Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children.

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

Development of an Ultrasound Imaging Atlas for Grading Osteoarthritis in the First Metatarsophalangeal Joint.

OBJECTIVE: Ultrasound (US) imaging may play a fundamental role in the earlier detection and assessment of first metatarsophalangeal joint (MTPJ) osteoarthritis (OA) because of its ability to depict tissue-specific morphologic changes before the point of irreversible structural damage. However, the role of US in supporting the diagnosis of OA in foot joints has not been clearly defined. The aims of this study were to develop a semiquantitative US atlas (the AUT ultrasound imaging [AUTUSI] atlas) to grade the degree of osteoarthritic change in the first MTPJ and to evaluate the intraexaminer and interexaminer reproducibility of using the atlas. METHODS: US images were obtained from 57 participants (30 participants with radiographically confirmed first MTPJ OA). The AUTUSI atlas supports the examination of grading joint effusion, synovial hypertrophy, synovitis, osteophytes, joint space narrowing, and cartilage thickness. Six examiners used the atlas to independently grade 24 US images across 2 sessions. Intraexaminer and interexaminer reproducibility were determined using percentage agreement and Gwet's AC2. RESULTS: Observations using the AUTUSI atlas demonstrated almost perfect-to-perfect interexaminer agreement (percentage agreement ranged from 96% to 100%, and Gwet's AC2 values ranged from 0.81 to 1.00) and moderate-to-perfect intraexaminer agreement (percentage agreement ranged from 67% to 100%, and Gwet's AC2 values ranged from 0.54 to 1.00). CONCLUSION: The AUTUSI atlas demonstrated excellent intraexaminer and interexaminer reproducibility for evaluating first MTPJ joint effusion, synovial hypertrophy, synovitis, joint space narrowing, osteophytes, and cartilage thickness. The AUTUSI atlas affords an opportunity to detect prognostic markers of OA earlier in the disease cascade and has the potential to advance understanding of the pathologic process of first MTPJ OA.

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial.

Importance: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy. Objective: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival. Design, Setting, and Participants: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024. Intervention: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery. Main Outcomes and Measures: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy. Results: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13). Conclusions and Relevance: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups. Trial Registration: isrctn.org Identifier: ISRCTN59757862.

Double-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue.

Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across the follicle associated epithelium into the subepithelial dome. The initial response to antigens and how bacteria are handled is incompletely understood. By iterative application of spatial transcriptomics and multiplexed single-cell technologies, we identify that the double negative 2 subset of B cells, previously associated with autoimmune diseases, is present in the subepithelial dome in health. We show that in this location double negative 2 B cells interact with dendritic cells co-expressing the lupus autoantigens DNASE1L3 and C1q and microbicides. We observe that in humans, but not in mice, dendritic cells expressing DNASE1L3 are associated with sampled bacteria but not DNA derived from apoptotic cells. We propose that fundamental features of autoimmune diseases are microbiota-associated, interacting components of normal intestinal immunity.

Reliability of an ultrasound imaging acquisition procedure for examining osteoarthritis in the first metatarsophalangeal joint.

OBJECTIVE: Given the ability of ultrasound imaging (USI) to depict tissue-specific morphological changes before the onset of pain and before the point of irreversible structural damage, USI could play a fundamental role in earlier detection and assessment of foot osteoarthritis (OA). The current guidelines require further refinement of anatomical landmarks to establish a standardized imaging procedure to improve the interpretability and reproducibility between studies evaluating the first metatarsophalangeal joint (MTPJ). The aims were to develop an USI acquisition procedure and grading system to examine OA features in the first MTPJ and to determine intra-examiner and inter-examiner reliability of a newly developed USI acquisition procedure. DESIGN: Thirty participants with first MTPJ OA confirmed radiographically with the use of the La Trobe Foot Atlas were included. An experienced sonographer applied a newly developed USI procedure to examine the following features: joint effusion, synovial hypertrophy, synovitis, joint space narrowing, osteophytes, and cartilage thickness. A semiquantitative grading system was applied to all features. A continuous measure was also examined for osteophyte size, joint space narrowing, and cartilage thickness. To determine the intra-examiner and inter-examiner reliability, an experienced radiologist and sonographer applied the developed grading system to the images acquired from two imaging sessions. Intra-examiner and inter-examiner reliability were calculated using intraclass correlation coefficients (ICCs). RESULTS: ICCs for intra-examiner between session reliability ranged from 0.58 to 0.92 for semiquantitative grading and 0.39 to 0.94 for continuous measures. Joint effusion and osteophytes achieved the highest intra-examiner reliability (ICC = 0.78-0.94). ICCs for session one inter-examiner reliability ranged from 0.61 to 1.0 for semiquantitative grading; all continuous measures had an ICC of 1. ICCs for session two inter-examiner reliability ranged from 0.55 to 1.0 for semiquantitative grading and 0.9 to 0.97 for continuous measures. Inter-examiner reliability was good for grading joint effusion (ICC = 0.55-0.62) and was excellent for all other USI features (ICC = 0.77-1.0). CONCLUSION: The USI acquisition procedure and grading system are reliable in evaluating first MTPJ OA features in participants with radiologically confirmed OA. The study will inform the methodological development of an ultrasound atlas for grading the degree of osteoarthritic change in the first MTPJ.

Breast Cancer Method of Detection: 5-Year Outcomes Across a Multisite Health Care Enterprise.

PURPOSE: To investigate the feasibility and accuracy of radiologists categorizing the method of detection (MOD) when performing image-guided breast biopsies. METHODS: This retrospective, observational study was conducted across a health care enterprise that provides breast imaging services at 18 imaging sites across four US states. Radiologists used standardized templates to categorize the MOD, defined as the first test, sign, or symptom that triggered the subsequent workup and recommendation for biopsy. All image-guided breast biopsies since the implementation of the MOD-inclusive standardized template-from October 31, 2017 to July 6, 2023-were extracted. A random sample of biopsy reports was manually reviewed to evaluate the accuracy of MOD categorization. RESULTS: A total of 29,999 biopsies were analyzed. MOD was reported in 29,423 biopsies (98.1%) at a sustained rate that improved over time. The 10 MOD categories in this study included the following: 15,184 mammograms (51.6%); 4,561 MRIs (15.5%); 3,473 ultrasounds (11.8%); 2,382 self-examinations (8.1%); 2,073 tomosynthesis studies (7.0%); 432 clinical examinations (1.5%); 421 molecular breast imaging studies (1.4%); 357 other studies (1.2%); 338 contrast-enhanced digital mammograms (1.1%); and 202 PET studies (0.7%). Original assignments of the MOD agreed with author assignments in 87% of manually reviewed biopsies (n = 100, 95% confidence interval: [80.4%, 93.6%]). CONCLUSIONS: This study demonstrates that US radiologists can consistently and accurately categorize the MOD over an extended time across a health care enterprise.

Genetic and immune landscape evolution in MMR-deficient colorectal cancer.

Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD-L1) immunostaining to systematically investigate ITH and how genetic and immune landscapes coevolve. All cases had high truncal mutation burdens. Despite pervasive ITH, driver aberrations showed a clear hierarchy. Those in WNT/ß-catenin, mitogen-activated protein kinase, and TGF-ß receptor family genes were almost always truncal. Immune evasion (IE) drivers, such as inactivation of genes involved in antigen presentation or IFN-γ signalling, were predominantly subclonal and showed parallel evolution. These IE drivers have been implicated in immune checkpoint inhibitor resistance or sensitivity. Clonality assessments are therefore important for the development of predictive immunotherapy biomarkers in MMRd CRCs. Phylogenetic analysis identified three distinct patterns of IE driver evolution: pan-tumour evolution, subclonal evolution, and evolutionary stasis. These, but neither mutation burdens nor heterogeneity metrics, significantly correlated with T-cell densities, which were used as a surrogate marker of tumour immunogenicity. Furthermore, this revealed that genetic and T-cell infiltrates coevolve in MMRd CRCs. Low T-cell densities in the subgroup without any known IE drivers may indicate an, as yet unknown, IE mechanism. PD-L1 was expressed in the tumour microenvironment in most samples and correlated with T-cell densities. However, PD-L1 expression in cancer cells was independent of T-cell densities but strongly associated with loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and may contribute to a higher recurrence risk of MMRd CRCs with impaired CDX2 expression. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Pasteurella sp. associated with fatal septicaemia in six African elephants.

The sudden mortality of African elephants (Loxodonta africana) in Botswana and Zimbabwe in 2020 provoked considerable public interest and speculation. Poaching and malicious poisoning were excluded early on in the investigation. Other potential causes included environmental intoxication, infectious diseases, and increased habitat stress due to ongoing drought. Here we show evidence of the mortalities in Zimbabwe as fatal septicaemia associated with Bisgaard taxon 45, an unnamed close relative of Pasteurella multocida. We analyse elephant carcasses and environmental samples, and fail to find evidence of cyanobacterial or other intoxication. Post-mortem and histological findings suggest a bacterial septicaemia similar to haemorrhagic septicaemia caused by P. multocida. Biochemical tests and 16S rDNA analysis of six samples and genomic analysis of one sample confirm the presence of Bisgaard taxon 45. The genome sequence contains many of the canonical P. multocida virulence factors associated with a range of human and animal diseases, including the pmHAS gene for hyaluronidase associated with bovine haemorrhagic septicaemia. Our results demonstrate that Bisgaard taxon 45 is associated with a generalised, lethal infection and that African elephants are susceptible to opportunistically pathogenic Pasteurella species. This represents an important conservation concern for elephants in the largest remaining metapopulation of this endangered species.

Comparison of the relative impacts of acute consumption of an inulin-enriched diet, milk kefir or a commercial probiotic product on the human gut microbiome and metabolome.

It has been established that the human gut microbiota is central to health, and, consequently, there has been a growing desire to positively modulate its composition and/or function through, for example, the use of fermented foods, prebiotics or probiotics. Here, we compare the relative impact of the daily consumption of an inulin-enriched diet (n = 10), a commercial probiotic-containing fermented milk product (FMP) (n = 10), or a traditional kefir FMP (n = 9), over a 28-day period on the gut microbiome and urine metabolome of healthy human adults. None of the treatments resulted in significant changes to clinical parameters or biomarkers tested. However, shotgun metagenomic analysis revealed that kefir consumption resulted in a significant change in taxonomy, in the form of an increased abundance of the sub-dominant FMP-associated species Lactococcus raffinolactis, which further corresponded to shifts in the urine metabolome. Overall, our results indicated that daily consumption of a single portion of kefir alone resulted in detectable changes to the gut microbiota and metabolome of consumers.

Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma.

Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast-activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD8+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD8+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.

Exploring the current and future osteoarthritis health service delivery needs in Aotearoa New Zealand.

AIM: Osteoarthritis (OA) affects the wellbeing of one in 10 people in Aotearoa New Zealand, yet current healthcare delivery for these people is fragmented, un-coordinated and inconsistent. How current and future needs should be addressed has not been systematically explored. This study aimed to describe the views of interested people from the health sector regarding current and future OA health service delivery in the public health system in Aotearoa New Zealand. METHOD: Data were collected via a co-design approach within an interprofessional workshop at the Taupuni Hao Huatau Kaikoiwi: Osteoarthritis Aotearoa New Zealand Basecamp symposium and analysed using direct qualitative content analysis. RESULTS: The results highlighted several promising current healthcare delivery initiatives. Health literacy and obesity prevention policies featured in the thematic analysis suggesting a lifespan or systemwide approach is needed. Data highlighted a need for reformed systems that enhances hauora/wellbeing, promotes physical activity, facilitates interprofessional service delivery and collaborates across care settings. CONCLUSION: Participants identified several promising healthcare delivery initiatives for people with OA in Aotearoa New Zealand. Public health policy initiatives are needed to reduce osteoarthritis risk factors. Developing future care pathways should support the diverse needs within Aotearoa New Zealand, coordinate and stratify care, value interprofessional collaboration and practice, and improve health literacy and self-management.

SCOT: Tumor Sidedness and the Influence of Adjuvant Chemotherapy Duration on Disease Free Survival (DFS).

AIM: Patients with loco-regional right-sided colorectal tumors have a worse overall survival (OS). Here we investigate the difference in disease free survival (DFS) between colorectal patients with right and left sided tumors in the SCOT study. METHODS: The SCOT study showed 3-months of oxaliplatin-containing adjuvant chemotherapy (OxFp) is non-inferior to 6-months for patients with stage III and high-risk stage II colorectal cancer. We divided the cohort into patients with left and right sided tumors, and evaluated the effect on DFS and the principle 3 versus 6-months analysis. RESULTS: 6088 patients with Stage III/high risk Stage II colorectal cancers were randomized between 27th March 2008 and 29th November 2013 from 244 centers internationally. In February 2017 (3-years FU) information on sidedness was available for 3309 patients (1238 R-sided, 2071 L-sided). Patients with right-sided tumors had a significantly worse DFS (3-year DFS right: 73.3% (se = 1.3%), left: 80.2% (se = 0.9%) HR 1.423 (95% CI 1.237-1.637; P < .0001). Adjusting for T and N-stage reduced the HR to 1.230 (95% CI 1.066-1.420, P = .005). The data did not suggest that sidedness affected the impact of chemotherapy duration on 3-year DFS (R: HR 1.024 [0.831-1.261], L: HR 0.944 [0.783-1.139]). Test for heterogeneity, P = .571. Further sub-set analysis was limited due to cohort size. CONCLUSIONS: This is the first study to show that unselected patients with right-sided tumors had a worse DFS compared to left-sided tumors. Tumor sidedness did not impact upon the 3-months versus 6-months comparison in SCOT.

Validity and Reliability of 3-D Ultrasound Imaging to Measure Hamstring Muscle and Tendon Volumes.

OBJECTIVE: The validity and reliability of 3-D ultrasound (US) in estimation of muscle and tendon volume was assessed in a very limited number of muscles that can be easily immersed. The objective of the present study was to assess the validity and reliability of muscle volume measurements for all hamstring muscle heads and gracilis (GR), as well as tendon volume for the semitendinosus (ST) and GR using freehand 3-D US. METHODS: Three-dimensional US acquisitions were performed for 13 participants in two distinct sessions on separate days, in addition to one session dedicated to magnetic resonance imaging (MRI). Volumes of ST, semimembranosus (SM), biceps femoris short (BFsh) and long (BFlh) heads, and GR muscles and from the tendon from semitendinosus (STtd) and gracilis (GRtd) were collected. RESULTS: The bias and the 95% confidence intervals of 3-D US compared with MRI ranged from -1.9 mL (-0.8%) to 1.2 mL (1.0%) for muscle volume and from 0.01 mL (0.2%) to -0.03 mL (-2.6%) for tendon volume. For muscle volume assessed using 3-D US, intraclass correlation coefficients (ICCs) ranged from 0.98 (GR) to 1.00, and coefficients of variation (CV) from 1.1% (SM) to 3.4% (BFsh). For tendon volume, ICCs were 0.99, and CVs between 3.2% (STtd) and 3.4% (GRtd). CONCLUSION: Three-dimensional US can provide a valid and reliable inter-day measurement of hamstrings and GR for both muscle and tendon volumes. In the future, this technique could be used as an outcome for strengthening interventions and potentially in clinical environments.

International multispecialty consensus on how to image, define, and grade ultrasound imaging features of first metatarsophalangeal joint osteoarthritis, a Delphi consensus study.

Objective: To reach consensus concerning which ultrasound imaging features should be assessed and graded, and what ultrasound imaging procedure should be performed when examining osteoarthritic change in the first metatarsophalangeal joint. Design: An online Delphi study was conducted over four iterative rounds with 16 expert health professionals. Items were scored from 0 to 100 (0 â€‹= â€‹not at all important; 100 â€‹= â€‹extremely important). Consensus was defined based upon an item receiving a median score of ≥70% acceptance. Items receiving median score of ≤50% were rejected. Items considered ambiguous (median score 51%-69% of acceptance) were assessed in an additional round. A final round determined the content validity of items through calculation of the content validity ratio and content validity index. Results: Sixteen items were deemed essential, which included osteophytes graded dichotomously, cartilage damage graded continuously, synovitis and joint space narrowing graded on a semiquantitative scale. The panel deemed essential that the first metatarsophalangeal joint start in a neutral position, then move through range of motion for both dorsal and plantar scanning, orientating the probe in longitudinal and in transverse, whilst using first metatarsal head and proximal phalanx as anatomical landmarks. A supine body position was only deemed essential for a dorsal scan and a neutral foot/ankle position was only rated essential for a plantar scan. The content validity index of the 16 essential items was 0.19. Conclusion: The consensus exercise has identified the essential components the ultrasound imaging acquisition procedure should encompass when examining first metatarsophalangeal joint osteoarthritis.

The effect of Tubigrip and a rigid belt on rectus abdominus diastasis immediately postpartum: A randomised clinical trial.

BACKGROUND: Rectus abdominis (RA) diastasis is a risk factor for abdominal muscle dysfunction and reduced quality of life postpartum. It is thought that supplementary abdominal supports might reduce the diastasis. However, there is limited research assessing the efficacy of abdominal supports/binding. OBJECTIVE: To determine the effects of Tubigrip and a rigid abdominal belt in reducing RA diastasis in the first eight weeks postpartum. DESIGN: Randomised clinical trial. METHODS: 62 women undertook ultrasound imaging to measure their RA diastasis prior to and after an eight week intervention wearing either Tubigrip or a rigid abdominal belt. Data analyses involved repeated measures ANOVA and correlational methods. RESULTS: The RA diastasis reduced by 46% from a mean 4.6 cm-2.5 cm over the eight week intervention period with no significant difference (p > 0.05) across groups. Women wore the Tubigrip for a significantly (p < 0.05) longer number of hours (Median: 278) compared to those in the belt group (Median: 81 h). The length of time that women wore Tubigrip or the belt was not associated with the percentage reduction in the RA diastasis (p > 0.05). There was no significant difference in the diastasis across vaginal and Caesarean section deliveries at baseline. There was a significant difference (p < 0.05) in the percent reduction of the RA diastasis across deliveries post-intervention (vaginal delivery mean: 48% vs C-section: 40%). CONCLUSION: There was no difference across groups post-intervention in the RA diastasis, and it is questionable whether either support improves upon that associated with natural healing alone.

Mechanical Effects of a Specific Neurodynamic Mobilization of the Superficial Fibular Nerve: A Cadaveric Study.

CONTEXT: A specific neurodynamic mobilization for the superficial fibular nerve (SFN) has been suggested in the reference literature for manual therapists to evaluate nerve mechanosensitivity in patients. However, no authors of biomechanical studies have examined the ability of this technique to produce nerve strain. Therefore, the mechanical specificity of this technique is not yet established. OBJECTIVES: To test whether this examination and treatment technique produced nerve strain in the fresh frozen cadaver and the contribution of each motion to total longitudinal strain. DESIGN: Controlled laboratory study. SETTING: Laboratory. MAIN OUTCOME MEASURE(S): A differential variable reluctance transducer was inserted in 10 SFNs from 6 fresh cadavers to measure strain during the mobilization. A specific sequence of plantar flexion, ankle inversion, straight-leg raise position, and 30° of hip adduction was applied to the lower limb. The mobilization was repeated at 0°, 30°, 60°, and 90° of the straight-leg raise position to measure the effect of hip-flexion position. RESULTS: Compared with a resting position, this neurodynamic mobilization produced a significant amount of strain in the SFN (7.93% ± 0.51%, P < .001). Plantar flexion (59.34% ± 25.82%) and ankle inversion (32.80% ± 21.41%) accounted for the biggest proportions of total strain during the mobilization. No difference was noted among different hip-flexion positions. Hip adduction did not significantly contribute to final strain (0.39% ± 10.42%, P > .05), although high variability among limbs existed. CONCLUSIONS: Ankle motion should be considered the most important factor during neurodynamic assessment of the SFN for distal entrapment. These results suggest that this technique produces sufficient strain in the SFN and could therefore be evaluated in vivo for correlation with mechanosensitivity.

Randomized controlled trial of EndoRings assisted colonoscopy versus standard colonoscopy.

OBJECTIVES: The EndoRings device is a distal attachment consisting of two layers of circular flexible rings that evert mucosal folds. The aim of this study was to investigate whether EndoRing assisted colonoscopy (ER) improves polyp and adenoma detection compared to standard colonoscopy (SC). METHODS: Multicenter, parallel group, randomized controlled trial. RESULTS: Total of 556 patients randomized to ER (n = 275) or SC (n = 281). Colonoscopy completed in 532/556 (96%) cases. EndoRings removed in 74/275 (27%) patients. Total number of polyps in ER limb 582 vs. 515 in SC limb, P = 0.04. Total number of adenomas in ER limb 361 vs. 343 for SC limb, P = 0.49. A statistically significant difference in the mean number of polyps per patient in both the intention to treat (1.84 SC vs. 2.10 ER, P = 0.027) and per protocol (PP) (1.84 SC vs. 2.25 ER, P = 0.004). CONCLUSIONS: Our study shows promise for the EndoRings device to improve polyp detection.

Nocturnal plant respiration is under strong non-temperature control.

Most biological rates depend on the rate of respiration. Temperature variation is typically considered the main driver of daily plant respiration rates, assuming a constant daily respiration rate at a set temperature. Here, we show empirical data from 31 species from temperate and tropical biomes to demonstrate that the rate of plant respiration at a constant temperature decreases monotonically with time through the night, on average by 25% after 8 h of darkness. Temperature controls less than half of the total nocturnal variation in respiration. A new universal formulation is developed to model and understand nocturnal plant respiration, combining the nocturnal decrease in the rate of plant respiration at constant temperature with the decrease in plant respiration according to the temperature sensitivity. Application of the new formulation shows a global reduction of 4.5 -6 % in plant respiration and an increase of 7-10% in net primary production for the present-day.

A heteroskedastic model of Park Grass spring hay yields in response to weather suggests continuing yield decline with climate change in future decades.

UK grasslands perform important environmental and economic functions, but their future productivity under climate change is uncertain. Spring hay yields from 1902 to 2016 at one site (the Park Grass Long Term Experiment) in southern England under four different fertilizer regimes were modelled in response to weather (seasonal temperature and rainfall). The modelling approach applied comprised: (1) a Bayesian model comparison to model parametrically the heteroskedasticity in a gamma likelihood function; (2) a Bayesian varying intercept multiple regression model with an autoregressive lag one process (to incorporate the effect of productivity in the previous year) of the response of hay yield to weather from 1902 to 2016. The model confirmed that warmer and drier years, specifically, autumn, winter and spring, in the twentieth and twenty-first centuries reduced yield. The model was applied to forecast future spring hay yields at Park Grass under different climate change scenarios (HadGEM2 and GISS RCP 4.5 and 8.5). This application indicated that yields are forecast to decline further between 2020 and 2080, by as much as 48-50%. These projections are specific to Park Grass, but implied a severe reduction in grassland productivity in southern England with climate change during the twenty-first century.