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Purpose: To design, manufacture, and validate a female pelvic phantom for multi‐modality imaging (CT, MRI, US) to benchmark a commercial needle tracking system with application in HDR gynecological (GYN) interstitial procedures. Materials and Methods: A GYN needle‐tracking phantom was designed using CAD software to model an average uterus from a previous patient study, a vaginal canal from speculum dimensions, and a rectum to accommodate a transrectal ultrasound (TRUS) probe. A target volume (CTVHR) was designed as an extension from the cervix‐uterus complex. Negative space molds were created from modeled anatomy and 3D printed. Silicone was used to cast the anatomy molds. A 3D printed box was constructed to house the manufactured anatomy for structural integrity and to accommodate the insertion of a speculum, tandem, needles, and TRUS probe. The phantom was CT‐imaged to identify potential imperfections that might impact US visualization. Free‐hand TRUS was used to guide interstitial needles into the phantom. The commercial tracking system was used to generate a 3D US volume. After insertion, the phantom was imaged with CT and MR and the uterus and CTVHR dimensions were verified against the CAD model. Results/Conclusions: The manufactured phantom allows for accurate visualization with multiple imaging modalities and is conducive to applicator and needle insertion. The phantom dimensions from the CAD model were verified with those from each imaging modality. The phantom is low cost and can be reproducibly manufactured with the 3D printing and molding processes. Our initial experiments demonstrate the ability to integrate the phantom with a commercial tracking system for future needle tracking validation studies. [ABSTRACT FROM AUTHOR]

The practical application of embryo transfer in pigs could benefit from using embryo donors for multiple cycles. Thus, raising the need to investigate feeding strategies for donors which will not be required to recover body condition lost during previous lactation. The objective was to evaluate the effects of temporary feed restriction, from d 6 to 14 of the estrous cycle, on growth, blood variables and reproductive performance in replacement gilts. Replacement gilts (n = 20; TN70, Topigs Norsvin, Oak Bluff, Canada) were assigned equally across 2 feeding regimens following a randomized complete block design where the block was backfat thickness. The feeding regimens were based on the first day of the estrous cycle: CON, recommended feeding levels from d 0 to 14 and a flush feeding (25% above recommended levels) from d 15 until d 21; or RES, CON but with restricted feeding (25% below recommended levels) from d 6 to 14. The CON treatment was based on the recommendations of the Feed Manual TN70 (Topigs Norsvin, 2015). On d 0, 5, 14 and 20 of the cycle, body weight and backfat thickness were measured. On d 21 (detected estrus), gilts were inseminated and on d 27 they were euthanized to collect embryos, ovaries and uterus. The uterus and ovaries were weighed whereas corpora lutea were counted and weighed. Blood serum was collected on d 14, and 20 for chemical analyses. Data were analyzed using the mixed procedure of SAS where each gilt was the experimental unit. Feeding regimens were considered as the fixed effect and backfat block as the random effect. Means were obtained with the LSMEANS statement. No differences (P > 0.05) were observed on growth performance among feeding regimens. However, when comparing the average daily gain (ADG) within feeding regimens between feeding periods, no differences (P > 0.05) were observed among gilts fed CON whereas gilts fed RES showed a decreased (P < 0.05) ADG during d 6 to 14 compared with d 0 to 5 and d 15 to 21. Regarding blood serum variables, gilts fed RES had greater (P < 0.05) total protein and potassium but less (P < 0.05) sodium-to-potassium ratio than gilts fed CON on d 14. On d 20, Gilts fed RES had greater (P < 0.05) cholesterol values than gilts fed CON. No differences (P > 0.05) were observed on the number of corpora lutea, number of embryos collected or on collection efficiency. Similarly, no differences (P > 0.05) were observed on the weight of reproductive organs or on measurements of ovaries among feeding regimens. In conclusion, restricting feed intake of replacement gilts by 25% of the recommendation from d 6 to 14 of the estrous cycle reduced ADG without compromising their reproductive performance. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) and machine learning (ML) have resulted in significant enthusiasm for their promise in healthcare. Despite this, prospective randomized controlled trials and successful clinical implementation remain limited. One clinical application of ML is mitigation of the increased risk for acute care during outpatient cancer therapy. We previously reported the results of the System for High Intensity EvaLuation During Radiation Therapy (SHIELD-RT) study (NCT04277650), which was a prospective, randomized quality improvement study demonstrating that ML based on electronic health record (EHR) data can direct supplemental clinical evaluations and reduce the rate of acute care during cancer radiotherapy with and without chemotherapy. The objective of this study is to report the workflow and operational challenges encountered during ML implementation on the SHIELD-RT study. Results: Data extraction and manual review steps in the workflow represented significant time commitments for implementation of clinical ML on a prospective, randomized study. Barriers include limited data availability through the standard clinical workflow and commercial products, the need to aggregate data from multiple sources, and logistical challenges from altering the standard clinical workflow to deliver adaptive care. Conclusions: The SHIELD-RT study was an early randomized controlled study which enabled assessment of barriers to clinical ML implementation, specifically those which leverage the EHR. These challenges build on a growing body of literature and may provide lessons for future healthcare ML adoption. Trial registration: NCT04277650. Registered 20 February 2020. Retrospectively registered quality improvement study. [ABSTRACT FROM AUTHOR]

Sites 31CD967 and 31CD968 are situated in the North Carolina Sandhills on an upland setting overlooking an unnamed tributary of Rockfish Creek. Archaeological investigations produced multiple datasets including lithic and ceramic artifacts, organic absorbed residues, and thin-section ceramic samples. Analysis of these datasets revealed the sites were the product of short-term visits during the Middle Archaic and Early to Late Woodland periods. In addition, the ceramic analysis indicated a contention of assigning Hanover Fabric Impressed vessels into varieties I or II. [ABSTRACT FROM AUTHOR]

Lung cancer screening (LCS) is currently advocated in a subset of current or former smokers with a thirty pack-year smoking history or higher. Studies report that few patients meeting the criteria for screening are undergoing LCS. We conducted a survey to assess if barriers to LCS (race, ethnicity, and socioeconomic status) affect the perceptions about LCS that could influence screening uptake. We did not detect different perceptions based on race, ethnicity, or socioeconomic status; however, our survey found that fewer barriers and more benefits to LCS may be perceived in patients who undergo other types of health screening and more benefits for those with internet capable devices. [ABSTRACT FROM AUTHOR]

A solution exists: liver and pancreas tumor conspicuity can be substantially enhanced in CTsim data itself, utilizing diagnostic multiphasic contrast enhanced CT (MPCT) protocols. Unfortunately, many liver and pancreas tumors are nearly invisible in traditional contrastenhanced CT simulation (CTsim) scans. [Extracted from the article]

Purpose of Review: This review summarizes the relevant literature on the use of total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer. It highlights the most notable literature published and briefly discusses future directions.Recent Findings: Recent randomized trials evaluating TNT show improved rates of pathologic complete response and patient treatment tolerance with this approach.Summary: The rationale for TNT includes the poor patient tolerance of adjuvant chemotherapy and the persistent risk of distant disease in patients with locally advanced rectal cancer, despite improvements in local control. Randomized trials have focused on short-term pathologic endpoints. Ongoing phase 3 trials are evaluating long-term disease-related outcomes, allowing for a more thorough evaluation of this treatment paradigm. TNT may also facilitate organ preservation in appropriately selected patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is increasing in incidence and mortality. Although the prognosis remains poor, long-term survival has improved from 3% in 1970 to an 18% 5-year survival rate today. This is likely because of the introduction of well tolerated, oral antiviral therapies for hepatitis C. Curative options for patients with HCC are often limited by underlying liver dysfunction/cirrhosis and medical comorbidities. Less than one-third of patients are candidates for surgery, which is the current gold standard for cure. Nonsurgical treatments include embolotherapies, percutaneous ablation, and ablative radiation. Technological advances in radiation delivery in the past several decades now allow for safe and effective ablative doses to the liver. Conformal techniques allow for both dose escalation to target volumes and normal tissue sparing. Multiple retrospective and prospective studies have demonstrated that hypofractionated image-guided radiation therapy, used as monotherapy or in combination with other liver-directed therapies, can provide excellent local control that is cost effective. Therefore, as the HCC treatment paradigm continues to evolve, ablative radiation treatment has moved from a palliative treatment to both a "bridge to transplant" and a definitive treatment. [ABSTRACT FROM AUTHOR]

KRAS mutations drive resistance to targeted therapies, including EGFR inhibitors in colorectal cancer (CRC). Through genetic screens, we unexpectedly find that mutant HRAS, which is rarely found in CRC, is a stronger driver of resistance than mutant KRAS. This difference is ascribed to common codon bias in HRAS, which leads to much higher protein expression, and implies that the inherent poor expression of KRAS due to rare codons must be surmounted during drug resistance. In agreement, we demonstrate that primary resistance to cetuximab is dependent upon both KRAS mutational status and protein expression level, and acquired resistance is often associated with KRASQ61 mutations that function even when protein expression is low. Finally, cancer cells upregulate translation to facilitate KRASG12-driven acquired resistance, resulting in hypersensitivity to translational inhibitors. These findings demonstrate that codon bias plays a critical role in KRAS-driven resistance and provide a rationale for targeting translation to overcome resistance. [ABSTRACT FROM AUTHOR]

Wnt-1 inducible signalling pathway protein 1 (WISP-1/CCN4) is an extracellular matrix protein that belongs to the Cyr61 (cysteine-rich protein 61), CTGF (connective tissue growth factor) and NOV (CCN) family and plays a role in multiple cellular processes. No specific WISP-1 receptors have been identified but emerging evidence suggests WISP-1 mediates its downstream effects by binding to integrins. Here we describe a functional analysis of integrin receptor usage by WISP-1. Truncated WISP-1 proteins were produced using a baculovirus expression system. Full length WISP-1 and truncated proteins were evaluated for their ability to induce adhesion in A549 epithelial cells and β-catenin activation and CXCL3 secretion in fibroblasts (NRK49-F cells). Subsequent inhibition of these responses by neutralising integrin antibodies was evaluated. A549 cells demonstrated adhesion to full-length WISP-1 whilst truncated proteins containing VWC, TSP or CT domains also induced adhesion, with highest activity observed with proteins containing the C-terminal TSP and CT domains. Likewise the ability to induce β-catenin activation and CXCL3 secretion was retained in truncations containing C-terminal domains. Pre-treatment of A549s with either integrin αVβ5, αVβ3 or β1 neutralising antibodies partially inhibited full length WISP-1 induced adhesion whilst combining integrin αVβ5 and β1 antibodies increased the potency of this effect. Incubation of NRK49-F cells with integrin neutralising antibodies failed to effect β-catenin translocation or CXCL3 secretion. Analysis of natural WISP-1 derived from human lung tissue showed the native protein is a high order oligomer. Our data suggest that WISP-1 mediated adhesion of A549 cells is an integrin-driven event regulated by the C-terminal domains of the protein. Activation of β-catenin signalling and CXCL3 secretion also resides within the C-terminal domains of WISP-1 but are not regulated by integrins. The oligomeric nature of native WISP-1 may drive a high avidity interaction with these receptors in vivo. [ABSTRACT FROM AUTHOR]

Previous studies have shown associations between single nucleotide polymorphisms (SNPs) in gamma aminobutyric acid receptor alpha 2 ( GABRA2) and adolescent conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent alcohol dependence. The present study was intended as a replication and extension of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence (AAD), and adult AAD. Family based association tests were run using Hispanics and non-Hispanic European American subjects from two independent longitudinal samples. Although the analysis provided nominal support for an association with rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to replicate previous associations between two well replicated GABRA2 SNPs and CD and alcohol dependence. Overall, these results emphasize the utility of including an independent replication sample in the study design, so that the results from an individual sample can be weighted in the context of its reproducibility. [ABSTRACT FROM AUTHOR]

Introduction: Tobacco use is a complex behavior. The Old Order Amish community offers unique advantages for the study of tobacco use because of homogenous ancestral background, sociocultural similarity, sex-specific social norms regarding tobacco use, and large family size. Tobacco use in the Old Order Amish community is almost exclusively confined to males. Methods: We examined characteristics of tobacco use and familial aggregation among 1,216 Amish males from cross-sectional prospectively collected data. Outcomes examined included ever using tobacco regularly, current use, quantity of use, duration of use, and frequency of use. Results: Sixteen percent of Amish men were current tobacco users, with the majority reporting cigar use only. Higher rates of tobacco use were found among sons of fathers who smoked compared with sons of fathers who did not smoke (46% vs. 22%, p < .001) as well as among brothers of index cases who smoked compared with brothers of index cases who did not smoke (61% vs. 29%, p < .001). After controlling for shared household effects and age, heritability accounted for 66% of the variance in ever smoking regularly (p = .045). Conclusions: The familial patterns of tobacco use observed among Amish men highlight the important role of family in propagating tobacco use and support the usefulness of this population for future genetic studies of nicotine addiction. [ABSTRACT FROM PUBLISHER]

Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with new diagnostic targets and therapeutic strategies hold promise for more effective individualized anti-coagulation and anti-platelet therapy. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 18-year-old male who presented with 4 month history of frontal headaches and rhinorrhea; he had a 1 year history of chronic sinusitis.Physical examination and blood test were conducted; a CT scan showed a left frontal epidural abscess and blood cultures revaled presenece of Fusobacterium necrophorum which causes epidural abscess and orbital cellulitis secondary to chronic sinusitis. He was administered metronidazole and meropenem and recovered completely.

The article discusses a study on the effect of the interaction between age at onset and rs16969968 on the risk of heavy smoking. Sex, birth cohort and educational attainment were evaluated in addition to age at onset and rs16969968. The study is the first large-scale systematic investigation of variation in the association between rs16969968 and CPD across strata of age at onset of smoking. It suggests increased association between cigarettes per day (CPD) and rs16969968 in early onset smokers.

Multiple studies have provided evidence for genetic associations between single nucleotide polymorphisms (SNPs) located on the CHRNA5/ A3/ B4 gene cluster and various phenotypes related to Nicotine Dependence (Greenbaum et al. ). Only a few studies have investigated other substances of abuse. The current study has two aims, (1) to extend previous findings by focusing on associations between the CHRNA5/ A3/ B4 gene cluster and age of initiation of several different substances, and (2) to investigate heterogeneity in age of initiation across the different substances. All analyses were conducted with a subset of the Add Health study with available genetic data. The first aim was met by modeling onset of tobacco, alcohol, cannabis, inhalants, and other substance use using survival mixture analysis (SMA). Ten SNPs in CHRNA5/ A3/ B4 were used to predict phenotypic differences in the risk of onset, and differences between users and non-users. The survival models aim at investigating differences in the risk of initiation across the 5-18 age range for each phenotype separately. Significant or marginally significant genetic effects were found for all phenotypes. The genetic effects were mainly related to the risk of initiation and to a lesser extent to discriminating between users and non-users. To address the second goal, the survival analyses were complemented by a latent class analysis that modeled all phenotypes jointly. One of the ten SNPs was found to predict differences between the early and late onset classes. Taken together, our study provides evidence for a general role of the CHRNA5/ A3/ B4 gene cluster in substance use initiation that is not limited to nicotine and alcohol. [ABSTRACT FROM AUTHOR]

There is strong evidence for shared genetic factors contributing to childhood externalizing disorders and substance abuse. Externalizing disorders often precede early substance experimentation, leading to the idea that individuals inherit a genetic vulnerability to generalized disinhibitory psychopathology. Genetic variation in the CHRNA5/ CHRNA3/ CHRNB4 gene cluster has been associated with early substance experimentation, nicotine dependence, and other drug behaviors. This study examines whether the CHRNA5/ CHRNA3/ CHRNB4 locus is correlated also with externalizing behaviors in three independent longitudinally assessed adolescent samples. We developed a common externalizing behavior phenotype from the available measures in the three samples, and tested for association with 10 SNPs in the gene cluster. Significant results were detected in two of the samples, including rs8040868, which remained significant after controlling for smoking quantity. These results expand on previous work focused mainly on drug behaviors, and support the hypothesis that variation in the CHRNA5/ CHRNA3/ CHRNB4 locus is associated with early externalizing behaviors. [ABSTRACT FROM AUTHOR]

Ultrasound was used for sex identification and female maturity assessment of Pacific halibutHippoglossus stenolepisranging from 64- to 144-cm fork length collected during their nonspawning period (boreal summer) in the central and eastern Gulf of Alaska. Ultrasonic sex identification employed inspection of gross morphology and gonadal morphometrics, the latter involving determination of gonad length (maximum posterior gonad extent [MPGE]) and testing for difference between sexes. Morphometric analysis was refined further for females by removing ovaries, macroscopically determining maturity status, and comparing MPGE and proportional ovarian length (POL) among maturity stages. Ultrasonically determined gross morphology was sufficient to achieve accurate sex identification in even the smallest individuals examined. Ovaries were rounded anteriorly with no apparent internal structure, whereas testes were sickle-shaped with characteristic internal structure formed by the junctures between testicular lobes. Maximum posterior gonad extent was significantly greater for females but did not provide accurate sex determination because values overlapped considerably between sexes; 80% of all fish (n= 147) exhibited MPGE within the range of overlap. Values of both MPGE and POL overlapped considerably between mature and immature females, but threshold values were identified for both metrics above which all individuals were mature. Only for POL was a lower threshold apparent, below which all individuals were immature. Considering MPGE and POL simultaneously suggested a possible means for identifying first-time spawners and may warrant additional investigation. Received January 13, 2011; accepted June 2, 2011 [ABSTRACT FROM PUBLISHER]

Evolutionary genetic models predict that the cumulative effect of rare deleterious mutations across the genome-known as mutational load burden-increases the susceptibility to complex disease. To test the mutational load burden hypothesis, we adopted a two-tiered approach: assessing the impact of whole-exome minor allele load burden and then conducting individual-gene screening. For our primary analysis, we examined various minor allele frequency (MAF) thresholds and weighting schemes to examine the overall effect of minor allele load on affection status. We found a consistent association between minor allele load and affection status, but this effect did not markedly increase within rare and/or functional single-nucleotide polymorphisms (SNPs). Our follow-up analysis considered minor allele load in individual genes to see whether only one or a few genes were driving the overall effect. Examining our most significant result-minor allele load of nonsynonymous SNPs with MAF < 2.4%-we detected no significantly associated genes after Bonferroni correction for multiple testing. After moderately significant genes (p < 0.05) were removed, the overall effect of rare nonsynonymous allele load remained significant. Overall, we did not find clear support for mutational load burden on affection status; however, these results are ultimately dependent on and limited by the nature of the Genetic Analysis Workshop 17 simulation. [ABSTRACT FROM AUTHOR]

The article discusses gender discrimination in Australia despite a renewed focus to eliminate it and mentions Section 7D of the Commonwealth Sex Discrimination Act 1984, which permits the taking of special measures for the purpose of achieving substantive equality between men and women.

B INTRODUCTION: b Acute ANCA vasculitis with in-hospital development of alveolar hemorrhage results in significant mortality of up to 24%. Furthermore, ANCA-associated vasculitis has a 90% 2-year mortality if left untreated, which significantly decreases to 74% 5-year mortality in patients receiving prompt corticosteroid therapy. It is important to promptly recognize and treat late onset ANCA vasculitis, especially in patients requiring critical care admission. [Extracted from the article]

Presents an abstract for the article on the optimization of a dedicated DNA microarray system for high-throughput gene expression analysis.