respectively). CONCLUSION: This study used a nationally representative, widely validated, peer-reviewed database to provide valuable insights into risk factors for short-term postoperative complications associated with extensor mechanism repair procedures, revealing notable differences in risk profiles among distinct surgical procedures. The results of this study will inform surgeons and patients in enhancing risk assessment, guiding procedure-specific decision-making, optimising preoperative care, improving postoperative monitoring and contributing to future research of extensor mechanism injuries. LEVEL OF EVIDENCE: Level III.

Waitlist and Transplant Outcomes in Organ Donation After Circulatory Death: Trends in the United States.

OBJECTIVES: To summarize waitlist and transplant outcomes in kidney, liver, lung, and heart transplantation using organ donation after circulatory death (DCD). BACKGROUND: DCD has expanded the donor pool for solid organ transplantation, most recently for heart transplantation. METHODS: The United Network for Organ Sharing registry was used to identify adult transplant candidates and recipients in the most recent allocation policy eras for kidney, liver, lung, and heart transplantation. Transplant candidates and recipients were grouped by acceptance criteria for DCD versus brain-dead donors [donation after brain death (DBD)] only and DCD versus DBD transplant, respectively. Propensity matching and competing-risks regression was used to model waitlist outcomes. Survival was modeled using propensity matching and Kaplan-Meier and Cox regression analysis. RESULTS: DCD transplant volumes have increased significantly across all organs. Liver candidates listed for DCD organs were more likely to undergo transplantation compared with propensity-matched candidates listed for DBD only, and heart and liver transplant candidates listed for DCD were less likely to experience death or clinical deterioration requiring waitlist inactivation. Propensity-matched DCD recipients demonstrated an increased mortality risk up to 5 years after liver and kidney transplantation and up to 3 years after lung transplantation compared with DBD. There was no difference in 1-year mortality between DCD and DBD heart transplantation. CONCLUSIONS: DCD continues to expand access to transplantation and improves waitlist outcomes for liver and heart transplant candidates. Despite an increased risk for mortality with DCD kidney, liver, and lung transplantation, survival with DCD transplant remains acceptable.

Analysis of Female Participant Representation in Registered Oncology Clinical Trials in the United States from 2008 to 2020.

BACKGROUND: Female underrepresentation in oncology clinical trials can result in outcome disparities. We evaluated female participant representation in US oncology trials by intervention type, cancer site, and funding. MATERIALS AND METHODS: Data were extracted from the publicly available Aggregate Analysis of ClinicalTrials.gov database. Initially, 270,172 studies were identified. Following the exclusion of trials using Medical Subject Heading terms, manual review, those with incomplete status, non-US location, sex-specific organ cancers, or lacking participant sex data, 1650 trials consisting of 240,776 participants remained. The primary outcome was participation to prevalence ratio (PPR): percent females among trial participants divided by percent females in the disease population per US Surveillance, Epidemiology, and End Results Program data. PPRs of 0.8-1.2 reflect proportional female representation. RESULTS: Females represented 46.9% of participants (95% CI, 45.4-48.4); mean PPR for all trials was 0.912. Females were underrepresented in surgical (PPR 0.74) and other invasive (PPR 0.69) oncology trials. Among cancer sites, females were underrepresented in bladder (odds ratio [OR] 0.48, 95% CI 0.26-0.91, P = .02), head/neck (OR 0.44, 95% CI 0.29-0.68, P < .01), stomach (OR 0.40, 95% CI 0.23-0.70, P < .01), and esophageal (OR 0.40 95% CI 0.22-0.74, P < .01) trials. Hematologic (OR 1.78, 95% CI 1.09-1.82, P < .01) and pancreatic (OR 2.18, 95% CI 1.46-3.26, P < .01) trials had higher odds of proportional female representation. Industry-funded trials had greater odds of proportional female representation (OR 1.41, 95% CI 1.09-1.82, P = .01) than US government and academic-funded trials. CONCLUSIONS: Stakeholders should look to hematologic, pancreatic, and industry-funded cancer trials as exemplars of female participant representation and consider female representation when interpreting trial results.

Infectious disease modelling to inform policy.

With modelling becoming increasingly important in helping to inform decisions about animal diseases, it is essential that the process be optimised to gain the maximum benefit for the decision-maker. Here, the authors set out ten steps that can improve this process for all concerned. Four steps describe initialisation to ensure that the question, answer and timescale are defined; two steps describe the modelling process and quality assurance; and four steps describe the reporting stage. The authors believe that this greater emphasis at the beginning and end of a modelling project will increase the relevance of the work and understanding of the results, and thus contribute towards better decision-making.

Compte tenu de l'importance croissante de la modélisation pour documenter les décisions sur les maladies animales, il est essentiel d'optimiser le processus afin de le rendre le plus profitable possible pour les personnes décisionnaires. Les auteurs définissent dix étapes permettant d'améliorer le processus pour tous les intervenants. Quatre étapes concernent la phase de démarrage et visent à s'assurer que les questions posées, les réponses obtenues et le calendrier sont bien définis ; les deux étapes suivantes portent sur le processus de modélisation et sur l'assurance qualité ; les quatre dernières décrivent la phase d'élaboration des rapports. Les auteurs estiment que cette attention particulière accordée aux phases de démarrage et d'achèvement d'un projet de modélisation rend l'exercice plus pertinent et améliore la compréhension des résultats, ce qui contribue à une meilleure prise de décisions.

Dada la creciente importancia que está cobrando la modelización como herramienta para ayudar a fundamentar las decisiones relativas a enfermedades animales, es esencial optimizar el proceso para que las instancias decisorias puedan aprovecharlo al máximo. Los autores exponen diez pasos que pueden mejorar el proceso para cuantos trabajan en este ámbito. En cuatro pasos se describe la inicialización, que sirve para definir debidamente la pregunta, la respuesta y la escala temporal de que se trate. En otros dos pasos se describe el proceso de modelización y de garantía de calidad, mientras que en los últimos cuatro pasos se describe la fase de producción de informes. Los autores consideran que el hecho de otorgar mayor peso a las fases iniciales y finales de un proyecto de modelización hará que el trabajo gane en pertinencia y que se entiendan mejor sus resultados, lo que a su vez contribuye a un proceso más eficaz de adopción de decisiones.

The effect of recreational cannabis legalization and commercialization on substance use, mental health, and injury: a systematic review.

OBJECTIVE: To determine the effect of recreational cannabis legalization (RCL) and/or recreational cannabis commercialization (RCC) on emergency department (ED) visits, hospitalizations, and deaths due to substance use, injury, and mental health among those aged 11 years and older. METHODS: A systematic review of six electronic databases up to February 1, 2023. Original, peer-reviewed articles with interrupted time series or before and after designs were included. Four independent reviewers screened articles and assessed risk of bias. Outcomes with 'critical' risk of bias were excluded. Protocol registered on PROSPERO (# CRD42021265183). RESULTS: After screening and risk of bias assessment, 29 studies were included which examined ED visits or hospitalizations for cannabis use or alcohol (N = 10), opioid mortality (N = 3), motor vehicle fatalities or injury (N = 11), and intentional injury/mental health (N = 5). Rates or number of cannabis-related hospitalizations increased after RCL in Canada and the USA. Immediate increases in rates of cannabis-related ED visits were found after both RCL and RCC in Canada. Rates of traffic fatalities increased after RCL and RCC in certain jurisdictions in the USA. CONCLUSIONS: RCL was associated with increased rates of cannabis-related hospitalizations. RCL and/or RCC was associated with increased rates of cannabis-related ED visits, consistently shown across sex and age groups. The effect on fatal motor vehicle incidents was mixed, with observed increases found after RCL and/or RCC. The effect of RCL or RCC on opioids, alcohol, intentional injury, and mental health is not clear. These results inform population health initiatives and international jurisdictions considering RCL implementation.

Low Rate of Spontaneous Closure in Premature Infants Discharged with a Patent Ductus Arteriosus: A Multicenter Prospective Study.

OBJECTIVES: To assess the rate of spontaneous closure and the incidence of adverse events in infants discharged home with a patent ductus arteriosus. STUDY DESIGN: In a prospective multicenter study, we enrolled 201 premature infants (gestational age of 23-32 weeks at birth) discharged home with a persistently patent ductus arteriosus (PDA) and followed their PDA status at 6-month intervals through 18 months of age. The primary study outcome was the rate and timing of spontaneous ductal closure. Secondary outcomes included rate of assisted closure and the incidence of serious adverse events. RESULTS: Spontaneous ductal closure occurred in 95 infants (47%) at 12 months and 117 infants (58%) by 18 months. Seventeen infants (8.4%) received assisted closure with surgical ligation or device assisted occlusion. Three infants died (1.5%). Although infants with spontaneous closure had a higher mean birth weight and gestational age compared with infants with a persistent PDA or assisted closure, we did not identify other factors predictive of spontaneous closure. CONCLUSIONS: Spontaneous closure of the PDA occurred in slightly less than one-half of premature infants discharged with a patent ductus by 1 year, lower than prior published reports. The high rate of assisted closure and/or adverse events in this population warrants close surveillance following discharge. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02750228.

Root pressure-volume curve traits capture rootstock drought tolerance.

BACKGROUND AND AIMS: Living root tissues significantly constrain plant water uptake under drought, but we lack functional traits to feasibly screen diverse plants for variation in the drought responses of these tissues. Water stress causes roots to lose volume and turgor, which are crucial to root structure, hydraulics and growth. Thus, we hypothesized that root pressure-volume (p-v) curve traits, which quantify the effects of water potential on bulk root turgor and volume, would capture differences in rootstock drought tolerance. METHODS: We used a greenhouse experiment to evaluate relationships between root p-v curve traits and gas exchange, whole-plant hydraulic conductance and biomass under drought for eight grapevine rootstocks that varied widely in drought performance in field trials (101-14, 110R, 420A, 5C, 140-Ru, 1103P, Ramsey and Riparia Gloire), grafted to the same scion variety (Vitis vinifera 'Chardonnay'). KEY RESULTS: The traits varied significantly across rootstocks, and droughted vines significantly reduced root turgor loss point (πtlp), osmotic potential at full hydration (πo) and capacitance (C), indicating that roots became less susceptible to turgor loss and volumetric shrinkage. Rootstocks that retained a greater root volume (i.e. a lower C) also maintained more gas exchange under drought. The rootstocks that previous field trials have classified as drought tolerant exhibited significantly lower πtlp, πo and C values in well-watered conditions, but significantly higher πo and πtlp values under water stress, than the varieties classified as drought sensitive. CONCLUSIONS: These findings suggest that acclimation in root p-v curve traits improves gas exchange in persistently dry conditions, potentially through impacts on root hydraulics or root to shoot chemical signalling. However, retaining turgor and volume in previously unstressed roots, as these roots deplete wet soil to moderately negative water potentials, could be more important to drought performance in the deep, highly heterogenous rooting zones which grapevines develop under field conditions.

Caesarean birth in women with infertility: population-based cohort study.

OBJECTIVE: Caesarean section (CS) is more common following infertility treatment (IT) but the reasons why remain unclear and confounded. The Robson 10-Group Classification System (TGCS) may further explain variation in CS rates. We assessed the association between mode of conception and CS across Robson groups. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, in a public healthcare system. POPULATION: 921 023 births, 2006-2014. METHODS: Modified Poisson regression produced relative risks (RR) and 95% confidence intervals, comparing the risk of CS among women with (1) subfertility without IT, (2) non-invasive IT (OI, IUI) or (3) invasive IT (IVF)-each relative to (4) spontaneous conception (SC). MAIN OUTCOME MEASURES: CS rate according to one of four modes of conception, overall and stratified by each of the TGCS groups. RESULTS: Relative to SC (26.9%), the risk of CS increased in those with subfertility without IT (RR 1.17, 95% CI 1.16-1.18), non-invasive IT (RR 1.21, 95% CI 1.18-1.24) and invasive IT (RR 1.39, 95% CI 1.36-1.42). Within each Robson group, similar patterns of RRs were seen, but with markedly differing rates. For example, in Group 1 (nulliparous, singleton, cephalic at ≥37 weeks, with spontaneous labour), the respective rates were 15.0, 19.4, 18.7 and 21.9%; in Group 2 (nulliparous, singleton, cephalic at ≥37 weeks, without spontaneous labour), the rates were 35.9, 44.4, 43.2 and 54.1%; and in Group 8 (multiple pregnancy), they were 55.9, 67.5, 65.0 and 69.3%, respectively. CONCLUSIONS: CS is relatively more common in women with subfertility and those receiving IT, an effect that persists across Robson groups. TWEETABLE ABSTRACT: Caesarean delivery is more common in women with infertility independent of demographics and prenatal conditions.

Lifestyle improvement reduces the consumption of ultra-processed foods in adults with metabolic syndrome.

BACKGROUND AND AIMS: The high consumption of ultra-processed products is a concern because it is positively associated with the incidence of chronic non-communicable diseases, as metabolic syndrome (MetS). The aim is to evaluate the effects of three different interventions to modify lifestyle on the consumption of ultra-processed foods in adults with MetS. METHODS AND RESULTS: This was a randomized clinical trial, in which the participants were divided into three groups: Standard Intervention (SI), Group Intervention (GI) and Individual Intervention (II). The interventions were carried out over a three-month period and the data was collected in a 24-h food record, taken at the beginning and end of the intervention. The food they ate was classified into four groups according to the degree of processing (unprocessed or minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods) in accordance with the NOVA food classification. Seventy adults took part in the study with a mean age of 51.2 ± 6.6 years old; most of whom were female (55.7%). The amount of ultra-processed food consumed by the three groups (SI, GI and II) was significantly reduced (46%, 34%, and 33%, respectively). The amount of processed food consumed only reduced in the II group. The Total Energy Value (TEV) consumed by the SI and II groups decreased. CONCLUSIONS: The interventions that were intended to alter lifestyles were able to reduce the amount of ultra-processed food consumed, which can have an impact on the prevention and treatment of MetS. REGISTRATION: registered in the Brazilian Registry of Clinical Trials, ReBEC, under number: RBR-9wz5fc.

Factors associated with persistent opioid use 6-12 months after primary total knee arthroplasty.

Persistent pain following knee arthroplasty occurs in up to 20% of patients and may require ongoing analgesia, including extended opioid administration. A comprehensive secondary analysis was performed from results of a study that considered persistent postoperative pain in 242 patients who underwent unilateral knee arthroplasty using a standardised enhanced recovery programme. Opioid prescribing for 12 months before and 12 months after surgery was evaluated and converted to oral morphine equivalents. Demographic, functional, psychological and pain questionnaires were completed along with quantitative sensory testing and genetic analysis. Forty-nine percent of patients had at least one opioid prescription in the 12 months before surgery. Opioid prescriptions were filled in 93% of patients from discharge to 3 months and in 27% of patients ≥6 months after surgery. Persistent opioid use ≥6 months after surgery was strongly associated with pre-operative opioid use (RR 3.2, p < 0.001 (95%CI 1.9-5.4)). The median (IQR [range]) oral morphine equivalent daily dose was 3.6 (0.9-10.5 [0-100.0]) mg pre-operatively, 35.0 (22.5-52.5 [4.6-180.0]) mg in hospital, 12.8 (5.1-24.8 [0-57.9]) mg from discharge to 3 months and 5.9 (4.5-12.0 [0-44.5]) mg at ≥6 months following surgery. Predictors of increased daily oral morphine equivalent ≥6 months after surgery included increased average daily oral morphine equivalent dose compared with previous values (lag), increased body mass index and three or more comorbid pain sites. Persistent opioid use was not associated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (RR 1.003, p = 0.655, 95%CI 0.65-1.002) or WOMAC function (RR 1.001, p = 0.99, 95%CI 0.99-1.03) outcomes 6 months after surgery. There was no association between persistent opioid use and pre-operative quantitative sensory testing results or psychological distress. Pre-operatively, patients with a higher body mass index, more comorbid pain sites and those who had filled an opioid prescription in the last 12 months, were at increased risk of persistent opioid use and a higher oral morphine equivalent daily dose ≥ 6 months after surgery. Strategies need to be developed to limit dose and duration of persistent opioid use in patients following knee arthroplasty surgery.

Risk of thrombosis in women with cancer undergoing controlled ovarian hyperstimulation for fertility preservation.

PURPOSE: The study aims to evaluate the risk factors and incidence of thromboembolic events among adult women with cancer who underwent controlled ovarian hyperstimulation (COH) for fertility preservation. METHODS: Retrospective, descriptive cohort analysis of patient demographics, medical history, cancer type/treatment, laboratory values, thrombosis within 6 months of COH. RESULTS: 4 of 127 study participants experienced a venous thromboembolic event within 6 months of COH. The median time between oocyte aspiration and the event was 0.25 years (range = 0.10-0.50). The average age at time of event was 25.3 years (SD = 5.3). Three of four thrombotic patients had ovarian cancer, one had breast cancer. All had received surgery and chemotherapy for treatment. All underwent an antagonist cycle ovarian stimulation protocol - none developed ovarian hyperstimulation syndrome. The average anti-mullerian hormone level at the time of hyperstimulation in the thrombosis group was 1.6 (SD = 1.3), compared to 3.6 in the non-thrombosis group. The average max estradiol level reached during ovarian stimulation was 1281.3 (SD = 665.3) in the thrombosis group and 1839.1 (SD = 1513.9) in the non-thrombosis group. Thromboembolic events were not directly associated with mortality. CONCLUSIONS: Within this small descriptive study, the incidence of thromboembolic events in women with cancer undergoing COH for fertility preservation is high. Cancer may play a greater role than COH in thrombosis risk. Ovarian cancer patients who undergo ovarian stimulation may have an increased risk compared to other cancer types. These findings may inform future, prospective studies to determine the role of thromboprophylaxis.

Oral vitamin D supplementation induces transcriptomic changes in rectal mucosa that are linked to anti-tumour effects.

BACKGROUND: The risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. METHODS: Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). RESULTS: Six hundred twenty-nine genes were associated with 25-OHD level (P < 0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P < 1.0E-07; downregulated gene-set P < 2.6E-05) and corresponding GO terms (P = 2.90E-02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P < 0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI 0.66-1.00]) and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI 0.77-0.89]; PPP1CC AUC=0.91 [95%CI 0.86-0.95]). CONCLUSIONS: Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects, and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumour transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.

Differences in grapevine rootstock sensitivity and recovery from drought are linked to fine root cortical lacunae and root tip function.

Structural changes during severe drought stress greatly modify the hydraulic properties of fine roots. Yet, the physiological basis behind the restoration of fine root water uptake capacity during water recovery remains unknown. Using neutron radiography (NR), X-ray micro-computed tomography (micro-CT), fluorescence microscopy, and fine root hydraulic conductivity measurements (Lpr ), we examined how drought-induced changes in anatomy and hydraulic properties of contrasting grapevine rootstocks are coupled with fine root growth dynamics during drought and return of soil moisture. Lacunae formation in drought-stressed fine roots was associated with a significant decrease in fine root Lpr for both rootstocks. However, lacunae formation occurred under milder stress in the drought-resistant rootstock, 110R. Suberin was deposited at an earlier developmental stage in fine roots of 101-14Mgt (i.e. drought susceptible), probably limiting cortical lacunae formation during mild stress. During recovery, we found that only 110R fine roots showed rapid re-establishment of elongation and water uptake capacity and we found that soil water status surrounding root tips differed between rootstocks as imaged with NR. These data suggest that drought resistance in grapevine rootstocks is associated with rapid re-establishment of growth and Lpr near the root tip upon re-watering by limiting competing sites along the root cylinder.

Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time: An IMI-DIRECT study.

AIM: To examine the hypothesis that, based on their glucose curves during a seven-point oral glucose tolerance test, people at elevated type 2 diabetes risk can be divided into subgroups with different clinical profiles at baseline and different degrees of subsequent glycaemic deterioration. METHODS: We included 2126 participants at elevated type 2 diabetes risk from the Diabetes Research on Patient Stratification (IMI-DIRECT) study. Latent class trajectory analysis was used to identify subgroups from a seven-point oral glucose tolerance test at baseline and follow-up. Linear models quantified the associations between the subgroups with glycaemic traits at baseline and 18 months. RESULTS: At baseline, we identified four glucose curve subgroups, labelled in order of increasing peak levels as 1-4. Participants in Subgroups 2-4, were more likely to have higher insulin resistance (homeostatic model assessment) and a lower Matsuda index, than those in Subgroup 1. Overall, participants in Subgroups 3 and 4, had higher glycaemic trait values, with the exception of the Matsuda and insulinogenic indices. At 18 months, change in homeostatic model assessment of insulin resistance was higher in Subgroup 4 (ß = 0.36, 95% CI 0.13-0.58), Subgroup 3 (ß = 0.30; 95% CI 0.10-0.50) and Subgroup 2 (ß = 0.18; 95% CI 0.04-0.32), compared to Subgroup 1. The same was observed for C-peptide and insulin. Five subgroups were identified at follow-up, and the majority of participants remained in the same subgroup or progressed to higher peak subgroups after 18 months. CONCLUSIONS: Using data from a frequently sampled oral glucose tolerance test, glucose curve patterns associated with different clinical characteristics and different rates of subsequent glycaemic deterioration can be identified.

The impact of the COVID-19 pandemic on the Ontario Cervical Screening Program, colposcopy and treatment services in Ontario, Canada: a population-based study.

OBJECTIVE: To describe the immediate impact of the COVID-19 pandemic on cervical screening, colposcopy and treatment volumes in Ontario, Canada. DESIGN: Population-based retrospective observational study. SETTING: Ontario, Canada. POPULATION: People with a cervix age of 21-69 years who completed at least one cervical screening cytology test, colposcopy or treatment procedure for cervical dysplasia between January 2019 and August 2020. METHODS: Administrative databases were used to compare cervical screening cytology, colposcopy and treatment procedure volumes before (historical comparator) and during the first 6 months of the COVID-19 pandemic (March-August 2020). MAIN OUTCOME MEASURES: Changes in cervical screening cytology, colposcopy and treatment volumes; individuals with high-grade cytology awaiting colposcopy. RESULTS: During the first 6 months of the COVID-19 pandemic, the monthly average number of cervical screening cytology tests, colposcopies and treatments decreased by 63.8% (range: -92.3 to -41.0%), 39.7% (range: -75.1 to -14.3%) and 31.1% (range: -43.5 to -23.6%), respectively, when compared with the corresponding months in 2019. Between March and August 2020, on average 292 (-51.0%) fewer high-grade cytological abnormalities were detected through screening each month. As of August 2020, 1159 (29.2%) individuals with high-grade screening cytology were awaiting follow-up colposcopy. CONCLUSIONS: The COVID-19 pandemic has had a substantial impact on key cervical screening and follow-up services in Ontario. As the pandemic continues, ongoing monitoring of service utilisation to inform system response and recovery is required. Future efforts to understand the impact of COVID-19-related disruptions on cervical cancer outcomes will be needed. TWEETABLE ABSTRACT: COVID-19 has had a substantial impact on cervical screening and follow-up services in Ontario, Canada.

Vitis Species from the Southwestern United States Vary in Their Susceptibility to Powdery Mildew.

The European grapevine (Vitis vinifera L.) has been cultivated in North America for about 500 years. One of the major limitations to its culture is the powdery mildew (PM) fungus, Erysiphe necator Schw. This study reports on the most extensive screening of Vitis species from the southwestern United States and northern Mexico for resistance to PM, testing 147 accessions of 13 Vitis species. In addition, Vitis vinifera cv. Carignane, a highly susceptible wine grape cultivar, was used as a reference to evaluate the effect of the inoculum 14 days postinoculation. Inoculation was done with a vacuum-operated settling tower using a broadly virulent isolate of E. necator, the C-strain. Resistant accessions (nine), moderately susceptible accessions (39), and highly susceptible accessions (99) were detected. The resistant accessions were then inoculated with an additional fungal isolate, e1-101, and they retained their resistance. Vitis species susceptibility was not associated with a North-South gradation, but Western species were more susceptible than Midwestern and Eastern species. All five of the V. monticola accessions were susceptible, as were the accessions of V. treleasei. The species V. acerifolia, V. candicans, V. cinerea, and V. × doaniana had significantly more resistant to moderately susceptible accessions compared with V. arizonica, V. berlandieri, V. californica, V. × champinii, V. girdiana, V. riparia, and V. rupestris, which had relatively more susceptible accessions than the other species. This research identified new sources of PM resistance in Vitis from the southwestern United States that could be incorporated into PM resistance breeding programs throughout the world.

Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response.

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.