Military Sexual Trauma Among Recent Veterans: Correlates of Sexual Assault and Sexual Harassment.

INTRODUCTION: Military sexual trauma (MST) includes sexual harassment or sexual assault that occurs during military service and is of increasing public health concern. The population prevalence of MST among female and male veterans who served during Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) has not been estimated to our knowledge. The purpose of this study is to assess the population prevalence and identify military correlates of MST, sexual harassment, and sexual assault among OEF/OIF veterans. METHODS: MST was assessed in the 2009-2011 National Health Study for a New Generation of U.S. Veterans, a survey of 60,000 veterans who served during the OEF/OIF eras (response rate, 34%, n=20,563). Weighted prevalence estimates and AORs of MST, sexual harassment, and sexual assault among women and men were calculated. Gender-stratified logistic regression models controlled for military and demographic characteristics. Data analyses were conducted in 2013-2014. RESULTS: Approximately 41% of women and 4% of men reported experiencing MST. Deployed men had lower risk for MST compared with non-deployed men, though no difference was found among women. However, veterans reporting combat exposure during deployment had increased risk for MST compared with those without, while controlling for OEF/OIF deployment. Among women, Marines and Navy veterans had increased risk for MST compared with Air Force veterans. MST was significantly higher among veterans who reported using Veterans Affairs healthcare services. CONCLUSIONS: These prevalence estimates underscore the importance of public awareness and continued investigation of the public health impact of MST.

Evaluation of Liver Fibrosis Using Texture Analysis on Combined-Contrast-Enhanced Magnetic Resonance Images at 3.0T.

PURPOSE: To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE) magnetic resonance imaging (MRI) and texture analysis. MATERIALS AND METHODS: In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained area). Using L 1 regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC) and correlation analyses. RESULTS: The texture-based predicted fibrosis score significantly correlated with qualitative (r = 0.698, P < 0.001) and quantitative (r = 0.757, P < 0.001) histology. The prediction model for qualitative histology had 0.814-0.976 areas under the curve (AUC), 0.659-1.000 sensitivity, 0.778-0.930 specificity, and 0.674-0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742-0.950 AUC, 0.688-1.000 sensitivity, 0.679-0.857 specificity, and 0.696-0.848 accuracy, depending on the binary classification threshold. CONCLUSION: CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.

Health care utilization behavior of veterans who deployed to Afghanistan and Iraq.

BACKGROUND: Previous assessments of Afghanistan/Iraq Veterans have lacked a systematic overview of all injury and illness experiences captured by the Veterans Health Administration (VHA) health care services. In this initial study, we quantify the health care utilization behavior of eligible Veterans and describe the level and type of usage among them. METHODS: A roster of service members who have served in Afghanistan/Iraq and became eligible for VHA care between 2002 and 2010 and their corresponding administrative VA medical encounter data were abstracted from the VHA Office of Public Health Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Health Surveillance System. RESULTS: Between 2002 and 2010, approximately 55% of eligible Veterans accessed VHA health care. Higher utilization was observed among Veterans 50 years of age and older compared to younger Veterans. Higher utilization was also observed among Veterans with increasing cumulative deployment time. Mental disorder diagnostic codes accounted for the greatest number of visits per Veteran. CONCLUSIONS: Veterans with mental health diagnoses may need a different level of care than other VHA users. Other service factors associated with utilization require further research to better understand the underlying relationship. Current observed results may be reflective of future expected utilization patterns and may assist in resource planning and research.

Diagnostic Accuracy of Preoperative Gadoxetic Acid-enhanced 3-T MR Imaging for Malignant Liver Lesions by Using Ex Vivo MR Imaging-matched Pathologic Findings as the Reference Standard.

PURPOSE: To determine per-lesion sensitivity and positive predictive value (PPV) of gadoxetic acid-enhanced 3-T magnetic resonance (MR) imaging for the diagnosis of malignant lesions by using matched (spatially correlated) hepatectomy pathologic findings as the reference standard. Materials and METHODS: In this prospective, institutional review board-approved, HIPAA-compliant study, 20 patients (nine men, 11 women; mean age, 59 years) with malignant liver lesions who gave written informed consent underwent preoperative gadoxetic acid-enhanced 3-T MR imaging for surgical planning. Two image sets were independently analyzed by three readers to detect liver lesions (set 1 without and set 2 with hepatobiliary phase [HBP] images). Hepatectomy specimen ex vivo MR imaging assisted in matching gadoxetic acid-enhanced 3-T MR imaging findings with pathologic findings. Interreader agreement was assessed by using the Cohen κ coefficient. Per-lesion sensitivity and PPV were calculated. RESULTS: Cohen κ values were 0.64-0.76 and 0.57-0.84, and overall per-lesion sensitivity was 45% (42 of 94 lesions) to 56% (53 of 94 lesions) and 58% (55 of 94 lesions) to 64% (60 of 94 lesions) for sets 1 and 2, respectively. The addition of HBP imaging did not affect interreader agreement but significantly improved overall sensitivity for one reader (P < .05) and almost for another (P = .05). Sensitivity for 0.2-0.5-cm lesions was 0% (0 of 26 lesions) to 8% (two of 26 lesions) for set 1 and 4% (one of 26 lesions) to 12% (three of 26 lesions) for set 2. Sensitivity for 0.6-1.0-cm lesions was 28% (nine of 32 lesions) to 59% (19 of 32 lesions) for set 1 and 66% (21 of 32 lesions) to 69% (22 of 32 lesions) for set 2. Sensitivity for lesions at least 1.0 cm in diameter was at least 81% (13 of 16 lesions) for set 1 and was not improved for set 2. PPV was 98% (56 of 57 lesions) to 100% (60 of 60 lesions) for all readers without differences between image sets or lesion size. CONCLUSION: Gadoxetic acid-enhanced 3-T MR imaging provides high per-lesion sensitivity and PPV for preoperative malignant liver lesion detection overall, although sensitivity for 0.2-0.5-cm malignant lesions is poor.

Immunodeficiency and autoimmune enterocolopathy linked to NFAT5 haploinsufficiency.

The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.

Features: Health Care Use Among Iraq and Afghanistan Veterans With Infectious Diseases.

Qualified veterans were no more likely to take advantage of health care services after the VA presumptive infectious disease determination streamlined the qualification process.

Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Little is known about how weight loss affects magnetic resonance imaging (MRI) of liver fat and volume or liver histology in patients with nonalcoholic steatohepatitis (NASH). We measured changes in liver fat and liver volume associated with weight loss by using an advanced MRI method. METHODS: We analyzed data collected from a previous randomized controlled trial in which 43 adult patients with biopsy-proven NASH underwent clinical evaluation, biochemical tests, and MRI and liver biopsy analyses at the start of the study and after 24 weeks. We compared data between patients who did and did not have at least 5% decrease in body mass index (BMI) during the study period. RESULTS: Ten of 43 patients had at least a 5% decrease in BMI during the study period. These patients had a significant decrease in liver fat, which was based on MRI proton density fat fraction estimates (18.3% ± 7.6% to 13.6% ± 13.6%, P = .03), a relative 25.5% reduction. They also had a significant decrease in liver volume (5.3%). However, no significant changes in levels of alanine aminotransferase or aspartate aminotransferase were observed with weight loss. Thirty-three patients without at least 5% decrease in BMI had insignificant increases in estimated liver fat fraction and liver volume. CONCLUSIONS: A reduction in BMI of at least 5% is associated with significant decrease in liver fat and volume in patients with biopsy-proven NASH. These data should be considered in assessing effect size in studies of patients with nonalcoholic fatty liver disease or obesity that use MRI-estimated liver fat and volume as end points.

Effects of Landau level mixing on the fractional quantum Hall effect in monolayer graphene.

We report results of exact diagonalization studies of the spin- and valley-polarized fractional quantum Hall effect in the N = 0 and N = 1 Landau levels in graphene. We use an effective model that incorporates Landau level mixing to lowest order in the parameter κ = ((e(2)/εℓ)/(hv(F)/ℓ)) = (e(2)/εv(F)h), which is magnetic field independent and can only be varied through the choice of substrate. We find Landau level mixing effects are negligible in the N = 0 Landau level for κ ≲ 2. In fact, the lowest Landau level projected Coulomb Hamiltonian is a better approximation to the real Hamiltonian for graphene than it is for semiconductor based quantum wells. Consequently, the principal fractional quantum Hall states are expected in the N = 0 Landau level over this range of κ. In the N = 1 Landau level, fractional quantum Hall states are expected for a smaller range of κ and Landau level mixing strongly breaks particle-hole symmetry, producing qualitatively different results compared to the N = 0 Landau level. At half filling of the N = 1 Landau level, we predict the anti-Pfaffian state will occur for κ ∼ 0.25-0.75.

Genome-wide mutational landscape of mucinous carcinomatosis peritonei of appendiceal origin.

BACKGROUND: Mucinous neoplasms of the appendix (MNA) are rare tumors which may progress from benign to malignant disease with an aggressive biological behavior. MNA is often diagnosed after metastasis to the peritoneal surfaces resulting in mucinous carcinomatosis peritonei (MCP). Genetic alterations in MNA are poorly characterized due to its low incidence, the hypo-cellularity of MCPs, and a lack of relevant pre-clinical models. As such, application of targeted therapies to this disease is limited to those developed for colorectal cancer and not based on molecular rationale. METHODS: We sequenced the whole exomes of 10 MCPs of appendiceal origin to identify genome-wide somatic mutations and copy number aberrations and validated significant findings in 19 additional cases. RESULTS: Our study demonstrates that MNA has a different molecular makeup than colorectal cancer. Most tumors have co-existing oncogenic mutations in KRAS (26/29) and GNAS (20/29) and are characterized by downstream PKA activation. High-grade tumors are GNAS wild-type (5/6), suggesting they do not progress from low-grade tumors. MNAs do share some genetic alterations with colorectal cancer including gain of 1q (5/10), Wnt, and TGFß pathway alterations. In contrast, mutations in TP53 (1/10) and APC (0/10), common in colorectal cancer, are rare in MNA. Concurrent activation of the KRAS and GNAS mediated signaling pathways appears to be shared with pancreatic intraductal papillary mucinous neoplasm. CONCLUSIONS: MNA genome-wide mutational analysis reveals genetic alterations distinct from colorectal cancer, in support of its unique pathophysiology and suggests new targeted therapeutic opportunities.

Prevalence of respiratory diseases among veterans of Operation Enduring Freedom and Operation Iraqi Freedom: results from the National Health Study for a New Generation of U.S. Veterans.

This study investigated the population prevalence of asthma, bronchitis, and sinusitis among veterans deployed to Afghanistan and Iraq compared to nondeployed veterans. A 2009-2011 population-based health survey of 60,000 veterans (34% response rate) asked about the history of doctor-diagnosed respiratory disease. Analyses included smoking history, deployment status, and year of diagnosis. The prevalence of asthma, bronchitis, and sinusitis among those diagnosed during or after 2001 was 3.3%, 5.9%, and 6.9%, respectively, among the deployed veterans and 3.4%, 5.3%, and 5.6%, respectively, among the nondeployed veterans. Deployed veterans were 29% more likely to have been diagnosed with sinusitis during and after 2001 compared to nondeployed veterans (adjusted odds ratio = 1.30, 95% confidence interval = 1.13, 1.49). Deployed veterans are at increased risk for sinusitis compared to nondeployed. There was no significant difference in asthma or bronchitis risk between deployed and nondeployed veterans.

Malignant cell contamination may lead to false-positive findings at endosonographic fine needle aspiration for tumor staging.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of lymph nodes is used for staging of gastrointestinal malignancies. False-positive rates of 5 % - 7 % are not well understood. Elements of EUS examinations that contribute to false-positive cytological findings were investigated. PATIENTS AND METHODS: 13 patients undergoing EUS staging of gastrointestinal luminal malignancy were consecutively enrolled together with 3 patients with extraluminal tumors (pancreas, lung) defined as controls. After EUS, cellular debris and fluid were collected from the FNA needle catheter, instrument channel, and endoscope tip for cytologic and histologic investigation. RESULTS: 6 of 13 patients (46 %) had malignant cells contaminating the FNA needle catheter, instrument channel, or endoscope tip. Malignant cells were present in the instrument channel in 5 cases (38 %), exterior tip of echoendoscope in 4 (31 %) and needle catheter in 2 (15 %). CONCLUSIONS: Echoendoscopes used for FNA in patients with luminal tumors are at risk for malignant cell contamination of the instrument channel, FNA needle catheter, and echoendoscope tip. FNA needle contamination can contribute to false-positive findings.

Insulin Resistance Increases MRI-Estimated Pancreatic Fat in Nonalcoholic Fatty Liver Disease and Normal Controls.

Background. Ectopic fat deposition in the pancreas and its relationship with hepatic steatosis and insulin resistance have not been compared between patients with nonalcoholic fatty liver disease (NAFLD) and healthy controls. Aim. Using a novel magnetic resonance imaging (MRI) based biomarker, the proton-density-fat-fraction (MRI-PDFF), we compared pancreatic fat content in patients with biopsy-proven NAFLD to healthy controls and determined whether it is associated with insulin resistance and liver fat content. Methods. This nested case-control study was derived from two prospective studies including 43 patients with biopsy-proven NAFLD and 49 healthy controls who underwent biochemical testing and MRI. Results. Compared to healthy controls, patients with NAFLD had significantly higher pancreatic MRI-PDFF (3.6% versus 8.5%, P value <0.001), and these results remained consistent in multivariable-adjusted models including age, sex, body mass index, and diabetes (P value =0.03). We found a strong correlation between hepatic and pancreatic MRI-PDFF (Spearman correlation, P = 0.57, P value <0.001). Participants with increased insulin resistance determined by homeostatic-model-of-insulin-resistance (HOMA-IR) greater than 2.5 had higher pancreatic (7.3% versus 4.5%, P value =0.015) and liver (13.5% versus 4.0%, P value <0.001) MRI-PDFF. Conclusion. Patients with NAFLD have greater pancreatic fat than normal controls. Insulin resistance is associated with liver and pancreatic fat accumulation.

Analysis of the effect of various decalcification agents on the quantity and quality of nucleic acid (DNA and RNA) recovered from bone biopsies.

Molecular studies are part of standard care for cancer patients. Bone, a common and sometimes sole site of metastasis, requires decalcification for morphological examination. Many commonly used decalcification agents contain strong acids that degrade nucleic acids. The paradigm shift in oncology, with biomarker targeted therapy and gene expression profiling analysis, requires sufficient nucleic acid recovery from bone biopsy specimens. We systematically studied the effects of a spectrum of decalcification agents on the quantity and quality of RNA and DNA recovered from bone biopsies. Multiple bone biopsies of similar size and cellularity were fixed in 10% neutral-buffered formalin, randomized to various decalcification agents for 2 hours then processed, and embedded. Tissue lysates were obtained from unstained sections and nucleic acid isolated. DNA and RNA were quantified. Assessment of DNA and RNA integrity was accomplished by comparison of the average cycle threshold by polymerase chain reaction of selected housekeeping genes for each agent. Results were then analyzed by 2-sample t test. There was a significant decrease in both DNA and RNA yield and integrity with strong acids (hydrochloric, nitric) vs 14% EDTA and formic acid. DNA yield was (mean nanograms) 6.15 vs 68.68 (P<.001) and RNA was (mean nanograms) 121.53 vs 288.89 (P=.003), respectively. DNA integrity (mean cycle threshold) was 35.79 vs 30.16 (P<.001), and RNA was 33.03 vs 26.5 (P<.001), respectively. Decalcification of bone biopsies with EDTA or formic acid agents was associated with a significant improvement in recovered nucleic acid quantity and quality.

Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials.

UNLABELLED: The magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) is a novel imaging-based biomarker that allows fat mapping of the entire liver, whereas the magnetic resonance spectroscopy-measured proton density fat fraction (MRS-PDFF) provides a biochemical measure of liver fat in small regions of interest. Cross-sectional studies have shown that MRI-PDFF correlates with MRS-PDFF. The aim of this study was to show the utility of MRI-PDFF in assessing quantitative changes in liver fat through a three-way comparison of MRI-PDFF and MRS-PDFF with the liver histology-determined steatosis grade at two time points in patients with nonalcoholic fatty liver disease (NAFLD). Fifty patients with biopsy-proven NAFLD who participated in a randomized trial underwent a paired evaluation with liver biopsy, MRI-PDFF, and MRS-PDFF at the baseline and 24 weeks. The mean age and body mass index were 47.8 ± 11.7 years and 30.7 ± 6.5 kg/m(2), respectively. MRI-PDFF showed a robust correlation with MRS-PDFF both at week 0 and at week 24 (r = 0.98, P < 0.0001 for both). Cross-sectionally, MRI-PDFF and MRS-PDFF increased with increases in the histology-determined steatosis grade both at week 0 and at week 24 (P < 0.05 for all). Longitudinally, patients who had a decrease (≥ 1%) or increase (≥ 1%) in MRI-PDFF (confirmed by MRS-PDFF) showed a parallel decrease or increase in their body weight and serum alanine aminotransferase and aspartate aminotransferase levels at week 24 (P < 0.05). This small increase or decrease in liver fat could not be quantified with histology. CONCLUSION: In this longitudinal study, MRI-PDFF correlated well with MRS-PDFF and was more sensitive than the histology-determined steatosis grade in quantifying increases or decreases in the liver fat content. Therefore, it could be used to quantify changes in liver fat in future clinical trials.

Examination of sources of diagnostic error leading to cervical cone biopsies with no evidence of dysplasia.

At our institution, 17% of cervical conization specimens are reported as negative for dysplasia or malignancy. To identify sources of error, we reviewed 53 negative conization specimens and their prior and follow-up cytology, biopsy, and endocervical curettage specimens. Examination of deeper-level sections and p16 immunostaining were performed on all conization specimens and selected biopsy specimens. Dysplasia was detected in 26% (14/53) of conization specimens. Twenty-eight percent (15/53) of cones were truly negative, and the presurgical material had been overcalled as high-grade squamous intraepithelial lesions (HSIL). Forty-five percent (24/53) of cones were truly negative and HSIL was confirmed in the presurgical material. Of these, 11% (6/53) showed subsequent evidence of residual dysplasia and 26% (14/53) were negative on further follow-up. Deeper-level sections, p16 immunostains, and consensus review may help identify squamous dysplasia in conization specimens and may prevent the overdiagnosis of HSIL on cervical biopsies.

TAMIS-assisted laparoscopic low anterior resection with total mesorectal excision in a cadaveric series.

BACKGROUND: To demonstrate the feasibility of an innovative technique for the surgical management of rectal cancer, we performed transanal minimally invasive surgery assisted low anterior resection with total mesorectal excision (TAMIS-assisted LAR with TME) in a cadaver model. Transanal LAR via natural orifice transluminal endoscopic surgery has been reported in cadaveric series using rigid transanal platforms. This procedure has not been described using a combination of a single incision laparoscopy and TAMIS transanal endoscopic platform. We describe the first cadaveric series of TAMIS-assisted LAR with TME. METHODS: TAMIS-assisted LAR with TME was successfully performed in five fresh human cadavers. The procedure was performed using the mini-Gelpoint single incision platform and the Gelpoint Path TAMIS platform (Applied Medical, Rancho Santa Margarita, CA). The variables recorded were age, body mass index (BMI), operative time, complications, and specimen length. The grade of the TME was determined by evaluation of the specimen by photo documentation by a gastrointestinal pathologist. RESULTS: All cadavers were male with a mean age of 71 ± 8 years and mean BMI of 28 ± 3 kg/m(2). The mean operative time was 200 ± 55 min (range 128-249 min). The quality of the TME was grade I (complete) with intact mesorectum in all five cases. The mean specimen length was 36.8 ± 3.4 cm. CONCLUSIONS: TAMIS-assisted LAR with TME was feasible. A high-quality TME can be achieved using this innovative technique. Transanal endoscopic total mesorectal dissection may revolutionize the surgical management of rectal cancer. However, multicenter clinical trials are needed to further evaluate the oncologic safety and surgical outcomes of transanal endoscopic TME using various platforms before widespread application of this new technique.

Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: a randomized controlled trial.

UNLABELLED: Bile acid sequestrants (BAS) lower plasma low density lipoprotein levels and improve glycemic control. Colestimide, a BAS, has been claimed by computed tomography to reduce liver fat. Therefore, we examined the efficacy of colesevelam, a potent BAS, to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liver fat was measured by a novel magnetic resonance imaging (MRI) technique, the proton-density-fat-fraction (PDFF), as well as by conventional MR spectroscopy (MRS). Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 g/day orally or placebo for 24 weeks. The primary outcome was change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Compared with placebo, colesevelam increased liver fat by MRI-PDFF in all nine segments of the liver with a mean difference of 5.6% (P = 0.002). We cross-validated the MRI-PDFF-determined fat content with that assessed by colocalized MRS; the latter showed a mean difference of 4.9% (P = 0.014) in liver fat between the colesevelam and the placebo arms. MRI-PDFF correlated strongly with MRS-determined hepatic fat content (r(2) = 0.96, P < 0.0001). Liver biopsy assessment of steatosis, cellular injury, and lobular inflammation did not detect any effect of treatment. CONCLUSION: Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR-detected increase in liver fat has clinical consequences is not known.

Schistosomiasis and signet ring cell carcinoma of the rectum.

A definitive link between Schistosoma hematobium infection and squamous cell carcinoma of the bladder has been identified. A weaker association between S japonicum infection and colorectal neoplasia has been proposed, although reports are limited to case reports, a case series, and epidemiologic studies. Virtually all cases presented in the literature describe intestinal-type adenocarcinoma occurring in association with S japonicum. We here describe a 40-year-old male Filipino patient with signet ring cell carcinoma of the rectum and evidence of infection by S japonicum.