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Objectives: Lenalidomide combined with rituximab (R2) has shown complimentary clinical activity and is a tolerable regimen in both untreated and relapsed or refractory (R/R) patients (pts) with indolent non-Hodgkin lymphoma. Pts with advanced age at diagnosis are considered to be high risk, supporting post-hoc subgroup analyses by age, with a focus on pts aged ≥ 70 years from the MAGNIFY study. Materials and methods: MAGNIFY is a multicenter, phase 3b trial (NCT01996865) in pts with R/R follicular lymphoma (FL) grades 1–3b, transformed FL (tFL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL). Lenalidomide 20 mg on d 1–21 of a 28-d cycle + rituximab 375 mg/m2/wk cycle 1 and then every 8 wk starting with cycle 3 (R2) is given for 12 cycles followed by 1:1 randomization in pts with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 vs rituximab maintenance for 18 mo. The primary end point is progression-free survival (PFS) by 1999 International Working Group (IWG) criteria. Secondary end points include safety, CR rate, duration of response DOR, duration of CR DOCR, time-to-response TTR, time-to-next antilymphoma therapy, and overall survival. Data presented here focus on induction R2 in efficacy-evaluable FL grade 1–3a and MZL pts (FL grade 3b, tFL, and MCL not included) receiving ≥ 1 treatment with baseline/postbaseline assessments. Post-hoc analyses were performed by analyzing data from pts aged ≥ 70 years at time of study entry. Results: As of August 28, 2020, 394 pts have enrolled and 152 (39%) were aged ≥ 70 years. Baseline characteristics including histology, disease status, and prior treatments of pts ≥ 70 and the overall population were similar. Median PFS in the ≥ 70 subgroup was 40.1 months (95% CI, 28.6–NR). Overall response rate (ORR) and CR/CRu were 75% and 39%, with a median duration of response that was not reached (95% CI, 29.4–NR). Efficacy results for the overall population were similar; median PFS = 41.2 mo (95% CI, 38.7–NR), ORR = 75%, CR = 44%, and median DOR = NR (95% CI, 38.6–NR). In pts ≥ 70 the most common (≥ 20%) any-grade treatment emergent adverse events (TEAEs) were fatigue (44%), neutropenia (41%), diarrhea (34%), constipation (34%), and nausea (27%). Neutropenia (35%) was the only grade 3/4 TEAE occurring in > 10% of pts (febrile neutropenia occurred in 3 pts [2%]). TEAEs led to lenalidomide dose reduction in 71 pts (47%) and discontinuation in 42 pts (28%). Eighty-two pts ≥ 70 (54%) completed all 12 cycles of induction treatment, and 75 (49%) have entered the maintenance phase. Sixty-two pts ≥ 70 (41%), prematurely discontinued both lenalidomide and rituximab, due to TEAEs (n = 28; 18%), progressive disease (n = 14; 9%), patient withdrawal (n = 12; 8%), death (n = 4; 3%), and other reasons (n = 4; 3%). Neutropenia was the only TEAE leading to discontinuation of lenalidomide in more than 2 pts (n = 10; 7%). Discussion: Similar to findings in the overall population, R2 treatment in advanced-age pts with R/R FL and MZL resulted in encouraging efficacy, and with close attention to dose reduction there is a tolerable safety profile. Conclusions: These results suggest that R2 should be considered as a therapeutic option for advanced-age pts with R/R FL and MZL.

Objectives: Relapse is expected when treating patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL), with a shortened response associated with each relapse. Lenalidomide combined with rituximab (R2) has shown enhanced activity, with a recently reported median progression free-survival (PFS) of 39.4 months in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma, including those with FL and MZL (Augment; J Clin Oncol. 2019;37:1188). Materials and methods: MAGNIFY is a multicenter, phase 3b trial (NCT01996865) in patients with R/R follicular lymphoma (FL) grades 1–3b, transformed FL (tFL), MZL, and mantle cell lymphoma (MCL). Lenalidomide 20 mg on d 1–21 of a 28-d cycle + rituximab 375 mg/m2/wk cycle 1 and then every 8 wk starting with cycle 3 (R2) is given for 12 cycles followed by 1:1 randomization in patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 vs rituximab maintenance for 18 mo. The primary end point is progression-free survival (PFS) by 1999 International Working Group criteria. Secondary end points include safety, CR rate, duration of response (DOR), duration of CR, time-to-response, time-to-next antilymphoma therapy, and overall survival. Data presented here focus on induction R2 in efficacy-evaluable patients with MZL compared with the overall population of FL grades 1–3a+MZL (not including FL grade 3b, tFL, or MCL) receiving ≥ 1 treatment with baseline/post-baseline assessments. Results: As of August 28, 2020, 394 patients with FL grades 1–3a and MZL enrolled; 76 (19%) had MZL. The median age of patients with MZL was 68 years (range, 46–90), 68 (89%) had stage III/IV disease, and 72 (95%) had prior rituximab-containing therapy. Overall response rate in the MZL and overall population was 66% and 75% with 39% and 44% having a CR/CRu. Median DOR was 38.6 months (95% CI, 29.4–not reached [NR]) and NR (95% CI, 38.6–NR). The median PFS was 40.9 months (95% CI, 27.8–NR) and 41.2 months (95% CI, 38.7–NR). In the MZL population, 43 patients (57%) have completed 12 cycles of R2, and 42 (55%) have been randomized and entered maintenance. Twenty-eight patients (37%) prematurely discontinued both lenalidomide and rituximab, primarily due to adverse events (AEs; n = 11; 14%) and progressive disease (n = 6; 8%). The most common (≥ 20%) all-grade AEs were neutropenia (49%), fatigue (43%), diarrhea (37%), thrombocytopenia (24%), constipation (24%), and anemia (22%). Most common (≥ 10%) grade 3/4 AEs were neutropenia (41%; 1 patient [1%] had febrile neutropenia), thrombocytopenia (13%), and leukopenia (13%). Discussion: R2 is active with a tolerable safety profile in patients with R/R MZL. The efficacy and safety profile of R2 in patient with MZL were similar to results observed in the overall MAGNIFY population. Conclusions: These results suggest that R2 should be considered as a therapeutic option for patients with R/R MZL.

ABSTRACT: Automated measurements of the ratio of concentrations of methane and carbon dioxide, [CH4]:[CO2], in breath from individual animals (the so-called “sniffer technique”) and estimated CO2 production can be used to estimate CH4 production, provided that CO2 production can be reliably calculated. This would allow CH4 production from individual cows to be estimated in large cohorts of cows, whereby ranking of cows according to their CH4 production might become possible and their values could be used for breeding of low CH4-emitting animals. Estimates of CO2 production are typically based on predictions of heat production, which can be calculated from body weight (BW), energy-corrected milk yield, and days of pregnancy. The objectives of the present study were to develop predictions of CO2 production directly from milk production, dietary, and animal variables, and furthermore to develop different models to be used for different scenarios, depending on available data. An international dataset with 2,244 records from individual lactating cows including CO2 production and associated traits, as dry matter intake (DMI), diet composition, BW, milk production and composition, days in milk, and days pregnant, was compiled to constitute the training dataset. Research location and experiment nested within research location were included as random intercepts. The method of CO2 production measurement (respiration chamber [RC] or GreenFeed [GF]) was confounded with research location, and therefore excluded from the model. In total, 3 models were developed based on the current training dataset: model 1 (“best model”), where all significant traits were included; model 2 (“on-farm model”), where DMI was excluded; and model 3 (“reduced on-farm model”), where both DMI and BW were excluded. Evaluation on test dat sets with either RC data (n = 103), GF data without additives (n = 478), or GF data only including observations where nitrate, 3-nitrooxypropanol (3-NOP), or a combination of nitrate and 3-NOP were fed to the cows (GF+: n = 295), showed good precision of the 3 models, illustrated by low slope bias both in absolute values (−0.22 to 0.097) and in percentage (0.049 to 4.89) of mean square error (MSE). However, the mean bias (MB) indicated systematic overprediction and underprediction of CO2 production when the models were evaluated on the GF and the RC test datasets, respectively. To address this bias, the 3 models were evaluated on a modified test dataset, where the CO2 production (g/d) was adjusted by subtracting (where measurements were obtained by RC) or adding absolute MB (where measurements were obtained by GF) from evaluation of the specific model on RC, GF, and GF+ test datasets. With this modification, the absolute values of MB and MB as percentage of MSE became negligible. In conclusion, the 3 models were precise in predicting CO2 production from lactating dairy cows.

The protective nature of adequate sleep during adolescence is poorly understood, particularly regarding social relationships. We explored emotion and behaviour during two social interaction tasks among teens assigned to sleep extension (SE) or typical sleep (TS) conditions. Twenty healthy adolescents completed a baseline assessment (7 nights typical sleep) followed by assignment to SE or TS (5 nights). Participants returned to the lab to complete a frustrating computer game and two social interactions with a confederate peer (one naturalistic, one manipulated) during which adolescents were asked to up-regulate positive emotion. Following a frustrating task, the SE group reported increased positive emotions during the goal-directed interaction relative to both the naturalistic interaction and the TS group. Findings suggest another 30 minutes of sleep for five nights assisted adolescents in up-regulating positive emotional to meet socially relevant goals. Findings from this pilot study support the protective role of adequate sleep for social functioning and emotional health during adolescence.

High school students need support learning to evaluate online information. Scholarship in the last several years has explored how to provide this support via lessons that explicitly teach evaluation strategies. In this study, we analyzed classroom conversations in two high school government classrooms during lessons that taught "lateral reading", the strategy of leaving a website or post to investigate its source via external resources. Although lessons taught students to read laterally, they did not directly introduce factors that influence the credibility of a source, especially its expertise and trustworthiness. In the absence of such an introduction, we found that students frequently based their evaluations on a single facet of trustworthiness: a source's perspective. Further, students commonly determined a source's credibility not based on its expertise and trustworthiness but instead through factors like a website's contents, URL, or popularity. This study suggests that students need more support understanding what makes an online source credible and more practice examining the full range of elements that contribute to a source's credibility, from credentials and experience to conflicts of interest. Further, teachers need support that helps them plan for and provide this kind of practice.

Abstract Sleep disorders are common, and largely undiagnosed in early-career workers. The combination of sleep disorders and shift work has implications for mental health, workplace safety, and productivity. Early identification and management of sleep disorders is likely to be beneficial to workers, employers and the community more broadly. We assessed the feasibility and acceptability of a tailored sleep disorder screening and management pathway for individuals with future shift work requirements. Paramedic students were invited to complete an online sleep health survey, which included validated sleep disorder screening questionnaires for insomnia, obstructive sleep apnea and restless legs syndrome. Participants were able to express interest in participating in a sleep monitoring and management study. Participants at risk for a sleep disorder were identified, contacted by the study physician (RJA), notified of their sleep disorder screening results and provided with information regarding management options. Feasibility of the screening and management pathways were determined by completion of the 12 week follow-up, and ability to engage with health services for diagnostic testing or treatment. Acceptability of these pathways was assessed with a semi-structured interview on completion of the study at 12 weeks. Screening was completed in thirty participants (mean age 22.5 ± 6.7, 63% female), 17 of whom were ‘at-risk’ for a sleep disorder and offered a management pathway. All participants engaged with the study physician (RJA), with 16 completing the study (94% completion rate). Three participants with excessive daytime sleepiness received feedback from the study physician (RJA) and no further care required. Of the remaining 14 participants, 11 (78%) engaged with health services after speaking with the study physician (RJA). Those who engaged with diagnostic and management services reported that a structured pathway with online screening was convenient and easy to follow. Facilitating screening and management of sleep disorders in students with future shift work requirements is both feasible and acceptable. These findings can inform the development of a preventive strategy for sleep disorders and ideally, a health services feasibility trial for future shift workers.

We estimated hourly air–water gas transfer velocities (k600) for carbon dioxide in the Rhode River, a mesohaline sub-estuary of the Chesapeake Bay. Gas transfer velocities were calculated from estuary-specific parameterizations developed explicitly for shallow microtidal estuaries in the mid-Atlantic region of the United States, using standardized wind speed measurements. Combining the gas transfer velocity with continuous measurements of pCO2 in the water and in the overlying atmosphere, we determined the direction and magnitude of CO2 flux at hourly intervals across a 3-year record (1 July 2018 to 1 July 2021). Continuous year-round measurements enabled us to document strong seasonal cycling, whereby the Rhode River is primarily autotrophic during cold-water months (December–May) and largely net heterotrophic in warm-water months (June–November). Although there is inter-annual variability in CO2 flux in the Rhode River, the annual mean condition is near carbon neutral. Measurement at high temporal resolution across multiple years revealed that CO2 flux and apparent trophic status can reverse during a single 24 h period. pCO2 and CO2 flux are mediated by temperature effects on biological activity and are inverse to temperature-dependent physical solubility of CO2 in water. Biological/biogeochemical carbon fixation and mineralization are rapid and extensive, so sufficient sampling frequency is crucial to capture unbiased extremes and central tendencies of these estuarine ecosystems.

Abstract Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1113 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 48.2 min (95% limits of agreement (LoA): −50.3 to 146.8 min) for total sleep duration, −17.1 min for REM duration (95% LoA: −56.7 to 91.0 min) and 31.1 min (95% LoA: −67.3 to 129.5 min) for NREM duration. The sleep classifier was deployed in the UK Biobank with ~100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,262 UK Biobank participants, 1644 mortality events were observed. Short sleepers (

Objective Many unscheduled return visits to the emergency department (ED) stem from insufficient access to outpatient follow‐up. We piloted an emergency medicine‐staffed, on‐demand, virtual after care clinic (VACC) as an alternative for discharged ED patients. Methods Prospective cohort study of discharged ED patients who scheduled VACC appointments within 72 hours of index ED visit. We performed descriptive analyses and compared risks of ED return at 72 hours and 30 days between patients who did/did not attend their appointment. Results From March to December 2022, 309 patients scheduled VACC appointments and 210 (68%) attended them. Patients who scheduled appointments were young (median 37 years), non‐Hispanic white (80%), females (75%) with a primary care physicians (PCP) (90%), and commercial insurance (72%). Most VACC visits reinforced ED testing and/or treatment (64%) or adjusted medications (26%). VACC attendees were less likely to return to the ED within 72 h (3.3% vs. 13.1%; risk difference 9.3% [95% confidence interval, CI 2.7%‒19.8%]) and 30 days (16.2% vs. 30.3%; risk difference 14.1% [95% CI 3.8%‒24.4%]) compared to those who scheduled but did not attend a VACC appointment. VACC attendance was associated with lower odds of 72‐h (adjusted odds ratio [aOR] 0.0; 95% CI 0.0‒0.4) and 30‐day (aOR 0.4; 95% CI 0.2‒0.7) return ED visits. Conclusions In this pilot study, younger, white, female, commercially insured patients with a PCP preferentially scheduled VACC appointments. Among patients who scheduled VACC appointments, those who attended their appointments were less likely to return to the ED within 72 hours and 30 days than those who did not.

Maatskaplike werkers moet kan demonstreer dat die maatskaplikewerk- hulpverleningsintervensieswat hulle toepas, waarneembare uitkomste lewer in die lewens en omstandighedevan individue, groepe, gemeenskappe en organisasies. Laasgenoemde geld ook vir dieprogramme en projekte wat deur ’n welsynsorganisasie aangebied word. Hierdie verantwoordelikheidval saam met die staat se Kwaliteitsbeheerbeleid. Hierdie verantwoordelikheid is reedssedert die sewentigerjare van die vorige eeu sterk beklemtoon (Fanshel, 1980:32-35).Maatskaplike werkers het die verantwoordelikheid om aan kliënte, werkgewers, borge,subsidiërende liggame en die gemeenskap te kan toon dat hulle professionele dienslewering ’nbydrae tot die welsyn van die breër gemeenskap lewer. Hierdie verwagtinge ten opsigte vanmaatskaplike werkers is ook deur skrywers soos onder andere Bloom en Fischer (1982:476) enRoyse (1991:5) uitgewys. Loewenberg en Dolgoff (1992:223) sê in die verband: “Socialworkers are accountable to the people they serve, to their profession and to society.” Reeds in1993 noem Nelson (1994:65) die volgende in die verband: “In the past few years, socialworkers have been invited,…to evaluate their practice outcomes more objectively for greateraccountability to clients and agencies.” In die lig van die globaliseringsproses, die hoër eisewat die mens aan sy omgewing en diensleweringstrukture stel, die strewe na meer bruikbarekennis, asook die hoër opleidingstandaarde wat aan maatskaplike werkers gestel word om altydeties op te tree, word daar by die aanvang van die nuwe millennium verwag dat maatskaplikewerkers op ’n etiese en vaardige wyse praktyk-evaluering kan onderneem.Ten spyte daarvandat evaluering ’n integrale deel van die maatskaplike werker se professionele vaardighede vorm(Bloom & Fischer, 1982:476), bevraagteken skrywers soos Fischer (1993:19) en Nelson(1994:140) die wetenskaplikheid van die wyses waarop maatskaplike werkers hulledienslewering evalueer. Maatskaplike werkers evalueer dikwels die effektiwiteit van hulledienslewering aan die hand van die positiewe of negatiewe menings wat die kliënt(e) metbetrekking tot die bereiking van die beplande hulpverleningsdoelwitte uitspreek (Nelson,1994:141), of hulle steun op hulle eie subjektiewe waarneming of vooroordele (Grinnell,1997:9).

Abstract The rail industry in Australia screens workers for probable obstructive sleep apnea (OSA) due to known safety risks. However, existing criteria to trigger screening only identify a small proportion of workers with OSA. The current study sought to examine the relationship between OSA risk and rail incidents in real-world data from Australian train drivers, and conducted a proof of concept analysis to determine whether more conservative screening criteria are justified. Health assessment (2016–2018) and subsequent rail incident data (2016–2020) were collected from two passenger rail service providers. Predictors included OSA status (confirmed no OSA with a sleep study, controlled OSA, unknown OSA [no recorded sleep assessment data] and confirmed OSA with no indication of treatment); OSA risk according to the current Standard, and OSA risk according to more conservative clinical markers (BMI threshold and cardiometabolic burden). Coded rail safety incidents involving the train driver were included. Data were analysed using zero-inflated negative binomial models to account for over-dispersion with high 0 counts, and rail safety incidents are reported using Incidence Risk Ratios (IRRs). A total of 751 train drivers, typically middle-aged, overweight to obese and mostly men, were included in analyses. There were 43 (5.7%) drivers with confirmed OSA, 62 (8.2%) with controlled OSA, 13 (1.7%) with confirmed no OSA and 633 (84.4%) drivers with unknown OSA. Of the 633 train drivers with unknown OSA status, 21 (3.3%) met ‘at risk’ criteria for OSA according to the Standard, and incidents were 61% greater (IRR: 1.61, 95% Confidence Interval (CI) 1.02–2.56) in the years following their health assessment compared to drivers who did not meet ‘at risk’ criteria. A more conservative OSA risk status using lower BMI threshold and cardiometabolic burden identified an additional 30 ‘at risk’ train drivers who had 46% greater incidents compared to drivers who did not meet risk criteria (IRR (95% CI) 1.46 (1.00–2.13)). Our more conservative OSA risk criteria identified more workers, with greater prospective incidents. These findings suggest that existing validated tools could be considered in future iterations of the Standard in order to more sensitively screen for OSA.

Background: Airway management is a core component of the treatment of cardiac arrest. Where a rescuer cannot establish a patent airway to provide oxygenation and ventilation using standard basic and advanced airway techniques, there may be a need to consider emergency front-of-neck airway access (eFONA, e.g., cricothyroidotomy), but there is limited evidence to inform this approach. Objectives: This scoping review aims to identify the evidence for the use of eFONA techniques in patients with cardiac arrest. Methods: In November 2023, we searched Medline, Embase, and Cochrane Central to identify studies on eFONA in adults. We included randomised controlled trials, non-randomised studies, and case series with at least five cases that described any use of eFONA. We extracted data, including study setting, population characteristics, intervention characteristics, and outcomes. Our analysis focused on four key areas: incidence of eFONA, eFONA success rates, clinical outcomes, and complications. Results: The search identified 21,565 papers, of which 18,934 remained after de-duplication. After screening, we included 69 studies (53 reported incidence, 40 reported success rate, 38 reported clinical outcomes; 36 studies reported complications). We identified only one randomised controlled trial. Across studies, there was a total of 4,457 eFONA attempts, with a median of 31 attempts (interquartile range 16–56.5) per study. There was marked heterogeneity across studies that precluded any pooling of data. There were no studies that included only patients in cardiac arrest. Conclusion: The available evidence for eFONA is extremely heterogeneous, with no studies specifically focusing on its use in adults with cardiac arrest.

Understanding exercise metabolism and the relationship with volatile organic compounds (VOCs) holds potential in both health care and sports performance. Exercise metabolism can be investigated using whole body exercise testing (in vivo) or through the culture and subsequent electrical pulse stimulation (EPS) of myotubes (in vitro). This research investigates the novel headspace (HS) analysis of EPS skeletal muscle myotubes. An in vitro system was built to investigate the effect of EPS on the volatile constituents in the HS above EPS skeletal muscle. The C2C12 immortalised cell line was chosen. EPS was applied to the system to induce myotube contraction. The in vitro system was applied to the analysis of VOCs using thermal desorption (TD) sampling. Samples were collected under four conditions: environmental samples (enviro), acellular media HS samples (blank), skeletal muscle myotubes without stimulation HS samples (baseline) and EPS of skeletal muscle myotube HS samples (stim). TD sampling combined with gas-chromatography mass spectrometry (GC-MS) detected two compounds that, after multivariate and univariate statistical analysis, were identified as changing due to EPS (p < 0.05). These compounds were tentatively assigned as 1,4-Dioxane-2,5-dione, 3,6-dimethyl- and 1-pentene. The former is a known lactide and the latter has been reported as a marker of oxidative stress. Further research should focus on improvements to the EPS system, including the use of more relevant cell lines, quantification of myotube contractions, and the application of targeted analysis, metabolic assays and media analysis.

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations.

Abstract Prevotella intermedia, a Gram‐negative bacterium from the Bacteroidota phylum, is associated with periodontitis. Other species within this phylum are known to possess the general O‐glycosylation system. The O‐glycoproteome has been characterized in several species, including Tannerella forsythia, Porphyromonas gingivalis, and Flavobacterium johnsoniae. In our study, we used electron cryotomography (cryoET) and glycoproteomics to reveal the ultrastructure of P. intermedia and characterize its O‐glycoproteome. Our cryoET analysis unveiled the ultrastructural details of the cell envelope and outer membrane vesicles (OMVs) of P. intermedia. We observed an electron‐dense surface layer surrounding both cells and OMVs. The OMVs were often large (>200 nm) and presented two types, with lumens being either electron‐dense or translucent. LC‐MS/MS analyses of P. intermedia fractions led to the identification of 1655 proteins, which included 62 predicted T9SS cargo proteins. Within the glycoproteome, we identified 443 unique O‐glycosylation sites within 224 glycoproteins. Interestingly, the O‐glycosylation motif exhibited a broader range than reported in other species, with O‐glycosylation found at D(S/T)(A/I/L/M/T/V/S/C/G/F/N/E/Q/D/P). We identified a single O‐glycan with a delta mass of 1531.48 Da. Its sequence was determined by MS2 and MS3 analyses using both collision‐induced dissociation and high‐energy collisional dissociation fragmentation modes. After partial deglycosylation with trifluoromethanesulfonic acid, the O‐glycan sequence was confirmed to be dHex‐dHex‐HexNAc (HPO3‐C6H12O5)‐dHex‐Hex‐HexA‐Hex(dHex). Bioinformatic analyses predicted the localization of O‐glycoproteins, with 73 periplasmic proteins, 53 inner membrane proteins, 52 lipoproteins, 26 outer membrane proteins, and 14 proteins secreted by the T9SS.

Abstract Objectives Sex‐specific disparities in morbidity and mortality of COVID‐19 illness are not well understood. Neutralizing antibodies (Ab) may protect against severe COVID‐19 illness. We investigated the association of sex with disease progression and SARS‐CoV‐2 Ab response. Methods In this exploratory analysis of the phase 3, multicenter, randomized, placebo‐controlled Convalescent Plasma in Outpatients (C3PO) trial, we examined whether sex was associated with progression to severe illness, defined as a composite of all‐cause hospitalization, emergency/urgent care visit, or death within 15 days from study enrollment. Patients had a positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) test, symptom onset within 7 days, stable condition for emergency department discharge, and were either ≥50 years old or had at least one high‐risk feature for disease progression. Patients received blinded convalescent plasma or placebo in a 1:1 fashion and were evaluated on days 15 and 30 after infusion. Blood samples were collected on day 0 (pre‐/post‐infusion), 15, and 30 to measure Ab levels with the Broad Institute using the Plaque Reduction Neutralization Test assay. Results Of 511 patients enrolled (median age 54 [Iinterquartile range 41–62] years, 46% male, 66% white, 20% black, 3.5% Asian), disease progression occurred in 36.7% of males and 25.9% of females (unadjusted risk difference 10.8%, 95% confidence interval [CI], 2.8–18.8%). Sex‐disparities did not persist when adjusted for treatment group, age, viremic status, symptom onset, and tobacco use (adjusted risk difference 5.6%, 95% confidence interval [CI], −2.2% to 13.4%), but were present in the subgroup presenting 3 or more days after symptom onset (adjusted risk difference 12.6%, 95% CI, 3.4% to 21.9%). Mean baseline Ab levels (log scale) available for 367 patients were similar between sexes (difference 0.19 log units, 95% CI, −0.08 to 0.46). The log‐scale mean increase from baseline to day 15 after adjusting for treatment assignment and baseline levels was larger in males than females (3.26 vs. 2.67). A similar difference was noted when the groups were subdivided by outcome. Conclusions Progression of COVID‐19 was similar in males and females when adjusted for age, tobacco use, and viremia status in this study. However, in the cohort presenting 3 or more days after symptom onset, COVID‐19 outcomes were worse in males than females. Neutralizing Ab levels increased more in males but did not correlate with sex differences in outcomes.

Abstract Objective: To compare the agreement and cost of two recall methods for estimating children’s minimum dietary diversity (MDD). Design: We assessed child’s dietary intake on two consecutive days: an observation on day one, followed by two recall methods (list-based recall and multiple-pass recall) administered in random order by different enumerators at two different times on day two. We compared the estimated MDD prevalence using survey-weighted linear probability models following a two one-sided test equivalence testing approach. We also estimated the cost-effectiveness of the two methods. Setting: Cambodia (Kampong Thom, Siem Reap, Battambang, and Pursat provinces) and Zambia (Chipata, Katete, Lundazi, Nyimba, and Petauke districts). Participants: Children aged 6–23 months: 636 in Cambodia and 608 in Zambia. Results: MDD estimations from both recall methods were equivalent to the observation in Cambodia but not in Zambia. Both methods were equivalent to the observation in capturing most food groups. Both methods were highly sensitive although the multiple-pass method accurately classified a higher proportion of children meeting MDD than the list-based method in both countries. Both methods were highly specific in Cambodia but moderately so in Zambia. Cost-effectiveness was better for the list-based recall method in both countries. Conclusion: The two recall methods estimated MDD and most other infant and young child feeding indicators equivalently in Cambodia but not in Zambia, compared to the observation. The list-based method produced slightly more accurate estimates of MDD at the population level, took less time to administer and was less costly to implement.

Abstract Mental health conditions confer considerable global disease burden in young adults, who are also the highest demographic to work shifts, and of whom 20% meet criteria for a sleep disorder. We aimed to establish the relationship between the combined effect of shift work and sleep disorders, and mental health. The Raine Study is the only longitudinal, population-based birth cohort in the world with gold-standard, Level 1 measurement of sleep (polysomnography, PSG) collected in early adulthood. Participants (aged 22y) underwent in-laboratory PSG and completed detailed sleep questionnaires. Multivariable adjusted robust linear regression models were conducted to explore associations with anxiety (GAD7) and depression (PHQ9), adjusted for sex, health comorbidities, and work hours/week. Data were from 660 employed young adults (27.3% shift workers). At least one clinically significant sleep disorder was present in 18% of shift workers (day, evening and night shifts) and 21% of non-shift workers (p = 0.51); 80% were undiagnosed. Scores for anxiety and depression were not different between shift and non-shift workers (p = 0.29 and p = 0.82); but were higher in those with a sleep disorder than those without (Md(IQR) anxiety: 7.0(4.0–10.0) vs 4.0(1.0–6.0)), and depression: (9.0(5.0–13.0) vs 4.0(2.0–6.0)). Considering evening and night shift workers only (i.e. excluding day shift workers) revealed an interaction between shift work and sleep disorder status for anxiety (p = 0.021), but not depression (p = 0.96), with anxiety scores being highest in those shift workers with a sleep disorder (Md(IQR) 8.5(4.0–12.2). We have shown that clinical sleep disorders are common in young workers and are largely undiagnosed. Measures of mental health do not appear be different between shift and non-shift workers. These findings indicate that the identification and treatment of clinical sleep disorders should be prioritised for young workers as these sleep disorders, rather than shift work per se, are associated with poorer mental health. These negative mental health effects appear to be greatest in those who work evening and/or night shift and have a sleep disorder.

Abstract Assessment of enamel subsurface lesion remineralisation is essential for the evaluation of novel remineralisation technologies. The gold standard to assess subsurface mineral gain of enamel lesions is transverse microradiography (TMR). However, some studies have utilised surface microhardness (SMH) to evaluate efficacy of remineralisation agents. The aim of this study was to assess remineralisation of enamel subsurface lesions using TMR and SMH after in vitro treatment with calcium-containing technologies, and to test correlation between the TMR and SMH measurements. The parameters obtained from the TMR and SMH analyses of enamel subsurface remineralisation were not significantly correlated. Furthermore, the enamel subsurface remineralisation as measured by TMR was significantly correlated with the water-soluble calcium concentration of the remineralisation products. Scanning electron microscopy revealed surface precipitates formed by specific remineralisation treatments obfuscated accurate assessment of remineralisation by SMH. It was concluded that TMR is a more appropriate method for analysis of enamel subsurface remineralisation, and that SMH values of remineralised enamel should be interpreted with caution. Using TMR the level of remineralisation (%R) by the different technologies was CPP-ACP/F (31.3 ± 1.4%); CPP-ACP (24.2 ± 1.4%); CaSO4/K2HPO4/F (21.3 ± 1.4%); f-TCP/F (20.9 ± 1.0%); Nano-HA/F (16.3 ± 0.3%); Nano-HA (15.3 ± 0.6%) and F alone control (15.4 ± 1.3%).

Introduction Mechanical ventilator breaths provided to deeply sedated patients have an abnormal volume distribution, encouraging alveolar collapse in dependent regions and promoting alveolar overdistention in non-dependent regions. Collapse and overdistention both start with the first breath and worsen over time, driving ventilator-induced lung injury (VILI). This is exacerbated when the lung is already injured or has increased heterogeneity. Our study investigated the impact of a single episode of lung injury on lung mechanics and the risk factors for ventilator-induced injury, compared with non-injured lungs. Methods Two groups of pigs were sedated and ventilated using lung-protective volume-controlled mode at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmH~2~O, with respiratory rate and FiO2 set to maintain normal blood gas values. Animals in one group were ventilated for 50 h (50-Hour MV group, n=10). Animals in the second group had lung injury induced using oleic acid and were ventilated for 12 h post-injury (LI MV group, n=6). Both groups were compared with a never-ventilated control group (NV, n=6). Lung mechanics and injury were measured using electrical impedance tomography, esophageal pressure monitoring and tissue histology. Results End-expiratory lung-volume loss was greater in the 50-Hour MV group (P\

Abstract Mechanical ventilation is the cornerstone of the Intensive Care Unit. However, it has been associated with many negative consequences. Recently, ventilator-induced brain injury has been reported in rodents under injurious ventilation settings. Our group wanted to explore the extent of brain injury after 50 h of mechanical ventilation, sedation and physical immobility, quantifying hippocampal apoptosis and inflammation, in a normal-lung porcine study. After 50 h of lung-protective mechanical ventilation, sedation and immobility, greater levels of hippocampal apoptosis and neuroinflammation were clearly observed in the mechanically ventilated group, in comparison to a never-ventilated group. Markers in the serum for astrocyte damage and neuronal damage were also higher in the mechanically ventilated group. Therefore, our study demonstrated that considerable hippocampal insult can be observed after 50 h of lung-protective mechanical ventilation, sedation and physical immobility.

Abstract Calcium added to dentifrices can complex with fluoride ions to reduce intra-oral bioavailability and therefore efficacy in preventing dental caries. Six commercially available dentifrices containing different types of calcium and fluoride were analyzed for total and bioavailable fluoride levels by adding 10 g of dentifrice to 30 mL of distilled deionized water and mixing vigorously for 1 min to simulate toothbrushing. One milliliter of the dentifrice/water slurry was immediately centrifuged and the supernatant removed for bioavailable fluoride analysis and the mixed slurry prior to centrifugation used for total fluoride analysis using a modified microdiffusion method. The concentration of fluoride was determined using a fluoride ion-selective electrode calibrated with internal fluoride standards. All the dentifrices had similar total fluoride concentrations to those indicated on their labels (94% to 105%). However, only one dentifrice that contained calcium in the form of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) had almost 100% (97%) of fluoride in bioavailable form. The other dentifrices contained calcium carbonate and they exhibited significantly (p

Exercise has beneficial effects on metabolism and overall physiologic fitness in aged organisms. Here the authors show that MOTS-c is a mitochondrial-encoded exercise-induced peptide that regulates skeletal muscle metabolism and improves healthspan of older mice.

Shift work is associated with adverse chronic health outcomes. Addressing chronic disease risk factors including biomedical risk factors, behavioural risk factors, as well as sleep and perceived health status, affords an opportunity to improve health outcomes in shift workers. The present study aimed to conduct a systematic review, qualitative synthesis, and meta-analysis of non-pharmacological interventions targeting chronic disease risk factors, including sleep, in shift workers. A total of 8465 records were retrieved; 65 publications were eligible for inclusion in qualitative analysis. Random-effects meta-analysis were conducted for eight eligible health outcomes, including a total of thirty-nine studies. Interventions resulted in increased objective sleep duration (Hedges’ g = 0.73; CI: 0.36, 1.10, k = 16), improved objective sleep efficiency (Hedges’ g = 0.48; CI: 0.20, 0.76, k = 10) and a small increase in both subjective sleep duration (Hedges’ g = 0.11; CI: −0.04, 0.27, k = 19) and sleep quality (Hedges’ g = 0.11; CI: −0.11, 0.33, k = 21). Interventions also improved perceived health status (Hedges’ g = 0.20; CI: −0.05, 0.46, k = 8), decreased systolic (Hedges’ g = 0.26; CI: −0.54, 0.02, k = 7) and diastolic (Hedges’ g = 0.06; CI: −0.23, 0.36, k = 7) blood pressure, and reduced body mass index (Hedges’ g = −0.04; CI: −0.37, 0.29, k = 9). The current study suggests interventions may improve chronic disease risk factors and sleep in shift workers; however, this could only be objectively assessed for a limited number of risk factor endpoints. Future interventions could explore the impact of non-pharmacological interventions on a broader range of chronic disease risk factors to better characterise targets for improved health outcomes in shift workers.

On-call work arrangements are commonly utilised in the emergency services sector and are consistency associated with inadequate sleep. Despite sleep being a common shared behaviour, studies are yet to assess the impact of on-call work on the sleep of co-sleeping partners. This study aimed to investigate whether frequent 24/7 on-call work impacted the sleep and relationship happiness of firefighters’ partners. Two key research questions were investigated: (1) Does the frequency of calls impact sleep and relationship happiness? and, (2) Does the (a) sleep quantity and (b) sleep quality of partners impact perceived relationship happiness? A cross-sectional study was conducted using an online questionnaire completed by partners of on-call workers (n = 66; 93% female). The questionnaire included items on (i) sleep quantity and quality, (ii) on-call sleep disturbances and, (iii) relationship happiness. Responses were analysed using logistic regression models. Higher overnight call frequency was associated with greater self-reported levels of inadequate sleep (p = 0.024). Support for continuance of a firefighter’s role was less likely if the partner reported they regularly had trouble falling asleep within 30 min (p < 0.001). There were no other significant relationships between the frequency of calls or other sleep quantity or quality variables and relationship happiness. This study provides important first insights into how firefighters’ on-call work arrangements impact partners’ sleep. Future research is needed across periods of high and low call demand, using objective measures of sleep to further define the impacts of on-call work on partners’ sleep.

ABSTRACT The type IX secretion system (T9SS) transports cargo proteins through the outer membrane of Bacteroidetes and attaches them to the cell surface for functions including pathogenesis, gliding motility, and degradation of carbon sources. The T9SS comprises at least 20 different proteins and includes several modules: the trans-envelope core module comprising the PorL/M motor and the PorK/N ring, the outer membrane Sov translocon, and the cell attachment complex. However, the spatial organization of these modules is unknown. We have characterized the protein interactome of the Sov translocon in Porphyromonas gingivalis and identified Sov-PorV-PorA as well as Sov-PorW-PorN-PorK to be novel networks. PorW also interacted with PGN_1783 (PorD), which was required for maximum secretion efficiency. The identification of PorW as the missing link completes a continuous interaction network from the PorL/M motor to the Sov translocon, providing a pathway for cargo delivery and energy transduction from the inner membrane to the secretion pore. IMPORTANCE The T9SS is a newly identified protein secretion system of the Fibrobacteres-Chlorobi-Bacteroidetes superphylum used by pathogens associated with diseases of humans, fish, and poultry for the secretion and cell surface attachment of virulence factors. The T9SS comprises three known modules: (i) the trans-envelope core module comprising the PorL/M motor and the PorK/N ring, (ii) the outer membrane Sov translocon, and (iii) the cell surface attachment complex. The spatial organization and interaction of these modules have been a mystery. Here, we describe the protein interactome of the Sov translocon in the human pathogen Porphyromonas gingivalis and have identified PorW as the missing link which bridges PorN with Sov and so completes a continuous interaction network from the PorL/M motor to the Sov translocon, providing, for the first time, a pathway for cargo delivery and energy transduction from the inner membrane to the secretion pore.

ABSTRACT Porphyromonas gingivalis is an important human pathogen and also a model organism for the Bacteroidetes phylum. O-glycosylation has been reported in this phylum with findings that include the O-glycosylation motif, the structure of the O-glycans in a few species, and an extensive O-glycoproteome analysis in Tannerella forsythia. However, O-glycosylation has not yet been confirmed in P. gingivalis. We therefore used glycoproteomics approaches including partial deglycosylation with trifluoromethanesulfonic acid as well as both HILIC and FAIMS based glycopeptide enrichment strategies leading to the identification of 257 putative glycosylation sites in 145 glycoproteins. The sequence of the major O-glycan was elucidated to be HexNAc-HexNAc(P-Gro-[Ac]0-2)-dHex-Hex-HexA-Hex(dHex). Western blot analyses of mutants lacking the glycosyltransferases PGN_1134 and PGN_1135 demonstrated their involvement in the biosynthesis of the glycan while mass spectrometry analysis of the truncated O-glycans suggested that PGN_1134 and PGN_1135 transfer the two HexNAc sugars. Interestingly, a strong bias against the O-glycosylation of abundant proteins exposed to the cell surface such as abundant T9SS cargo proteins, surface lipoproteins, and outer membrane β-barrel proteins was observed. In contrast, the great majority of proteins associated with the inner membrane or periplasm were glycosylated irrespective of their abundance. The P. gingivalis O-glycosylation system may therefore function to establish the desired physicochemical properties of the periplasm. IMPORTANCE Porphyromonas gingivalis is an oral pathogen primarily associated with severe periodontal disease and further associated with rheumatoid arthritis, dementia, cardiovascular disease, and certain cancers. Protein glycosylation can be important for a variety of reasons including protein function, solubility, protease resistance, and thermodynamic stability. This study has for the first time demonstrated the presence of O-linked glycosylation in this organism by determining the basic structure of the O-glycans and identifying 257 glycosylation sites in 145 proteins. It was found that most proteins exposed to the periplasm were O-glycosylated; however, the abundant surface exposed proteins were not. The O-glycans consisted of seven monosaccharides and a glycerol phosphate with 0–2 acetyl groups. These glycans are likely to have a stabilizing role to the proteins that bear them and must be taken into account when the proteins are produced in heterologous organisms.

Abstract Background Most guidelines recommend both pelvic packing (PP) and angioembolization for hemodynamically unstable pelvic fractures, however their sequence varies. Some argue to use PP first because orthopaedic surgeons are more available than interventional radiologists; however, there is no data confirming this. Methods This cross-sectional survey of 158 trauma medical directors at US Level I trauma centers collected the availability of orthopaedic surgeons and interventional radiologists, the number of orthopaedic trauma surgeons trained to manage pelvic fractures, and priority treatment sequence for hemodynamically unstable pelvic fractures. The study objective was to compare the availability of orthopaedic surgeons to interventional radiologists and describe how the availability of orthopaedic surgeons and interventional radiologists affects the treatment sequence for hemodynamically unstable pelvic fractures. Fisher’s exact, chi-squared, and Kruskal-Wallis tests were used, alpha = 0.05. Results The response rate was 25% (40/158). Orthopaedic surgeons (86%) were on-site more often than interventional radiologists (54%), p = 0.003. Orthopaedic surgeons were faster to arrive 39% of the time, and interventional radiologists were faster to arrive 6% of the time. There was a higher proportion of participants who prioritized PP before angioembolization at centers with above the average number (> 3) of orthopaedic trauma surgeons trained to manage pelvic fractures, as among centers with equal to or below average, p = 0.02. Arrival times for orthopaedic surgeons did not significantly predict prioritization of angioembolization or PP. Conclusions Our results provide evidence that orthopaedic surgeons typically are more available than interventional radiologists but contrary to anecdotal evidence most participants used angioembolization first. Familiarity with the availability of orthopaedic surgeons and interventional radiologists may contribute to individual trauma center’s treatment sequence.

Abstract Background Fatty acids, specifically polyunsaturated fatty acids (PUFAs) play an important role in inflammation and its resolution, however, their interaction with the epigenome is relatively unexplored. Here we investigate the relationship between circulating blood fatty acids and the DNA methylation of the cytokine encoding gene tumour necrosis factor (TNF, OMIM 191160). Methods Using a cross‐sectional study approach, we collected blood samples from adults (N=88 (30 males, 58 females); 18–74 years old) for DNA methylation pyrosequencing analysis at four sites in TNF exon 1 and gas‐chromatography mass‐spectrometry analysis of the fatty acid profile of dried blood spots (DBS). Results Methylation levels of TNF exon 1 are significantly correlated with specific fatty acids in a gender‐specific manner. In the males the PUFAs Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) were positively associated with TNF methylation, as was the saturated fatty acid (SFA) Stearic Acid; in contrast, mono‐unsaturated fatty acids (MUFAs) had a negative association. In the females, omega‐6 PUFA γ‐Linolenic acid (GLA) was negatively correlated with TNF methylation; Adrenic acid and Eicosadienoic Acid were positively correlated with TNF methylation. Conclusion These results suggest that one way that fatty acids interact with the inflammation is through altered methylation profiles of cytokine genes; thus, providing potential therapeutic targets for nutritional and health interventions.

Tannerella forsythia

Abstract Background In Iowa from 2014 to 2017, there were 2 separate public dental benefit programs for Medicaid-enrolled adults: one for the Medicaid expansion population called the Dental Wellness Plan (DWP), and one for the traditional, non-expansion adult Medicaid population. The programs differed with respect to reimbursement, administration, and benefit structure. This study explored differences in patterns and predictors of dentist participation in the two programs. Methods Authors sent a survey to all private practice dentists in Iowa (n = 1301) 2 years after DWP implementation. Descriptive, bivariate, and logistic regression analyses were used to examine patterns and predictors of dentist participation in Medicaid and DWP. Results Overall rates of dentists’ acceptance of new Medicaid and DWP patients were 45 and 43%, respectively. However, Medicaid participants were much more likely than DWP participants to place limits on patient acceptance. Adjusting for other factors, practice busyness was the only significant predictor of DWP participation, and practice location was the only significant predictor of Medicaid participation. Dentists who were not busy enough were more than twice as likely to participate in DWP compared to others, and dentists in rural areas were almost twice as likely to participate in Medicaid compared to dentists in urban areas. Conclusions Dentist participation in Medicaid is an ongoing concern for states aiming to ensure access to dental care for low-income populations. We found distinct participation patterns and predictors between a traditional Medicaid dental program and the DWP, suggesting different motivations for participation between the two programs.

Summary Objectives Lipodystrophies are characterized by regional or generalized loss of adipose tissue and severe metabolic complications. The role of visceral adipose tissue (VAT) in the development of metabolic derangements in lipodystrophy is unknown. The study aim was to investigate VAT contribution to metabolic disease in lipodystrophy versus healthy controls. Methods Analysis of correlations between VAT volume and biomarkers of metabolic disease in 93 patients and 93 age/sex‐matched healthy controls. Results Patients with generalized lipodystrophy (n = 43) had lower VAT compared with matched controls, while those with partial lipodystrophy (n = 50) had higher VAT versus controls. Both groups with lipodystrophy had lower leg fat mass versus controls (p 0.05 for all; Spearman correlation). In controls matched to patients with generalized or partial lipodystrophy, VAT correlated with glucose (R = 0.42 and 0.36), triglycerides (R = 0.36 and 0.60) and high‐density lipoprotein cholesterol (R = −0.34 and −0.64) (p

Objectives There is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should be built using the concepts of human-centred design, fit within clinical workflows and provide solutions to priority problems.Methods We adapted a commercially available diagnostic decision support system (DDSS) to use extracted findings from a patient record and combine them with genomic variant information in the DDSS interface. Three representative patient cases were created in a simulated clinical environment for user testing. A semistructured interview guide was created to illuminate factors relevant to human factors in CDS design and organisational implementation.Results Six individuals completed the user testing process. Tester responses were positive and noted good fit with real-world clinical genetics workflow. Technical issues related to interface, interaction and design were minor and fixable. Testers suggested solving issues related to terminology and usability through training and infobuttons. Time savings was estimated at 30%–50% and additional uses such as in-house clinical variant analysis were suggested for increase fit with workflow and to further address priority problems.Conclusion This study provides preliminary evidence for usability, workflow fit, acceptability and implementation potential of a modified DDSS that includes machine-assisted chart review. Continued development and testing using principles from human-centred design and implementation science are necessary to improve technical functionality and acceptability for multiple stakeholders and organisational implementation potential to improve the genomic diagnosis process.

Background On-call research and guidance materials typically focus on ‘traditional’ on-call work (e.g., emergency services, healthcare). However, given the increasing prevalence of non-standard employment arrangements (e.g., gig work and casualisation), it is likely that a proportion of individuals who describe themselves as being on-call are not included in current on-call literature. This study therefore aimed to describe the current sociodemographic and work characteristics of Australian on-call workers. Methods A survey of 2044 adults assessed sociodemographic and work arrangements. Of this population, 1057 individuals were workforce participants, who were asked to provide information regarding any on-call work they performed over the last three months, occupation type, weekly work hours, and the presence or absence of non-standard work conditions. Results Of respondents who were working, 45.5% reported working at least one day on-call in the previous month. There was a high prevalence of on-call work in younger respondents (63.1% of participants aged 18–24 years), and those who worked multiple jobs and more weekly work hours. Additionally, high prevalence rates of on-call work were reported by machinery operators, drivers, community and personal service workers, sales workers, and high-level managers. Conclusions These data suggest that on-call work is more prevalent than previously recorded and is likely to refer to a broad set of employment arrangements. Current classification systems may therefore be inadequate for population-level research. A taxonomy for the classification of on-call work is proposed, incorporating traditional on-call work, gig economy work, relief, or unscheduled work, and out of hours work.

Footprints are left, or obtained, in a variety of scenarios from crime scenes to anthropological investigations. Determining the sex of a footprint can be useful in screening such impressions and attempts have been made to do so using single or multi landmark distances, shape analyses and via the density of friction ridges. Here we explore the relative importance of different components in sexing two-dimensional foot impressions namely, size, shape and texture. We use a machine learning approach and compare this to more traditional methods of discrimination. Two datasets are used, a pilot data set collected from students at Bournemouth University (N = 196) and a larger data set collected by podiatrists at Sheffield NHS Teaching Hospital (N = 2677). Our convolutional neural network can sex a footprint with accuracy of around 90% on a test set of N = 267 footprint images using all image components, which is better than an expert can achieve. However, the quality of the impressions impacts on this success rate, but the results are promising and in time it may be possible to create an automated screening algorithm in which practitioners of whatever sort (medical or forensic) can obtain a first order sexing of a two-dimensional footprint.

Background: The cell-surface cysteine proteinases RgpA, RgpB (Arg-gingipain), and Kgp (Lys-gingipain) are major virulence factors of P. gingivalis, a keystone pathogen in the development of destructive periodontal disease. The gingipains function as proteinases and transpeptidases utilising small peptides such as glycylglycine as acceptor molecules. However, the characteristics of the gingipains from most P. gingivalis strains have not been determined. Methods: We determined the phenotypes of a panel of P. gingivalis laboratory strains and global clinical isolates with respect to growth on blood agar plus whole-cell and vesicle-free culture supernatant (VFSN) Arg- and Lys-specific proteinase activities. Results: The P. gingivalis isolates exhibited different growth characteristics and hydrolysis of haemoglobin in solid media. Whole-cell Arg-gingipain Vmax varied 5.8-fold and the whole cell Lys-gingipain Vmax varied 2.1-fold across the strains. Furthermore, the P. gingivalis strains showed more than 107-fold variance in soluble Arg-gingipain activity in VFSN and more than 371-fold variance in soluble Lys-gingipain activity in VFSN. Glycylglycine and cysteine stimulated Arg- and Lys-specific cleavage activities of all strains. The stimulation by cysteine was in addition to its redox effect consistent with both glycylglycine and cysteine promoting transpeptidation. Conclusion: The global P. gingivalis clinical isolates exhibit different Arg- and Lys‑gingipain activities with substantial variability in the level of soluble proteinases released into the environment.

ABSTRACT Porphyromonas gingivalis and Tannerella forsythia use the type IX secretion system to secrete cargo proteins to the cell surface where they are anchored via glycolipids. In P. gingivalis, the glycolipid is anionic lipopolysaccharide (A-LPS), of partially known structure. Modified cargo proteins were deglycosylated using trifluoromethanesulfonic acid and digested with trypsin or proteinase K. The residual modifications were then extensively analyzed by tandem mass spectrometry. The C terminus of each cargo protein was amide-bonded to a linking sugar whose structure was deduced to be 2-N-seryl, 3-N-acetylglucuronamide in P. gingivalis and 2-N-glycyl, 3-N-acetylmannuronic acid in T. forsythia. The structures indicated the involvement of the Wbp pathway to produce 2,3-di-N-acetylglucuronic acid and a WbpS amidotransferase to produce the uronamide form of this sugar in P. gingivalis. The wbpS gene was identified as PGN_1234 as its deletion resulted in the inability to produce the uronamide. In addition, the P. gingivalis vimA mutant which lacks A-LPS was successfully complemented by the T. forsythia vimA gene; however, the linking sugar was altered to include glycine rather than serine. After removal of the acetyl group at C-2 by the putative deacetylase, VimE, VimA presumably transfers the amino acid to complete the biosynthesis. The data explain all the enzyme activities required for the biosynthesis of the linking sugar accounting for six A-LPS-specific genes. The linking sugar is therefore the key compound that enables the attachment of cargo proteins in P. gingivalis and T. forsythia. We propose to designate this novel linking sugar biosynthetic pathway the Wbp/Vim pathway. IMPORTANCE Porphyromonas gingivalis and Tannerella forsythia, two pathogens associated with severe gum disease, use the type IX secretion system (T9SS) to secrete and attach toxic arrays of virulence factor proteins to their cell surfaces. The proteins are tethered to the outer membrane via glycolipid anchors that have remained unidentified for more than 2 decades. In this study, the first sugar molecules (linking sugars) in these anchors are identified and found to be novel compounds. The novel biosynthetic pathway of these linking sugars is also elucidated. A diverse range of bacteria that do not have the T9SS were found to have the genes for this pathway, suggesting that they may synthesize similar linking sugars for utilization in different systems. Since the cell surface attachment of virulence factors is essential for virulence, these findings reveal new targets for the development of novel therapies.

Knowing the difference between left and right is generally assumed throughout the brain MRI research community. However, we note widespread occurrences of left-right orientation errors in MRI open database repositories where volumes have contained systematic left-right flips between subject EPIs and anatomicals, due to having incorrect or missing file header information. Here we present a simple method in AFNI for determining the consistency of left and right within a pair of acquired volumes for a particular subject; the presence of EPI-anatomical inconsistency, for example, is a sign that dataset header information likely requires correction. The method contains both a quantitative evaluation as well as a visualizable verification. We test the functionality using publicly available datasets. Left-right flipping is not immediately obvious in most cases, so we also present visualization methods for looking at this problem (and other potential problems), using examples from both FMRI and DTI datasets.