2023 Cardiac Society of Australia and New Zealand Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF.

Current status of the adjustable transobturator male system (ATOMSTM) for male stress urinary incontinence.

Male stress urinary incontinence is a debilitating condition, which can occur after prostate surgery. In persistent cases, surgery is indicated and a number of options are available. This includes one of the male slings, Adjustable transobturator male system (ATOMSTM, A.M.I, Austria). There are now an increasing number of studies published. This review provides an overview of the current status of this implant device including technical considerations, surgical outcomes and potential advantages and disadvantages compared to alternatives such as the artificial urinary sphincter.

Type 2 Diabetes, the Epidemic: Trends in Prevalence and Incidence, 2004-2020.

Aims/Hypothesis: Only a few studies reported the incidence of type 2 diabetes (T2D). Understanding recent trends in diabetes is vital for planning future diabetes care. This study updated national trends in the prevalence and incidence of type 2 diabetes (T2D) in the Netherlands from 2004-2020. Methods: The DIAbetes, MANagement and Treatment (DIAMANT) cohort was used. A cross-sectional design with yearly measurements for the study period was used. The prevalence was calculated by dividing the total number of people with T2D by the total number of all residents. The incidence was calculated by dividing new cases of T2D by the resident population at risk during the calendar year of interest. Results: Among men, the prevalence of T2D in the Netherlands increased from 2.3% in 2004 to 6.3% in 2020. Women's prevalence increased from 2.3% in 2004 to 5.3% in 2020. During 2005-2009, the incidence rate for both men and women was relatively stable Between 2010 and 2020, the incidence rate fell about 1.5 per 1000 in both men and women. Conclusion: From 2004-2020, the prevalence of T2D in the Netherlands more than doubled, with a decreasing incidence from 2010 onwards.

Research in context What is already known about this subject? Many studies have reported the increasing prevalence of type 2 diabetes (T2D). However, only a few studies reported the incidence.In a recent systematic review of all these studies, the incidence fell in over a third of the most high-income populations and increased in a minority of populations. Data from the Netherlands were included, but they date back to 1996.Understanding recent trends in diabetes, the prevalence and incidence are vital for planning future diabetes care.What is the key question? To update national trends in the prevalence and incidence of T2D in the Netherlands for 2004-2020.What are the new findings? During 2004-2020, the prevalence of T2D in the Netherlands more than doubled, with a decreasing incidence from 2010 onwards.How might this impact on clinical practice in the foreseeable future? It demonstrates the effectiveness of preventive strategies, public health education and awareness campaigns contributing to this trend.

Chaos and COSMOS-Considerations on QSM methods with multiple and single orientations and effects from local anisotropy.

PURPOSE: Field-to-susceptibility inversion in quantitative susceptibility mapping (QSM) is ill-posed and needs numerical stabilization through either regularization or oversampling by acquiring data at three or more object orientations. Calculation Of Susceptibility through Multiple Orientations Sampling (COSMOS) is an established oversampling approach and regarded as QSM gold standard. It achieves a well-conditioned inverse problem, requiring rotations by 0°, 60° and 120° in the yz-plane. However, this is impractical in vivo, where head rotations are typically restricted to a range of ±25°. Non-ideal sampling degrades the conditioning with residual streaking artifacts whose mitigation needs further regularization. Moreover, susceptibility anisotropy in white matter is not considered in the COSMOS model, which may introduce additional bias. The current work presents a thorough investigation of these effects in primate brain. METHODS: Gradient-recalled echo (GRE) data of an entire fixed chimpanzee brain were acquired at 7 T (350 µm resolution, 10 orientations) including ideal COSMOS sampling and realistic rotations in vivo. Comparisons of the results included ideal COSMOS, in-vivo feasible acquisitions with 3-8 orientations and single-orientation iLSQR QSM. RESULTS: In-vivo feasible and optimal COSMOS yielded high-quality susceptibility maps with increased SNR resulting from averaging multiple acquisitions. COSMOS reconstructions from non-ideal rotations about a single axis required additional L2-regularization to mitigate residual streaking artifacts. CONCLUSION: In view of unconsidered anisotropy effects, added complexity of the reconstruction, and the general challenge of multi-orientation acquisitions, advantages of sub-optimal COSMOS schemes over regularized single-orientation QSM appear limited in in-vivo settings.

Detecting rhythmic spiking through the power spectra of point process model residuals.

Objective: Oscillations figure prominently as neurological disease hallmarks and neuromodulation targets. To detect oscillations in a neuron's spiking, one might attempt to seek peaks in the spike train's power spectral density (PSD) which exceed a flat baseline. Yet for a non-oscillating neuron, the PSD is not flat: The recovery period ("RP", the post-spike drop in spike probability, starting with the refractory period) introduces global spectral distortion. An established "shuffling" procedure corrects for RP distortion by removing the spectral component explained by the inter-spike interval (ISI) distribution. However, this procedure sacrifices oscillation-related information present in the ISIs, and therefore in the PSD. We asked whether point process models (PPMs) might achieve more selective RP distortion removal, thereby enabling improved oscillation detection. Approach: In a novel "residuals" method, we first estimate the RP duration (nr) from the ISI distribution. We then fit the spike train with a PPM that predicts spike likelihood based on the time elapsed since the most recent of any spikes falling within the preceding nr milliseconds. Finally, we compute the PSD of the model's residuals. Main results: We compared the residuals and shuffling methods' ability to enable accurate oscillation detection with flat baseline-assuming tests. Over synthetic data, the residuals method generally outperformed the shuffling method in classification of true- versus false-positive oscillatory power, principally due to enhanced sensitivity in sparse spike trains. In single-unit data from the internal globus pallidus (GPi) and ventrolateral anterior thalamus (VLa) of a parkinsonian monkey -- in which alpha-beta oscillations (8-30 Hz) were anticipated -- the residuals method reported the greatest incidence of significant alpha-beta power, with low firing rates predicting residuals-selective oscillation detection. Significance: These results encourage continued development of the residuals approach, to support more accurate oscillation detection. Improved identification of oscillations could promote improved disease models and therapeutic technologies.

Reliability, costs, and radiation dose of dual-energy X-ray absorptiometry in diagnosis of radiologic sarcopenia in surgically menopausal women.

OBJECTIVE: The aim of this study was to evaluate and compare reliability, costs, and radiation dose of dual-energy X-ray absorptiometry (DXA) to MRI and CT in measuring muscle mass for the diagnosis of sarcopenia. METHODS: Thirty-four consecutive DXA scans performed in surgically menopausal women from November 2019 until March 2020 were analyzed by two observers. Observers analyzed muscle mass of the lower limbs in every scan twice. Reliability was assessed by calculating inter- and intra-observer variability. Reliability from CT and MRI as well as radiation dose from CT and DXA were collected from literature. Costs for each type of scan were calculated according to the guidelines for economic evaluation of the Dutch National Health Care Institute. RESULTS: The 34 participants had a median age of 58 years (IQR 53-65) and a median body mass index of 24.6 (IQR 21.7-29.7). Inter-observer variability had an intraclass correlation coefficient (ICC) of 0.997 (95% CI 0.994-0.998) with a relative variability of 0.037 ± 0.022%. Regarding intra-observer variability, observer 1 had an ICC of 0.998 (95% CI 0.996-0.999) with a relative variability of 0.019 ± 0.016% and observer 2 had an ICC of 0.997 (95% CI 0.993-0.998) with a relative variability of 0.016 ± 0.011%. DXA costs were €62, CT €77, and MRI €195. The estimated radiation dose of CT was 2.5-3.0 mSv, for DXA this was 2-4 µSv. CONCLUSIONS: DXA has lower costs and a lower radiation dose, with low inter- and intra-observer variability, compared to CT and MRI for assessing lower limb muscle mass. TRIAL REGISTRATION: Netherlands Trial Register; NL8068. CRITICAL RELEVANCE STATEMENT: DXA is a good alternative for CT and MRI in assessing lower limb muscle mass, with lower costs and lower radiation dose, while inter-observer and intra-observer variability are low. KEY POINTS: • Screening for sarcopenia should be optimized as the population ages. • DXA outperformed CT and MRI in the measured metrics. • DXA validity should be further evaluated as an alternative to CT and MRI for sarcopenia evaluation.

The National STD Curriculum Podcast as a Method to Increase STI Education for Health Care Professionals.

BACKGROUND: Podcasts are a valuable educational tool that are convenient and provide on-demand learning. We launched the National Sexually Transmitted Disease Curriculum (NSTDC) Podcast in 2020 to educate healthcare professionals on sexually transmitted infections (STIs) with an emphasis on content from peer-reviewed literature relevant to clinical practice. METHODS: We describe the reach and usage data for 31 podcast episodes produced during the first 29 months. Information was obtained via Google Analytics, Apple Podcasts, the podcast hosting platform Buzzsprout, and the Health Professional Application for Training form for listeners who were registered on the NSTDC website. RESULTS: There were more than 21,000 downloads, with an average of 686 downloads per episode. Although 85% of downloads occurred in the United States, podcast visitors were located in 57 countries. The three most reported professions/disciplines were registered nurse (39.0%), advanced practice nurse (22.5%), and physician (11.3%). Forty-eight percent of visitors had a primary programmatic focus of STDs, 24% HIV/AIDs, and 18% primary care. CONCLUSION: The NSTDC Podcast is a highly utilized resource for mobile and on-demand learning for health care professionals who want to expand their knowledge on STIs.

Lipid scrambling is a general feature of protein insertases.

Glycerophospholipids are synthesized primarily in the cytosolic leaflet of the endoplasmic reticulum (ER) membrane and must be equilibrated between bilayer leaflets to allow the ER and membranes derived from it to grow. Lipid equilibration is facilitated by integral membrane proteins called "scramblases." These proteins feature a hydrophilic groove allowing the polar heads of lipids to traverse the hydrophobic membrane interior, similar to a credit card moving through a reader. Nevertheless, despite their fundamental role in membrane expansion and dynamics, the identity of most scramblases has remained elusive. Here, combining biochemical reconstitution and molecular dynamics simulations, we show that lipid scrambling is a general feature of protein insertases, integral membrane proteins which insert polypeptide chains into membranes of the ER and organelles disconnected from vesicle trafficking. Our data indicate that lipid scrambling occurs in the same hydrophilic channel through which protein insertion takes place and that scrambling is abolished in the presence of nascent polypeptide chains. We propose that protein insertases could have a so-far-overlooked role in membrane dynamics as scramblases.

Sinonasal inverted papilloma and predictors of health-related quality of life after endonasal endoscopic surgery: A prospective cohort study.

OBJECTIVES: Existing knowledge on health-related quality of life (HRQoL) after surgical removal of sinonasal inverted papilloma (IP) is limited. Moreover, predictors for a better or worse post-operative HRQoL outcome are not known. Our aim was to assess HRQoL in all three health domains (physical, psychological, and social), track its post-operative trajectory, investigate if pre-operative observations could predict distinct post-operative HRQoL outcomes, and evaluate whether physicians' interventions could contribute to improved post-operative HRQoL. DESIGN: Prospective cohort study. SETTING: Tertiary referral hospital. PARTICIPANTS: Seventy-four patients who underwent surgery for an IP were included. They were asked to fill in the Endonasal Endoscopic Sinus and Skull-Base Surgery Questionnaire (EES-Q) pre-operatively, and then 2 weeks, 3 months, and 1 year post-operatively. MAIN OUTCOME MEASURES: Linear mixed models analyses were performed to evaluate the overall post-operative HRQoL and the separate health domains, as well as the impact of specific variables (sex, age, American Society of Anaesthesiologists [ASA] classification, smoker, Krouse staging, pre-operative EES-Q score, type of surgery, and post-operative antibiotics) on HRQoL improvement. RESULTS: The total EES-Q score (p < .001) as well as the physical (p < .001), psychological (p = .049), and the social (p = .002) domains significantly improved post-operatively. ASA classification (p = .049), pre-operative EES-Q score (p < .001) and post-operative antibiotics (p = .036) were significant variables. CONCLUSIONS: Overall HRQoL, as well as each of the three health domains, improved significantly. A higher ASA score, a higher pre-operative EES-Q score, and the administration of post-operative antibiotics were significant predictors for better HRQoL recovery post-operatively. Further research is necessary to confirm these results.

Outcome assessment methods of bioactive and biodegradable materials as pulpotomy agents in primary and permanent teeth: a scoping review.

BACKGROUND: Pulpotomy procedures aiming to preserve and regenerate the dentin-pulp complex have recently increased exponentially due to developments in the field of biomaterials and tissue engineering in primary and permanent teeth. Although the number of studies in this domain has increased, there is still scarcity of evidence in the current literature. OBJECTIVES: (1) Report the methods of outcome assessment of pulpotomy clinical trials in both primary and permanent teeth; (2) Identify the various bioactive agents and biodegradable scaffolds used in pulpotomy clinical trials in both primary and permanent teeth. MATERIALS AND METHODS: A scoping review of the literature was performed, including a search of primary studies on PubMed, Scopus, Web of Science, ProQuest and Clinicaltrials.gov. A search for controlled trials or randomized controlled trials published between 2012 and 2023 involving primary or permanent teeth receiving partial or full pulpotomy procedures using bioactive/regenerative capping materials was performed. RESULTS: 127 studies out of 1038 articles fulfilled all the inclusion criteria and were included in the current scoping review. More than 90% of the studies assessed clinical and radiographic outcomes. Histological, microbiological, or inflammatory outcomes were measured in only 9.4% of all included studies. Majority of the studies (67.7%) involved primary teeth. 119 studies used non-degradable bioactive cements, while biodegradable scaffolds were used by 32 studies, natural derivates and plant extracts studies were used in only 7 studies. Between 2012 (4 studies) and 2023 (11 studies), there was a general increase in the number of articles published. India, Egypt, Turkey, and Iran were found to have the highest total number of articles published (28, 28,16 and 10 respectively). CONCLUSIONS: Pulpotomy studies in both primary and permanent teeth relied mainly on subjective clinical and radiographic outcome assessment methods and seldom analyzed pulpal inflammatory status objectively. The use of biodegradable scaffolds for pulpotomy treatments has been increasing with an apparent global distribution of most of these studies in low- to middle-income countries. However, the development of a set of predictable outcome measures as well as long-term evidence from well conducted clinical trials for novel pulpotomy dressing materials are still required.

The yield of routine laboratory examination in osteoporosis evaluation in primary care.

This study evaluated the yield of routine laboratory examination in a large population of older women in primary care. The prevalence of laboratory abnormalities was low and the clinical consequences in follow-up were limited. There was a weak association of laboratory abnormalities with osteoporosis but no association with vertebral fractures and recent fractures. PURPOSE: Most osteoporosis guidelines advice routine laboratory examination. We have investigated the yield of laboratory examinations in facture risk evaluation of elderly women in primary care. METHODS: We assessed the prevalence of laboratory abnormalities and their association with risk factors for fractures, recent fractures, low bone mineral density (BMD), and prevalent vertebral fracture in 8996 women ≥ 65 years of age participating in a primary care fracture risk screening study. In a sample of 2208 of these participants, we also evaluated the medical consequences in the medical records during a follow-up period of ≥ 1 year. RESULTS: Vitamin D deficiency (< 30 nmol/L) was present in 13% and insufficiency (< 50 nmol/L) in 43% of the study sample. The prevalence of other laboratory abnormalities (ESR, calcium, creatinine, FT4) was 4.6% in women with risk factors for fractures, 6.1% in women with low BMD (T-score ≤ - 2.5), 6.0% after a prevalent vertebral fracture, 5.2% after a recent fracture and 2.6% in the absence of important risk factors for fractures. Laboratory abnormalities other than vitamin D were associated with low BMD (OR 1.4, 95%CI 1.1-1.8) but not with prevalent vertebral fractures nor recent fractures. Low BMD was associated with renal failure (OR 2.0, 95%CI 1.3-3.4), vitamin D insufficiency (OR 1.2, 95%CI 1.0-1.3) and deficiency (OR 1.3, 95%CI 1.1-.5). In the follow-up period, 82% of the laboratory abnormalities did not result in a new diagnosis or treatment reported in the medical records. CONCLUSIONS: We identified a low prevalence of laboratory abnormalities in a primary care population of older women and the majority of these findings had no medical consequences.

Challenges and lessons learned from a long-term postauthorisation safety study programme of rivaroxaban in Europe.

OBJECTIVES: To describe opportunities and challenges experienced from the four pharmacoepidemiological database studies included in the rivaroxaban post authorisation safety study (PASS) programme and propose ways to maximise the value of population-based observational research when addressing regulatory requirements. DESIGN: PASS programme of rivaroxaban carried out as part of the regulatory postapproval commitment to the European Medicines Agency. SETTING: Clinical practice in Germany, the Netherlands, Sweden and the UK (electronic health records)-undertaken by pharmacoepidemiology research teams using country-specific databases with different coding structures. PARTICIPANTS: 355 152 patients prescribed rivaroxaban and 338 199 patients prescribed vitamin K antagonists. RESULTS: Two major challenges that were encountered throughout the lengthy PASS programme were related to: (1) finalising country-tailored study designs before the extent of rivaroxaban uptake was known, and (2) new research questions that arose during the programme (eg, those relating to an evolving prescribing landscape). RECOMMENDATIONS: We advocate the following strategies to help address these major challenges (should they arise in any future PASS): conducting studies based on a common data model that enable the same analytical tools to be applied when using different databases; maintaining early, clear, continuous communication with the regulator (including discussing the potential benefit of studying drug use as a precursor to planning a safety study); consideration of adaptive designs whenever uncertainty exists and following an initial period of data collection; and setting milestones for the review of study objectives.

Influence of socioeconomic status on clinical outcomes of diffuse midline glioma and diffuse intrinsic pontine glioma.

OBJECTIVE: Given the lack of a definitive treatment and the poor prognosis of patients with diffuse midline glioma (DMG) and diffuse intrinsic pontine glioma (DIPG), socioeconomic status (SES) may affect treatment access and therefore survival. Therefore, this study aimed to examine the relationship between SES and treatment modalities, progression-free survival (PFS), and overall survival (OS) in children with DMG/DIPG. METHODS: A retrospective, single-institution review was conducted of medical records of patients ≤ 18 years of age who had DMG or DIPG that was diagnosed between 2000 and 2022. Patient demographics, surgical interventions, chemotherapy, radiation therapy, clinical trial enrollment, and medical care-related travel were extracted. SES variables (education and mean income) for associated patient census tracts were collected and stratified. Statistical analysis using unpaired t-tests, chi-square analysis, and log-rank tests was conducted. RESULTS: Of the 96 patients who met the inclusion criteria, the majority were female (59%) and non-Hispanic White (57%). The median PFS, median OS, and time from diagnosis to treatment did not differ between races/ethnicities or sex. Ninety-one of 96 patients had census tract data available. Patients from higher-income census tracts (> 50% of families with annual household income greater than $50,000) had a longer median OS (480 vs 235 days, p < 0.001) and traveled significantly longer distances for medical care (1550 vs 1114 miles, p = 0.048) than families from lower-income census tracts. Patients from the highest education quartile traveled significantly farther for treatment than the lowest education quartile (mean 2964 vs 478 miles, p = 0.047). Patients who received both oral and intravenous chemotherapy were more likely to be from higher-income census tracts than those who received intravenous or no chemotherapy. Duration of PFS, rates of clinical trial enrollment, biopsy rates, H3K27 mutation status, ventriculoperitoneal shunt placement rates, and radiotherapy rates were not associated with SES variables. CONCLUSIONS: Patients from families from higher-income census tracts experienced longer OS and traveled farther for treatment. Patients from families from higher-education-level census tracts traveled more often for treatment. The authors' findings suggest that SES influences DMG and DIPG OS. More studies should be done to understand the role of SES in the outcomes of children with DMG/DIPG.

A TBK1 variant causes autophagolysosomal and motoneuron pathology without neuroinflammation in mice.

Heterozygous mutations in the TBK1 gene can cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The majority of TBK1-ALS/FTD patients carry deleterious loss-of-expression mutations, and it is still unclear which TBK1 function leads to neurodegeneration. We investigated the impact of the pathogenic TBK1 missense variant p.E696K, which does not abolish protein expression, but leads to a selective loss of TBK1 binding to the autophagy adaptor protein and TBK1 substrate optineurin. Using organelle-specific proteomics, we found that in a knock-in mouse model and human iPSC-derived motor neurons, the p.E696K mutation causes presymptomatic onset of autophagolysosomal dysfunction in neurons precipitating the accumulation of damaged lysosomes. This is followed by a progressive, age-dependent motor neuron disease. Contrary to the phenotype of mice with full Tbk1 knock-out, RIPK/TNF-α-dependent hepatic, neuronal necroptosis, and overt autoinflammation were not detected. Our in vivo results indicate autophagolysosomal dysfunction as a trigger for neurodegeneration and a promising therapeutic target in TBK1-ALS/FTD.

Outcomes with the Adjustable Transobturator Male System (ATOMS) for the Treatment of Male Stress Urinary Incontinence After Prostate Surgery and the Impact of Previous Radiotherapy.

Background and objective: The adjustable transobturator male system (ATOMS) is an established treatment for patients with urinary incontinence after prostate surgery. Our objective was to evaluate the efficacy and the complication burdens associated with ATOMS with a focus on exploring the potential impact on previous radiotherapy (RT). Methods: We performed a retrospective analysis for consecutive patients who underwent ATMOS implantation procedure at a tertiary center over an 11-yr study period. Outcomes of interest were dryness at 3-mo follow up, postoperative complications (≤30 d), and late treatment failures (>30 d). Key findings and limitations: A total of 118 patients underwent ATOMS surgery performed by five different surgeons. Median follow-up was 67 mo (interquartile range 41-95). The mean 24-h pad count after surgery was 1.1 (range 0-8) and the mean reduction in pad weight was 179 g (range 0-1080). There was no significant difference in the reduction in pad use between groups with and without RT (-1.7 vs -2.4; p = 0.13). Multivariable analysis revealed that RT, degree of incontinence, and age were not risk factors for reoperation. Conclusions and clinical implications: ATOMS implantation is feasible in patients who have undergone prostate RT and patients with severe stress urinary incontinence after prostate surgery. We found that RT was not a risk factor for reoperation and there was no significant difference in pad weight reduction by RT status. This study offers new insight into potential incontinence surgery for male patients with stress urinary incontinence and previous RT. Patient summary: We assessed outcomes for patients who had an ATOMS (adjustable transobturator male system) device implanted to control stress urinary incontinence after prostate surgery. After implantation, 52.5% of the patients reported zero leakage and 39.9% reported only mild incontinence. Our results show that this device can improve continence after prostate surgery and is also suitable in patients who underwent radiotherapy.

Order effects in stimulus discrimination challenge established models of comparative judgement: A meta-analytic review of the Type B effect.

This paper provides a comprehensive review of the Type B effect (TBE), a phenomenon reflected in the observation that discrimination sensitivity varies with the order of stimuli in comparative judgment tasks, such as the two-alternative forced-choice (2AFC) paradigm. Specifically, when the difference threshold is lower (higher) with the constant standard preceding rather than following the variable comparison, one speaks of a negative (positive) TBE. Importantly, prominent psychophysical difference models such as signal detection theory (Green & Swets, 1966) cannot easily account for the TBE, and are hence challenged by it. The present meta-analysis provides substantial evidence for the TBE across various stimulus attributes, suggesting that the TBE is a general feature of discrimination experiments when standard and comparison are presented successively. Thus, inconsistent with psychophysical difference models, subjective differences between stimuli are not merely a function of their physical differences but rather also depend on their temporal order. From the literature, we identify four classes of potential candidate theories explaining the origin of the TBE, namely (1) differential weighting of the stimulus magnitudes at the two positions (e.g., Hellström, Psychological Research, 39, 345-388 1977), (2) internal reference formation (e.g., Dyjas, Bausenhart, & Ulrich, Attention, Perception, & Psychophysics, 74, 1819-1841 2012), (3) Bayesian updating (e.g., de Jong, Akyürek, & van Rijn, Psychonomic Bulletin and Review, 28, 1183-1190 2021), and (4) biased threshold estimation (García-Pérez & Alcalá-Quintana, Attention, Perception & Psychophysics, 72, 1155-1178 2010). As these models, to some extent, make differential predictions about the direction of the TBE, investigating the respective boundary conditions of positive and negative TBEs might be a valuable perspective for diagnostic future research.

Factors Associated With Use of the Preventive Health Inventory in US Veterans.

Importance: The COVID-19 pandemic caused significant declines in the quality of preventive and chronic disease care. The Veterans Health Administration (VHA) used the Preventive Health Inventory (PHI), a multicomponent care management intervention, to catch up on care disrupted by the pandemic. Objective: To identify key factors associated with PHI use. Design, Setting, and Participants: This cohort study of veterans receiving primary care used administrative data from national VHA primary care clinics for February 1, 2021, through February 1, 2022. Exposure: Patient PHI receipt. Main Outcomes and Measures: The main outcomes were patient, practitioner, and clinic factors associated with PHI receipt. Binomial generalized linear models with fixed effects for clinic were used to analyze factors associated with receipt of PHI. Least absolute shrinkage and selection operator procedures were used for variable selection. Results: A total of 4 358 038 veterans (mean [SD] age, 63.7 [16.0] years; 90% male; 76% non-Hispanic White) formed the study cohort, of whom 389 757 (9%) received the PHI. Veterans who received the PHI had higher mean Care Assessment Need (CAN) scores, which indicate the likelihood of hospitalization or death within 1 year (mean [SD], 51.9 [28.6] vs 47.2 [28.6]; standardized mean difference [SMD], -0.16). They were also more likely to live in urban areas (77% vs 64%; SMD, 0.28) and have a shorter drive distance to primary care (mean [SD], 13.2 [12.4] vs 15.7 [14.6] miles; SMD, 0.19). The mean outpatient use was higher among PHI recipients compared with non-PHI recipients (mean [SD], 18.4 [27.8] vs 15.1 [24.1] visits; SMD, -0.13). In addition, veterans with primary care practitioners with higher caseloads were more likely to receive the PHI (mean [SD], 778 [231] vs 744 [249] patients; SMD, -0.14), and they were more likely to be seen at larger clinics (mean [SD], 9670 [6876] vs 8786 [6892] patients; SMD, -0.13). Prior outpatient use and CAN score were associated with PHI receipt in the final model. Conclusions and Relevance: In this cohort study of the VHA's PHI, patients with higher CAN scores and more outpatient use in the previous year were more likely to receive the PHI. This study identifies potential intervention points to improve care coordination for veterans.

ST6GAL1 is associated with poor response to chemoradiation in rectal cancer.

INTRODUCTION: Colorectal cancer is the third most common cause of cancer death. Rectal cancer makes up a third of all colorectal cases. Treatment for locally advanced rectal cancer includes chemoradiation followed by surgery. We have previously identified ST6GAL1 as a cause of resistance to chemoradiation in vitro and hypothesized that it would be correlated with poor response in human derived models and human tissues. METHODS: Five organoid models were created from primary human rectal cancers and ST6GAL1 was knocked down via lentivirus transduction in one model. ST6GAL1 and Cleaved Caspase-3 (CC3) were assessed after chemoradiation via immunostaining. A tissue microarray (TMA) was created from twenty-six patients who underwent chemoradiation and had pre- and post-treatment specimens of rectal adenocarcinoma available at our institution. Immunohistochemistry was performed for ST6GAL1 and percent positive cancer cell staining was assessed and correlation with pathological grade of response was measured. RESULTS: Organoid models were treated with chemoradiation and both ST6GAL1 mRNA and protein significantly increased after treatment. The organoid model targeted with ST6GAL1 knockdown was found to have increased CC3 after treatment. In the tissue microarray, 42 percent of patient samples had an increase in percent tumor cell staining for ST6GAL1 after treatment. Post-treatment percent staining was associated with a worse grade of treatment response (p = 0.01) and increased staining post-treatment compared to pre-treatment was also associated with a worse response (p = 0.01). CONCLUSION: ST6GAL1 is associated with resistance to treatment in human rectal cancer and knockdown in an organoid model abrogated resistance to apoptosis caused by chemoradiation.

A new variant in the ZCCHC8 gene: diverse clinical phenotypes and expression in the lung.

Introduction: Pulmonary fibrosis is a severe disease which can be familial. A genetic cause can only be found in ∼40% of families. Searching for shared novel genetic variants may aid the discovery of new genetic causes of disease. Methods: Whole-exome sequencing was performed in 152 unrelated patients with a suspected genetic cause of pulmonary fibrosis from the St Antonius interstitial lung disease biobank. Variants of interest were selected by filtering for novel, potentially deleterious variants that were present in at least three unrelated pulmonary fibrosis patients. Results: The novel c.586G>A p.(E196K) variant in the ZCCHC8 gene was observed in three unrelated patients: two familial patients and one sporadic patient, who was later genealogically linked to one of the families. The variant was identified in nine additional relatives with pulmonary fibrosis and other telomere-related phenotypes, such as pulmonary arterial venous malformations, emphysema, myelodysplastic syndrome, acute myeloid leukaemia and dyskeratosis congenita. One family showed incomplete segregation, with absence of the variant in one pulmonary fibrosis patient who carried a PARN variant. The majority of ZCCHC8 variant carriers showed short telomeres in blood. ZCCHC8 protein was located in different lung cell types, including alveolar type 2 (AT2) pneumocytes, the culprit cells in pulmonary fibrosis. AT2 cells showed telomere shortening and increased DNA damage, which was comparable to patients with sporadic pulmonary fibrosis and those with pulmonary fibrosis carrying a telomere-related gene variant, respectively. Discussion: The ZCCHC8 c.586G>A variant confirms the involvement of ZCCHC8 in pulmonary fibrosis and short-telomere syndromes and underlines the importance of including the ZCCHC8 gene in diagnostic gene panels for these diseases.