Relationship between craniofacial skeletal patterns and anatomic characteristics of masticatory muscles: a systematic review and meta-analysis.

BACKGROUND: The anatomic characteristics of the masticatory muscles differ across craniofacial skeletal patterns. OBJECTIVE: To identify differences in the anatomic characteristics of masticatory muscles across different sagittal and vertical craniofacial skeletal patterns. ELIGIBILITY CRITERIA: Studies measuring the thickness, width, cross-sectional area (CSA), volume and orientation of masticatory muscles in healthy patients of different sagittal (Class I, Class II, and Class III) and/or vertical (normodivergent, hypodivergent, and hyperdivergent) patterns. INFORMATION SOURCES: Unrestricted literature searches in 8 electronic databases/registers until December 2023. RISK OF BIAS AND SYNTHESIS OF RESULTS: Study selection, data extraction, and risk of bias assessment with a customised tool were performed independently in duplicate. Random-effects meta-analysis and assessment of the certainty of clinical recommendations with the GRADE approach were conducted. RESULTS: 34 studies (37 publications) were selected with a total of 2047 participants and data from 16 studies were pulled in the meta-analysis. Masseter muscle thickness in relaxation was significantly greater by 1.14 mm (95% CI 0.74-1.53 mm) in hypodivergent compared to normodivergent patients while it was significantly decreased in hyperdivergent patients by - 1.14 mm (95% CI - 1.56 to - 0.73 mm) and - 2.28 mm (95% CI - 2.71 to - 1.85 mm) compared to normodivergent and hypodivergent patients respectively. Similar significant differences were seen between these groups in masseter muscle thickness during contraction as well as masseter muscle CSA and volume. Meta-analyses could not be performed for sagittal categorizations due to insufficient number of studies. CONCLUSIONS: Considerable differences in masseter muscle thickness, CSA and volume were found across vertical skeletal configurations being significantly reduced in hyperdivergent patients; however, results should be interpreted with caution due to the high risk of bias of the included studies. These variations in the anatomic characteristics of masticatory muscles among different craniofacial patterns could be part of the orthodontic diagnosis and treatment planning process. REGISTRATION: PROSPERO CRD42022371187 .

Quality-of-Life Outcomes from NRG/NSABP B-39/RTOG 0413: Whole-breast Irradiation vs Accelerated Partial-breast Irradiation after Breast Conserving Surgery.

PURPOSE: NRG Oncology (NRG)/NSABP B-39/RTOG 0413 compared whole-breast irradiation (WBI) to accelerated partial-breast irradiation (APBI). APBI was not equivalent to WBI in local tumor control. Secondary outcome was Quality-of-life (QOL). METHODS: The QOL sub-study used validated self-report questionnaires including the Breast Cancer Treatment Outcome Scale (BCTOS) and SF-36 vitality scale. Assessments occurred: before randomization, at treatment completion (chemotherapy or radiotherapy), 4-weeks later, at 6-, 12-, 24-, and 36-months. Primary aims: cosmesis change equivalency (baseline to 3 years; a priori margin of equivalence 0.4 standard deviations) and fatigue change superiority (baseline to end-of-treatment (EOT)) for APBI vs WBI, by patient groups treated with or without chemotherapy when appropriate. RESULTS: From 3/21/05-5/25/09, 975 patients enrolled in this sub-study; 950 had follow-up data. APBI had 3-year cosmesis equivalent to WBI (95%CI,-0.0001-0.16; equivalence margin -0.22-0.22) in all patients. The APBI group without chemotherapy had less EOT fatigue (p = .011; mean score APBI 63 vs WBI 59); APBI group receiving chemotherapy had worse EOT fatigue (p = .011; APBI 43 vs WBI 49). The APBI group reported less pain (BCTOS) at EOT (WBI 2.29 vs APBI 1.97), but worse pain at 3-years (WBI 1.62 vs APBI 1.71). APBI patients reported greater convenience of care than with WBI and reported less symptom severity at EOT and 4-weeks later. CONCLUSION: Cosmetic outcomes were similar for APBI and WBI groups, with small statistically significant differences in other outcomes that varied over time. Differences in fatigue and other symptoms appeared to resolve by ≥ 6 months. APBI may be preferred by some patients, for whom extended treatment is burdensome.

HAF prevents hepatocyte apoptosis and progression to MASH and hepatocellular carcinoma through transcriptional regulation of the NF-κB pathway.

BACKGROUND: HCC incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction-associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways driving MASH-HCC are poorly understood. We have previously reported that male mice with haploinsufficiency of hypoxia-associated factor, HAF (SART1+/-) spontaneously develop MASH-HCC. However, the cell type(s) responsible for HCC associated with HAF loss are unclear. RESULTS: We generated SART1-floxed mice, which were crossed with mice expressing Cre-recombinase within hepatocytes (Alb-Cre; hepS-/-) or myeloid cells (LysM-Cre, macS-/-). HepS-/- mice (both male and female) developed HCC associated with profound inflammatory and lipid dysregulation suggesting that HAF protects against HCC primarily within hepatocytes. HAF-deficient hepatocytes showed decreased P-p65 and P-p50 and in many components of the NF-κB pathway, which was recapitulated using HAF siRNA in vitro. HAF depletion also triggered apoptosis, suggesting that HAF protects against HCC by suppressing hepatocyte apoptosis. We show that HAF regulates NF-κB activity by regulating transcription of TRADD and RIPK1. Mice fed a high-fat diet (HFD) showed marked suppression of HAF, P-p65 and TRADD within their livers after 26 weeks, but showed profound upregulation of these proteins after 40 weeks, implicating deregulation of the HAF-NF-κB axis in the progression to MASH. In humans, HAF was significantly decreased in livers with simple steatosis but significantly increased in HCC compared with normal liver. CONCLUSIONS: HAF is novel transcriptional regulator of the NF-κB pathway and is a key determinant of cell fate during progression to MASH and MASH-HCC.

Center of mass states render multi-joint torques throughout standing balance recovery.

Successful reactive balance control requires coordinated modulation of hip, knee, and ankle torques. Stabilizing joint torques arise from feedforward neural signals that modulate the musculoskeletal system's intrinsic mechanical properties, namely muscle short-range stiffness, and neural feedback pathways that activate muscles in response to sensory input. Although feedforward and feedback pathways are known to modulate the torque at each joint, the role of each pathway to the balance-correcting response across joints is poorly understood. Since the feedforward and feedback torque responses act at different delays following perturbations to balance, we modified the sensorimotor response model (SRM), previously used to analyze the muscle activation response to perturbations, to consist of parallel feedback loops with different delays. Each loop within the model is driven by the same information, center of mass (CoM) kinematics, but each loop has an independent delay. We evaluated if a parallel loop SRM could decompose the reactive torques into the feedforward and feedback contributions during balance-correcting responses to backward support surface translations at four magnitudes. The SRM accurately reconstructed reactive joint torques at the hip, knee, and ankle, across all perturbation magnitudes (R 2 >0.84 & VAF>0.83). Moreover, the hip and knee exhibited feedforward and feedback components, while the ankle only exhibited feedback components. The lack of a feedforward component at the ankle may occur because the compliance of the Achilles tendon attenuates muscle short-range stiffness. Our model may provide a framework for evaluating changes in the feedforward and feedback contributions to balance that occur due to aging, injury, or disease. NEWS AND NOTEWORTHY: Reactive balance control requires coordination of neurally-mediated feedforward and feedback pathways to generate stabilizing joint torques at the hip, knee, and ankle. Using a sensorimotor response model, we decomposed reactive joint torques into feedforward and feedback contributions based on delays relative to center of mass kinematics. Responses across joints were driven by the same signals, but contributions from feedforward versus feedback pathways differed, likely due to differences in musculotendon properties between proximal and distal muscles.

Genetic parameters for egg quality traits in Pekin ducks.

Pekin duck (Anas platyrhynchos domesticus) is the most widely consumed duck protein with nearly 35 million animals produced annually in the United States and exported worldwide. Pekin ducks are primarily utilized in meat production, so very little information is available about their heritability estimates and genetic correlations for traits related to egg quality. Genetically improving duck populations together with the implementation of more efficient nutritional and management strategies is paramount for the long-term sustainability of the US duck industry. There is a potential opportunity to increase meat duck productivity by improving hatching egg quality. The main objectives of this study were to estimate heritability and genetic correlations for various egg quality traits in a commercial population of Pekin ducks. Egg quality traits for 612 Pekin duck females were measured through 3 time points over 2 generations (GEN) [30, 32, and 35 wk of age (WOA)]. GEN 2 had an additional sampling occurring at 40 WOA. Genetic correlations and heritability estimates were calculated for all the traits using the BLUPF90 software, the Restricted Maximum Likelihood (REML) method, and a pedigree containing 9,418 individuals. All egg quality traits evaluated are moderately to highly heritable ranging from 0.20 for Haugh Unit (HU) and Vitelline Membrane Strength (VMS) to 0.71 for shell ratio (SR). Heritability estimates were calculated for each age of collection and in general heritability increased up to 35 WOA. Genetic correlations between egg quality traits showed a wide range of positive and negative relationships with correlation strengths ranging of -0.80 [yolk ratio (YR) and albumin ratio (AR)] to 0.99 [egg volume (EV) and egg weight (EW)]. The results of this study highlight the potential to improve hatching egg quality within Pekin ducks using a multi-trait selection scheme through direct genetic selection.

Unraveling the genomic diversity and admixture history of captive tigers in the United States.

Genomic studies of endangered species have primarily focused on describing diversity patterns and resolving phylogenetic relationships, with the overarching goal of informing conservation efforts. However, few studies have investigated genomic diversity housed in captive populations. For tigers (Panthera tigris), captive individuals vastly outnumber those in the wild, but their diversity remains largely unexplored. Privately owned captive tiger populations have remained an enigma in the conservation community, with some believing that these individuals are severely inbred, while others believe they may be a source of now-extinct diversity. Here, we present a large-scale genetic study of the private (non-zoo) captive tiger population in the United States, also known as "Generic" tigers. We find that the Generic tiger population has an admixture fingerprint comprising all six extant wild tiger subspecies. Of the 138 Generic individuals sequenced for the purpose of this study, no individual had ancestry from only one subspecies. We show that the Generic tiger population has a comparable amount of genetic diversity relative to most wild subspecies, few private variants, and fewer deleterious mutations. We observe inbreeding coefficients similar to wild populations, although there are some individuals within both the Generic and wild populations that are substantially inbred. Additionally, we develop a reference panel for tigers that can be used with imputation to accurately distinguish individuals and assign ancestry with ultralow coverage (0.25×) data. By providing a cost-effective alternative to whole-genome sequencing (WGS), the reference panel provides a resource to assist in tiger conservation efforts for both ex- and in situ populations.

The 2023 South Sudanese outbreak of Hepatitis E emphasizes ongoing circulation of genotype 1 in North, Central, and East Africa.

In April 2023, an outbreak of acute hepatitis was reported amongst internally displaced persons in the Nazareth community of South Sudan. IgM serology-based screening suggested the likely etiologic agent to be Hepatitis E virus (HEV). In this study, plasma specimens collected from anti-HEV IgM-positive cases were subjected to additional RT-qPCR testing and sequencing of extracted nucleic acids, resulting in the recovery of five full and eight partial HEV genomes. Maximum likelihood phylogenetic reconstruction confirmed the genomes belong to HEV genotype 1. Using distance-based methods, we show that genotype 1 is best split into three sub-genotypes instead of the previously proposed seven, and that these sub-genotypes are geographically restricted. The South Sudanese sequences confidently cluster within sub-genotype 1e, endemic to northeast, central, and east Africa. Bayesian Inference of phylogeny incorporating sampling dates shows that this new outbreak is not directly descended from other recent local outbreaks for which sequence data is available. However, the analysis suggests that sub-genotype 1e has been consistently and cryptically circulating locally for at least the past half century and that the known outbreaks are often not directly descended from one another. The ongoing presence of HEV, combined with poor sanitation and hygiene in the conflict-affected areas in the region, place vulnerable populations at risk for infection and its more serious effects, including progression to fulminant hepatitis.

Self-reported chronic therapy use after 24-weeks of follow-up by participants who completed the simplify randomized, controlled trial.

BACKGROUND: Highly effective CFTR modulator therapy (HEMT) has improved the health of many people with cystic fibrosis (pwCF), offering opportunities to discontinue burdensome therapies. SIMPLIFY included randomized, controlled trials that confirmed non-inferiority of discontinuing versus continuing dornase alfa (DA) or hypertonic saline (HS) for 6 weeks in pwCF on HEMT. In this study of post-trial treatment use by SIMPLIFY participants, we hypothesized that randomization to discontinue DA or HS during the trial would be associated with a higher likelihood of non-use of each medication during follow-up. METHODS: We electronically surveyed SIMPLIFY participants every 4 weeks for 24 weeks after trial completion but before the main trial results were publicly disclosed. We asked them how often they used medications during the previous week. We estimated covariate-adjusted odds ratios (ORs) of DA or HS non-use by logistic regression with generalized estimating equations. RESULTS: After exclusions mostly due to lack of any surveys, 472 participants were included in the analysis population, 181 from the HS trial and 291 from the DA trial. Approximately half of the analysis population completed all six surveys. At every month of follow-up in both trials, the percentage of individuals reporting non-use of DA or HS during the previous week was greater among those randomized to discontinue therapy. Among participants with responses at 24 weeks, 30/122 (24.6 %) in the HS trial and 79/222 (35.6 %) in the DA trial reported non-use of the respective study medication. After adjusting for covariates, participants randomized to discontinue DA were 8.7-times (95 % CI: 4.3-17.7) more likely to not use DA during follow-up than those randomized to continue DA, and participants randomized to discontinue HS were 5.2-times (95 % CI: 2.1-12.8) more likely to not use HS during follow-up compared to those randomized to continue. CONCLUSIONS: In healthy pwCF on ETI, randomization to discontinue DA or HS during SIMPLIFY was associated with greater odds of not using each medication after the trial compared to randomization to continue. These findings suggest that participation in a treatment discontinuation trial can influence participants' post-trial treatment decisions. This possibility may be relevant during discussions about research participation and clinical care.

Association of Resilience-Related Life Experiences on Variability on Age of Onset in Dominantly Inherited Alzheimer Disease.

BACKGROUND AND OBJECTIVES: It remains unknown whether the associations between protective lifestyles and sporadic dementia risk reported in observational studies also affect age at symptom onset (AAO) in autosomal dominant Alzheimer disease (ADAD) with predominant genetic influences. We investigated the associations between resilience-related life experiences and interindividual AAO variability in ADAD. METHODS: We performed a longitudinal and confirmatory analysis of the Dominantly Inherited Alzheimer Network prospective observational cohort (January 2009-June 2018, follow-up duration 2.13 ± 2.22 years), involving clinical, CSF, and lifestyle/behavioral assessments. We performed a 2-pronged comprehensive resilience assessment in each cohort. Cohort 1, incorporating the general resilience definition (cognitive maintenance [Clinical Dementia Rating = 0] despite high pathology), included carriers during the periods of significant CSFp-tau181 variability and grouped into resilience/resistance outcome bins according to the dichotomous pathologic and cognitive statuses, subcategorized by the estimated years from expected symptom onset (EYO). Cohort 2, focused on ADAD-specific genetically determined time frame characterizing the onset predictability, included asymptomatic participants with available preclinical lifestyle data and AAO outcomes and grouped into delayed or earlier AAO relative to the parental AAO. Associations of cognitive, CSFp-tau181, and lifestyle/behavioral predictors with binary outcomes were investigated using logistic regression. RESULTS: Of 320 carriers (age 38.19 ± 10.94 years, female 56.25%), cohort 1 included 218 participants (39.00 ± 9.37 years, 57.34%) and cohort 2 included 28 participants (43.34 ± 7.40 years, 71.43%). In cohort 1, 218 carriers after -20 EYO, when the interindividual variability (SD) of CSFp-tau181 first became more than twice greater in carriers than in noncarriers, were grouped into low-risk control (asymptomatic, low pathology, n = 103), high-resilience (asymptomatic despite high pathology, n = 60), low-resilience (symptomatic despite low pathology, n = 15), and susceptible control (symptomatic, high pathology, n = 40) groups. Multivariable predictors of high resilience, controlling for age and depression, included higher conscientiousness (odds ratio 1.051 [95% CI 1.016-1.086], p = 0.004), openness to experience (1.068 [1.005-1.135], p = 0.03) (vs. susceptible controls), and agreeableness (1.082 [1.015-1.153], p = 0.02) (vs. low resilience). From 1 to 3 years before parental AAO (cohort 2), the multivariable predictor of delayed AAO, controlling for CSFp-tau181, was higher conscientiousness (0.916 [0.845-0.994], p = 0.036). DISCUSSION: Among the cognitively and socially integrated life experiences associated with resilience, measures of conscientiousness were useful indicators for evaluating resilience and predicting future dementia onset in late preclinical ADAD.

A prospective longitudinal investigation of the trajectory of obsessive-compulsive symptoms during adolescence.

Obsessive-compulsive symptoms (OCS) increase with age during childhood and adolescence, and subthreshold OCS in childhood associate with a higher probability of obsessive-compulsive disorder (OCD) diagnosis in adulthood. Additionally, average age of onset for OCD is in adolescence, with the majority of OCD cases emerging by early adulthood. Despite these trends, the specific course of OCS development in adolescence is relatively unknown. To this end, the present prospective longitudinal study used latent growth mixture modeling and a diverse community sample of 3,335 high schoolers to identify and characterize growth trajectories of OCS across middle to late adolescence. Results identified three trajectories: High-but-Remitting, Moderate-but-Escalating, and Low-and-Stable. Results also indicated age, gender, anxiety sensitivity, and distress tolerance as significant predictors of trajectory group membership, such that younger age and being female predicted classification in the High-but Remitting group, greater anxiety sensitivity predicted classification in both the High-but-Remitting and Moderate-but Escalating groups, and greater distress tolerance predicted a lower likelihood of classification in the High-but-Remitting and Moderate-but-Escalating groups. Taken together, these trajectories have illustrated the temporal course and development of OCS across key developmental years. Moreover, the trajectories and their corresponding predictors may help identify adolescents who are particularly vulnerable to developing OCD.

Four-dimensional endocardial surface imaging with dynamic virtual reality rendering: a technical note.

Open heart surgery requires a proper understanding of the endocardial surface of the heart and vascular structures. While modern four-dimensional (4D) imaging enables excellent dynamic visualization of the blood pool, endocardial surface anatomy has not routinely been assessed. 4D image data were post-processed using commercially available virtual reality (VR) software. Using thresholding, the blood pool was segmented dynamically across the imaging volume. The segmented blood pool was further edited for correction of errors due to artifacts or inhomogeneous signal intensity. Then, a surface shell of an even thickness was added to the edited blood pool. When the cardiac valve leaflets and chordae were visualized, they were segmented separately using a different range of signal intensity for thresholding. Using an interactive cutting plane, the endocardial surface anatomy was reviewed from multiple perspectives by interactively applying a cutting plane, rotating and moving the model. In conclusions, dynamic three-dimensional (3D) endocardial surface imaging is feasible and provides realistic simulated views of the intraoperative scenes at open heart surgery. As VR is based on the use of all fingers of both hands, the efficiency and speed of postprocessing are markedly enhanced. Although it is limited, visualization of the cardiac valve leaflets and chordae is also possible.

Can combining existing behavioral tools improve identification of infants at elevated likelihood of autism in the first year of life?

LAY ABSTRACT: Many families have concerns about their infants' development in the first year of life. Current screeners cannot tell whether these differences might be related to autism, developmental delays, or likely to resolve on their own. As a result, many families are told to "wait and see." In this study, we looked at whether combining multiple behavior measures can improve prediction of outcomes in toddlerhood. This could help to provide families with more information about the significance of early behavioral differences. We assessed 256 infants with an older autistic sibling at 6, 9, and 12 months. We created three markers of behavioral differences at these ages. We looked at whether infants who had two or more markers were more likely to be on the autism spectrum or have other developmental differences than to have typically developing outcomes at 36 months. We found that very few infants had more than one marker at any age. However, infants who showed two or more markers were more likely to be on the spectrum or have other developmental differences at 36 months than infants who showed only one marker. These findings suggest that when behavioral differences are present on multiple measures, there is no need to wait and see before referring for services.

A Lifecourse Perspective on Singlehood.

A growing number of adults are spending more of their lifetime as single, either because they are taking longer to form unions, are re-entering singlehood after the dissolution of unions, or are avoiding union formation all together. Nevertheless, existing relationship research still generally positions singlehood as something to avoid, limiting our understanding of the rapidly evolving position of singlehood within the lifecourse as well as its implications for health and well-being. Thus, this special issue includes four articles that collectively offer theoretical and empirical inquiries of developmental and historical trends in singlehood and relationship histories, examine the antecedents and consequences of these trends, and explore how they vary based on salient sociodemographic characteristics. Overall, this special issue demonstrates that singlehood is more than just a temporary status within one's "progression" to the formation of committed relationships. It is our hope that the papers in this issue will encourage scholars to revise and expand their perspective on relationships to include singlehood alongside committed relationships as a potentially viable and healthy status as well as valid point of destination.

Mediators of racial/ethnic inequities in clinical trial participation among patients with cancer, 2011-2023.

BACKGROUND: While minoritized populations are less likely to participate in cancer trials, it is unknown whether social determinants of health (SDOH) explain these inequities. Here we identify SDOH factors that contribute to racial/ethnic inequities in clinical trial participation among patients with 22 common cancers. METHODS: This retrospective cohort study used electronic health record data (2011-2023) linked to neighborhood (Census tract) data from multiple sources. Patients were followed from diagnosis to clinical study drug receipt (proxy for trial participation), death, or last recorded activity. Associations were assessed using Cox proportional hazards models adjusted for clinical factors (diagnosis year, age, sex, performance status, stage, cancer type). To elucidate which area-level SDOH underlie racial/ethnic inequities, mediation analysis was performed using nonlinear multiple additive regression tree models. RESULTS: This study included 250105 patients (64.7% non-Latinx White, 8.9% non-Latinx Black, 5.2% Latinx). Black and Latinx patients were more likely to live in economically/socially marginalized areas (eg, disproportionately minoritized [measure of segregation], limited English proficiency [LEP], low vehicle ownership) than White patients. Black (3.7%; HR = 0.55 [CI = 0.52-0.60]) and Latinx patients (4.4%; HR = 0.63 [CI = 0.58-0.69]) were less likely to participate in trials than White patients (6.3%). Fewer patients in economically/socially marginalized neighborhoods participated in trials. Mediators explained 62.2% (CI = 49.5%-74.8%) of participation inequities between Black and White patients; area-level SDOH-including segregation (29.9% [CI = 21.2%-38.6%]) and vehicle ownership (11.6% [CI = 7.0%-16.1%])-were the most important mediators. Similarly, Latinx-White participation inequities were mediated (65.1%, [CI = 49.8%-80.3%]) by area-level SDOH such as segregation (39.8% [CI = 28.3%-51.3%]), LEP (11.6%, [CI = 2.8%-20.4%]), and vehicle ownership (9.6% [CI = 5.8%-13.5%]). CONCLUSIONS: To improve racial/ethnic diversity in cancer trials, efforts to address barriers related to adverse neighborhood SDOH factors are necessary.

Deep Brain Ultrasound Ablation Thermal Dose Modeling with in Vivo Experimental Validation.

Intracorporeal needle-based therapeutic ultrasound (NBTU) is a minimally invasive option for intervening in malignant brain tumors, commonly used in thermal ablation procedures. This technique is suitable for both primary and metastatic cancers, utilizing a high-frequency alternating electric field (up to 10 MHz) to excite a piezoelectric transducer. The resulting rapid deformation of the transducer produces an acoustic wave that propagates through tissue, leading to localized high-temperature heating at the target tumor site and inducing rapid cell death. To optimize the design of NBTU transducers for thermal dose delivery during treatment, numerical modeling of the acoustic pressure field generated by the deforming piezoelectric transducer is frequently employed. The bioheat transfer process generated by the input pressure field is used to track the thermal propagation of the applicator over time. Magnetic resonance thermal imaging (MRTI) can be used to experimentally validate these models. Validation results using MRTI demonstrated the feasibility of this model, showing a consistent thermal propagation pattern. However, a thermal damage isodose map is more advantageous for evaluating therapeutic efficacy. To achieve a more accurate simulation based on the actual brain tissue environment, a new finite element method (FEM) simulation with enhanced damage evaluation capabilities was conducted. The results showed that the highest temperature and ablated volume differed between experimental and simulation results by 2.1884°C (3.71%) and 0.0631 cm3 (5.74%), respectively. The lowest Pearson correlation coefficient (PCC) for peak temperature was 0.7117, and the lowest Dice coefficient for the ablated area was 0.7021, indicating a good agreement in accuracy between simulation and experiment.

Mapping coexisting hotspots of multidimensional food market (in)accessibility and climate vulnerability.

With the increasing likelihood of agricultural production failures under a warmer global climate, the importance of markets in providing access to nutrient-dense foods (NDFs) through trade is predicted to grow. However, regions with relatively poor access to markets and supporting infrastructures (e.g. roads and storage facilities) are potentially ill-equipped to deal with both short-term hydrometeorological hazards such as droughts and floods, and longer-term shifts in agricultural productivity. Despite the increasing focus upon markets within academic and policymaking circles, a regional-scale assessment of these potentially coexisting hotspots of vulnerability has not been conducted. We conduct a two-stage geospatial analysis integrating three publicly available datasets across the Indian states of Bihar, Chhattisgarh, Jharkhand, and Odisha. Combining the 2011 national census with the new PMGSY-GeoSadak database, we conduct nearest neighbour analysis to measure multidimensional market inaccessibility by: (i) distance from a settlement to its nearest village, town or city with a market, (ii) distance from a settlement to its nearest major road, and (iii) distance from a settlement to its subdistrict headquarters. We then correlate these measures with India's only district-wise assessment of climate vulnerability to identify hotspots of market inaccessibility and climate hazards. We find that the three market access measures are spatially autocorrelated and positively interrelated at the settlement (n = 129 555) and district (n = 107) levels, meaning that settlements located further from their nearest market tend to experience poorer road connectivity and access to the subdistrict economic hub. Approximately 18.5-million people live in districts with relatively high climate vulnerability and relatively high and multidimensional market inaccessibility. Hotspots of coexisting vulnerabilities are also disproportionately populated by 'Schedule Castes and Schedule Tribes' (SC/ST) communities. The identification of coexisting hotspots has important implications for the development of equitable and resilient markets that bolster NDF access for climate vulnerable and nutritionally insecure populations.

The effect of occlusal loading on secondary tooth eruption: An experimental study using a rat model.

This study aimed to assess the impact of occlusal loading on secondary tooth eruption and to determine the extent to which altering the occlusal loading influences the magnitude of secondary eruption through an experimental rat model. The present sample consisted of 48 male Wistar rats. At the onset of the experiment, 24 rats were 4 weeks old (young rats) and 24 rats were 26 weeks old (adult). Within each age group, the rats were further divided into two equal subgroups (12 rats each), receiving either a soft- or hard-food diet for the 3-month duration of the experiment. The primary outcome was the tooth position changes relative to stable references in the coronal plane by evaluating the distance between the mandibular first molars and the inferior alveolar canal. Microcomputed tomography scans were taken from all rats at three standardized intervals over the 3-month study period. Descriptive statistics were calculated by age and diet over time, and the evolution of the outcomes were plotted by age and diet over time. Longitudinal data analysis via generalized estimating equations was performed to examine the effect of age, diet and time on the primary outcomes. Secondary tooth eruption was observed in all age groups (young and adult) regardless of diet consistency (soft or hard food). In young rats, the secondary eruption was greater in the animals fed a soft diet than those fed a hard diet. In adult rats, minimal difference in secondary tooth eruption were found between different diet consistencies. Occlusal loading influences secondary tooth eruption in teeth with an established occlusal contact. The quantity of eruption in growing rats is higher when occlusal loading is less, providing a certain amount of secondary tooth eruption occurs. This difference, however, is not evident in adult rats, at least during the given 3-month time frame.

The Impact of Endplate Coverage on Heterotopic Ossification Following Cervical Disc Replacement: A Systematic Review and Meta Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Describe the impact of endplate coverage on HO in Cervical disc replacement (CDR). SUMMARY OF BACKGROUND DATA: CDR is a motion-sparing alternative to anterior cervical discectomy and fusion. However, the high prevalence of heterotopic ossification threatens to diminish range of motion and limit this benefit associated with CDR. METHODS: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. EMBASE and PubMed databases were queried. Results were deduplicated and screened. Relevant studies were included. All metrics that were reported in ≥3 studies were aggregated for analysis. SPSS was used to perform the meta-analysis. RESULTS: A total of 10 studies were included in the systematic review. Endplate coverage was assessed using a wide variety of measurements, including anteroposterior implant depth (ID), endplate depth (ED), exposed endplate depth (EED), implant depth to endplate depth ratio (ID:ED), EED to ED ratio (EED:ED), implant width (IW) to endplate width (EW) ratio (IW:EW), and the implant area (IA) to endplate area (EA) ratio (IA:EA). No evidence has linked ID (3 studies) to HO. Mixed evidence has linked ID:ED (3/5) and IW:ED (1/2) to HO. All available evidence has linked ED (2), EED (4), EED:ED (2), and IA:EA (1) to HO. In our meta-analysis, ID was not found to be a significant risk factor for HO. However, EED and ID:ED were found to be significant risk factors for HO formation. CONCLUSIONS: Exposed endplate, especially as assessed by EED and ID:ED, is a significant risk factor for HO. Surgeons should focus on preoperative planning and intraoperative implant selection to maximize endplate coverage. While optimizing technique and implant selection is crucial, improved implant design may also be necessary to ensure that appropriate implant-endplate footprint matching is possible across the anatomic spectrum.

Development of a sensitive LC-MS/MS assay to support human microdose study for an oral agonist of the GLP-1 receptor.

Aim: The purpose of this work was to determine the feasibility of supporting a clinical microdose study for PF-06882961 (danuglipron), an oral small molecule agonist of the GLP-1 receptor, by LC-MS/MS. Methodology: Statistical instrument parameter optimization using response surface methodology was employed to develop a LC-MS/MS method for the analyte, PF-06882961. Results: An LC-MS/MS method was developed and validated to support a proof of concept microdose pharmacokinetics preclinical study in monkeys, administered PF-06882961 (0.005 mg total, average dose = 0.0007 mg/kg) via intravenous bolus injection. Conclusion: The present study demonstrated the feasibility of analyzing human microdose plasma samples for PF-06882961 by LC-MS/MS, instead of accelerator mass spectrometry, thereby reducing cost and eliminating synthesis and exposure to 14C labeled material.

[Box: see text].

Tibial Spine Avulsion Fracture Fixation Using a Re-tensionable All-Suture Construct.

Tibial spine avulsion injuries, including fractures, are a variant of anterior cruciate ligament injuries. Treatment historically consisted of open reduction and internal fixation of the avulsion fracture, with anterior cruciate ligament reconstruction considered in cases of failed open reduction and internal fixation or residual laxity. However, improved instrumentation has led to the advancement of various arthroscopic techniques for addressing these injuries. The emergence of newer implants designed for all-suture fixation has also overcome the limitations associated with screw fixation, such as hardware-related complications, challenges in treating comminuted fractures, and potential physeal injury. The purpose of this article is to describe a technique consisting of arthroscopic-assisted reduction and internal fixation of a tibial spine avulsion fracture with a re-tensionable all-suture-based construct using multiple looped cinch stitches and a cortical suspensory suture button device.