Chronic Rejection and Extrahepatic Biliary Tract Obstruction 8 Years After Orthotopic Liver Transplantation Using the Gallbladder-Conduit Technique

A case of delayed biliary obstruction and cholangitis, occurring in the setting of chronic allograft rejection, 8 years after liver transplantation using the gallbladder-conduit, is presented. Extrahepatic biliary obstruction may be seen in the late follow-up of liver grafting and rejection phenomena may play a significant role in the development of such obstruction

Fracture Propagation Driven by Fluid Outflow from a Low-permeability Aquifer

Deep saline aquifers are promising geological reservoirs for CO2 sequestration if they do not leak. The absence of leakage is provided by the caprock integrity. However, CO2 injection operations may change the geomechanical stresses and cause fracturing of the caprock. We present a model for the propagation of a fracture in the caprock driven by the outflow of fluid from a low-permeability aquifer. We show that to describe the fracture propagation, it is necessary to solve the pressure diffusion problem in the aquifer. We solve the problem numerically for the two-dimensional domain and show that, after a relatively short time, the solution is close to that of one-dimensional problem, which can be solved analytically. We use the relations derived in the hydraulic fracture literature to relate the the width of the fracture to its length and the flux into it, which allows us to obtain an analytical expression for the fracture length as a function of time. Using these results we predict the propagation of a hypothetical fracture at the In Salah CO2 injection site to be as fast as a typical hydraulic fracture. We also show that the hydrostatic and geostatic effects cause the increase of the driving force for the fracture propagation and, therefore, our solution serves as an estimate from below. Numerical estimates show that if a fracture appears, it is likely that it will become a pathway for CO2 leakage.Comment: 21 page

A pharmacogenetic risk score for the evaluation of major depression severity under treatment with antidepressants

The severity of symptoms as well as efficacy of antidepressants in major depressive disorder (MDD) is modified by single nucleotide polymorphisms (SNPs) in different genes, which may contribute in an additive or synergistic fashion. We aimed to investigate depression severity in participants with MDD under treatment with antidepressants in relation to the combinatory effect of selected genetic variants combined using a genetic risk score (GRS). The sample included 150 MDD patients on regular AD therapy from the population-based Swiss PsyCoLaus cohort. We investigated 44 SNPs previously associated with antidepressant response by ranking them with regard to their association to the Center for Epidemiologic Studies Short Depression Scale (CES-D) score using random forest. The three top scoring SNPs (rs12248560, rs878567, rs17710780) were subsequently combined into an unweighted GRS, which was included in linear and logistic regression models using the CES-D score, occurrence of a major depressive episode (MDE) during follow-up and regular antidepressant treatment during the 6 months preceding follow-up assessment as outcomes. The GRS was associated with MDE occurrence (p =.02) and ln CES-D score (p =.001). The HTR1A rs878567 variant was associated with ln CES-D after adjustment for demographic and clinical variables [p =.02, lower scores for minor allele (G) carriers]. Additionally, rs12248560 (CYP2C19) CC homozygotes showed a six-fold higher likelihood of regular AD therapy at follow-up compared to minor allele homozygotes [TT; ultrarapid metabolizers (p =.03)]. Our study suggests that the cumulative consideration of pharmacogenetic risk variants more reliably reflects the impact of the genetic background on depression severity than individual SNPs

Prevalence and predictors of psychological distress before, during, and after a COVID-19 pandemic wave in Switzerland, 2021.

There are concerns about acute and long-term mental health effects of the COVID-19 pandemic. This study examined the prevalence and predictors of psychological distress before, during, and after a pandemic wave in Switzerland, 2021. Prevalence of psychological distress was estimated in adults aged 35-96 years using the General Health Questionnaire-12 administered in June 2021 (Specchio-COVID19 cohort, N = 3965), and compared to values from 2003 to 2006 (CoLaus|PsyCoLaus cohort, N = 5667). Anxiety and depression were assessed from February to June 2021 using the Generalised Anxiety Disorder scale-2 and the Patient Health Questionnaire-2, respectively. Prevalence of psychological distress in June 2021, after the pandemic wave (16.0% [95% CI, 14.6%-17.4%]) was comparable to pre-pandemic levels (15.1% [14.0%-16.2%]). Anxiety and depression were highest at the start of the pandemic wave in February 2021, and declined from February to June with the relaxation of measures. Predictors of psychological distress included being younger, female, a single parent, unemployed, a change in working hours or job loss in the past 6 months, greater perceived severity and contagiousness of COVID-19, and self-reported post COVID-19. By June 2021, following a pandemic wave, prevalence of psychological distress in Switzerland was closer to pre-pandemic levels. These findings highlight the need for additional mental health support during times of stricter government policies relating to COVID-19; yet they also suggest that individuals can adapt relatively quickly to the changing context

Bi-directional association between depression and HF: An electronic health records-based cohort study.

To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs). This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 1:1 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions. 2,024 occurrences of newly diagnosed HF were observed in the depression cohort and 944 occurrences of newly diagnosed depression were observed in the HF cohort over approximately 4-6 years of follow-up. People with depression had significantly increased risk for developing newly diagnosed HF (HR 2.08, 95% CI 1.89-2.28) and people with HF had a significantly increased risk of newly diagnosed depression (HR 1.34, 95% CI 1.17-1.54) after adjusting for all 16 comorbid chronic conditions. These results provide evidence of a bi-directional relationship between depression and HF independently of age, sex, and multimorbidity from chronic illnesses

Prevalence and determinants of periodic limb movements in the general population.

OBJECTIVE: Periodic limb movements during sleep (PLMS) are sleep phenomena characterized by periodic episodes of repetitive stereotyped limb movements. The aim of this study was to describe the prevalence and determinants of PLMS in a middle to older aged general population. METHODS: Data from 2,162 subjects (51.2% women, mean age = 58.4 ± 11.1 years) participating in a population-based study (HypnoLaus, Lausanne, Switzerland) were collected. Assessments included laboratory tests, sociodemographic data, personal and treatment history, and full polysomnography at home. PLMS index (PLMSI) was determined, and PLMSI > 15/h was considered as significant. RESULTS: Prevalence of PLMSI > 15/h was 28.6% (31.3% in men, 26% in women). Compared to subjects with PLMSI ≤ 15/h, subjects with PLMSI > 15/h were older (p < 0.001), were predominantly males (p = 0.007), had a higher proportion of restless legs syndrome (RLS; p < 0.001), had a higher body mass index (p = 0.001), and had a lower mean glomerular filtration rate (p < 0.001). Subjects with PLMSI > 15/h also had a higher prevalence of diabetes, hypertension, and beta-blocker or hypnotic treatments. The prevalence of antidepressant use was higher, but not statistically significant (p = 0.07). Single nucleotide polymorphisms (SNPs) within BTBD9 (rs3923809), TOX3 (rs3104788), and MEIS1 (rs2300478) genes were significantly associated with PLSMI > 15/h. Conversely, mean hemoglobin and ferritin levels were similar in both groups. In the multivariate analysis, age, male gender, antidepressant intake, RLS, and rs3923809, rs3104788, and rs2300478 SNPs were independently associated with PLMSI > 15/h. INTERPRETATION: PLMS are highly prevalent in our middle-aged European population. Age, male gender, RLS, antidepressant treatment, and specific BTBD9, TOX3, and MEIS1 SNP distribution are independent predictors of PLMSI > 15/h. ANN NEUROL 2016;79:464-474

REM-associated sleep apnoea: prevalence and clinical significance in the HypnoLaus cohort

This study determined the prevalence of rapid eye movement (REM) related sleep-disordered breathing (REM-SDB) in the general population and investigated the associations of REM-SDB with hypertension, metabolic syndrome, diabetes and depression.Home polysomnography (PSG) recordings (n=2074) from the population-based HypnoLaus Sleep Cohort (48.3% men, 57±11 years old) were analysed. The apnoea-hypopnoea index was measured during REM and non-REM sleep (as REM-AHI and NREM-AHI, respectively). Regression models were used to explore the associations between REM-SDB and hypertension, diabetes, metabolic syndrome and depression in the entire cohort and in subgroups with NREM-AHI <10 events·h <sup>-1</sup> and total AHI <10 events·h <sup>-1</sup> The prevalence of REM-AHI ≥20 events·h <sup>-1</sup> was 40.8% in the entire cohort. An association between increasing REM-AHI and metabolic syndrome was found in the entire cohort and in both the NREM-AHI and AHI subgroups (p-trend=0.014, <0.0001 and 0.015, respectively). An association was also found between REM-AHI ≥20 events·h <sup>-1</sup> and diabetes in both the NREM-AHI <10 events·h <sup>-1</sup> (odds ratio (OR) 3.12 (95% CI 1.35-7.20)) and AHI <10 events·h <sup>-1</sup> (OR 2.92 (95% CI 1.12-7.63)) subgroups. Systolic and diastolic blood pressure were positively associated with REM-AHI ≥20 events·h <sup>-1</sup> REM-SDB is highly prevalent in our middle-to-older age sample and is independently associated with metabolic syndrome and diabetes. These findings suggest that an increase in REM-AHI could be clinically relevant

Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study.

BACKGROUND: Sleep-disordered breathing is associated with major morbidity and mortality. However, its prevalence has mainly been selectively studied in populations at risk for sleep-disordered breathing or cardiovascular diseases. Taking into account improvements in recording techniques and new criteria used to define respiratory events, we aimed to assess the prevalence of sleep-disordered breathing and associated clinical features in a large population-based sample. METHODS: Between Sept 1, 2009, and June 30, 2013, we did a population-based study (HypnoLaus) in Lausanne, Switzerland. We invited a cohort of 3043 consecutive participants of the CoLaus/PsyCoLaus study to take part. Polysomnography data from 2121 people were included in the final analysis. 1024 (48%) participants were men, with a median age of 57 years (IQR 49-68, range 40-85) and mean body-mass index (BMI) of 25·6 kg/m(2) (SD 4·1). Participants underwent complete polysomnographic recordings at home and had extensive phenotyping for diabetes, hypertension, metabolic syndrome, and depression. The primary outcome was prevalence of sleep-disordered breathing, assessed by the apnoea-hypopnoea index. FINDINGS: The median apnoea-hypopnoea index was 6·9 events per h (IQR 2·7-14·1) in women and 14·9 per h (7·2-27·1) in men. The prevalence of moderate-to-severe sleep-disordered breathing (≥15 events per h) was 23·4% (95% CI 20·9-26·0) in women and 49·7% (46·6-52·8) in men. After multivariable adjustment, the upper quartile for the apnoea-hypopnoea index (>20·6 events per h) was associated independently with the presence of hypertension (odds ratio 1·60, 95% CI 1·14-2·26; p=0·0292 for trend across severity quartiles), diabetes (2·00, 1·05-3·99; p=0·0467), metabolic syndrome (2·80, 1·86-4·29; p<0·0001), and depression (1·92, 1·01-3·64; p=0·0292). INTERPRETATION: The high prevalence of sleep-disordered breathing recorded in our population-based sample might be attributable to the increased sensitivity of current recording techniques and scoring criteria. These results suggest that sleep-disordered breathing is highly prevalent, with important public health outcomes, and that the definition of the disorder should be revised. FUNDING: Faculty of Biology and Medicine of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, Ligue Pulmonaire Vaudoise

Associations of specific phobia and its subtypes with physical diseases: an adult community study.

Specific phobia is the most prevalent anxiety disorder in the community and is associated with substantial impairment. Comorbidity with physical diseases is assumed and has important implications for etiology, treatment, or prevention of the comorbid conditions. However, due to methodological issues data are limited and subtypes of specific phobia have not been investigated yet. We examined the association of specific phobia and its subtypes with physical diseases in a representative community sample with physician-diagnosed physical diseases and diagnostic criteria of specific phobia. Data of the German Mental Health Survey from 4181 subjects aged 18-65 years were used. Specific phobia was diagnosed using M-CIDI/DIA-X interview; physical diseases were assessed through a self-report questionnaire and a medical interview. Logistic regression analyses adjusted for sex were calculated. Specific phobia was associated with cardiac diseases, gastrointestinal diseases, respiratory diseases, arthritic conditions, migraine, and thyroid diseases (odds ratios between 1.49 and 2.53). Among the subtypes, different patterns of associations with physical diseases were established. The findings were partially replicated in the Swiss PsyCoLaus Study. Our analyses show that subjects with specific phobia have an increased probability for specific physical diseases. From these analyses etiological mechanisms of specific phobia and physical disease can be deduced. As subtypes differed in their patterns of associations with physical diseases, different etiological mechanisms may play a role. The findings are highly relevant for public health in terms of prevention and therapy of the comorbid conditions

Digital Signal Processing

Contains table of contents for Part III, table of contents for Section 1, an introduction and reports on seventeen research projects.National Science Foundation FellowshipNational Science Foundation (Grant ECS 84-07285)National Science Foundation (Grant MIP 87-14969)U.S. Navy - Office of Naval Research (Contract N00014-81-K-0742)Scholarship from the Federative Republic of BrazilU.S. Air Force - Electronic Systems Division (Contract F19628-85-K-0028)AT&T Bell Laboratories Doctoral Support ProgramCanada, Bell Northern Research ScholarshipCanada, Fonds pour la Formation de Chercheurs et I'Aide a la Recherche Postgraduate FellowshipSanders Associates, Inc.OKI Semiconductor, Inc.Tel Aviv University, Department of Electronic SystemsU.S. Navy - Office of Naval Research (Contract N00014-85-K-0272)Natural Sciences and Engineering Research Council of Canada, Science and Engineering Scholarshi