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A Concise History of Albania charts the history of Albania and its people, within their Balkan and European contexts. It shows the country's journey from its ancient past, still shrouded in mystery and controversy, through its difficult transition from a particularly brutal form of communism to an evolving form of democracy and a market economy. Bernd Fischer and Oliver Schmitt challenge some of the traditional narratives concerning the origins of the Albanians, and the relations between Albanians and their Balkan neighbours. This authoritative and up-to-date single-volume history analyses the political, social, economic, and cultural developments which led to the creation of the Albanian state and the modern nation, as well as Albania's more recent experience with authoritarianism, war, and communism. It greatly contributes to our understanding of the challenges facing contemporary Albanians, as well as the issues confronting the region as a whole as it attempts to grapple with one of the last remaining significant ethnic issues in the Balkans.
No single environmental factor is a necessary or sufficient cause of mental disorder; multifactorial and transdiagnostic approaches are needed to understand the impact of the environment on the development of mental disorders across the life course.
Using linked multi-agency administrative data for 71 932 children from the New South Wales Child Developmental Study, using logistic regression, we examined associations between 16 environmental risk factors in early life (prenatal period to <6 years of age) and later diagnoses of mental disorder recorded in health service data (from age 6 to 13 years), both individually and summed as an environmental risk score (ERS).
The ERS was associated with all types of mental disorder diagnoses in a dose–response fashion, such that 2.8% of children with no exposure to any of the environmental factors (ERS = 0), compared to 18.3% of children with an ERS of 8 or more indicating exposure to 8 or more environmental factors (ERS ⩾ 8), had been diagnosed with any type of mental disorder up to age 13–14 years. Thirteen of the 16 environmental factors measured (including prenatal factors, neighbourhood characteristics and more proximal experiences of trauma or neglect) were positively associated with at least one category of mental disorder.
Exposure to cumulative environmental risk factors in early life is associated with an increased likelihood of presenting to health services in childhood for any kind of mental disorder. In many instances, these factors are preventable or capable of mitigation by appropriate public policy settings.
The COVID-19 pandemic has rapidly accelerated the use of online and remote mental healthcare provision. The immediate need to transform services has not allowed for thorough examination of the literature supporting remote delivery of psychiatric care. In this article we review the history of telepsychiatry, the rationale for continuing to offer services remotely and the limitations of psychiatry without in-person care. Focusing on randomised controlled trials we find that evidence for the efficacy of remotely delivered psychiatric care compared with in-person treatment is of low quality and limited scope but does not demonstrate clear superiority of one care delivery method over the other.
We investigated risk factors associated with COVID-19 by conducting a retrospective, frequency-matched case-control study, with three sampling periods (August–October 2020). We compared cases completing routine contact tracing to asymptomatic population controls. Multivariable analyses estimated adjusted odds ratios (aORs) for non-household community settings. Meta-analyses using random effects provided pooled odds ratios (pORs). Working in healthcare (pOR 2.87; aORs 2.72, 2.81, 3.08, for study periods 1–3 respectively), social care (pOR 4.15; aORs 2.46, 5.06, 5.41, for study periods 1–3 respectively) or hospitality (pOR 2.36; aORs 2.01, 2.54, 2.63, for study periods 1–3 respectively) were associated with increased odds of being a COVID-19 case. Additionally, working in bars, pubs and restaurants, warehouse settings, construction, educational settings were significantly associated. While definitively determining where transmission occurs is impossible, we provide evidence that in certain sectors, the impact of mitigation measures may only be partial and reinforcement of measures should be considered in these settings.
In a 1916 paper, Ramanujan studied the additive convolution
of sum-of-divisors functions
, and proved an asymptotic formula for it when a and b are positive odd integers. He also conjectured that his asymptotic formula should hold for all positive real a and b. Ramanujan’s conjecture was subsequently proved by Ingham, and then by Halberstam with a power saving error term.
In this paper, we give a new proof of Ramanujan’s conjecture that obtains lower order terms in the asymptotics for most ranges of the parameters. We also describe a connection to a counting problem in geometric topology that was studied in the second author’s thesis and which served as our initial motivation in studying this sum.
OBJECTIVES/GOALS: Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients prognosis. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. METHODS/STUDY POPULATION: Current predictive models for GBC outcomes often utilize clinical data only. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Rochester, Minnesota, Daegu, Korea, Vilnius, Lithuania, and Calgary, Canada. We will perform next-generation RNA sequencing on these tissue samples. The patients clinical, pathologic and survival data will be abstracted from the medical record. Random forests, support vector machines, and gradient boosting machines will be applied to train the data. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis of next generation RNA sequencing from 18 GBC tissue samples identified recurrent mutations in genes enriched in pathways in cytoskeletal signaling, cell organization, cell movement, extracellular matrix interaction, growth, and proliferation. The top three most significantly altered pathways, actin cytoskeleton signaling, hepatic fibrosis/hepatic stellate cell activation, and epithelial adherens junction signaling, emphasized a molecular metastatic and invasive fingerprint in our patient cohort. This molecular fingerprint is consistent with the previous knowledge of the highly metastatic nature of gallbladder tumors and is also manifested physiologically in the patient cohort. DISCUSSION/SIGNIFICANCE: Integrative analysis of molecular and clinical characterization of GBC has not been fully established, and minimal improvement has been made to the survival of these patients. If overall survival can be better predicted, we can gain a greater understanding of key biomarkers driving the tumor phenotype.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Many mental disorders, including depression, bipolar disorder and schizophrenia, are associated with poor dietary quality and nutrient intake. There is, however, a deficit of research looking at the relationship between obsessive–compulsive disorder (OCD) severity, nutrient intake and dietary quality.
This study aims to explore the relationship between OCD severity, nutrient intake and dietary quality.
A post hoc regression analysis was conducted with data combined from two separate clinical trials that included 85 adults with diagnosed OCD, using the Structured Clinical Interview for DSM-5. Nutrient intakes were calculated from the Dietary Questionnaire for Epidemiological Studies version 3.2, and dietary quality was scored with the Healthy Eating Index for Australian Adults – 2013.
Nutrient intake in the sample largely aligned with Australian dietary guidelines. Linear regression models adjusted for gender, age and total energy intake showed no significant associations between OCD severity, nutrient intake and dietary quality (all P > 0.05). However, OCD severity was inversely associated with caffeine (β = −15.50, 95% CI −28.88 to −2.11, P = 0.024) and magnesium (β = −6.63, 95% CI −12.72 to −0.53, P = 0.034) intake after adjusting for OCD treatment resistance.
This study showed OCD severity had little effect on nutrient intake and dietary quality. Dietary quality scores were higher than prior studies with healthy samples, but limitations must be noted regarding comparability. Future studies employing larger sample sizes, control groups and more accurate dietary intake measures will further elucidate the relationship between nutrient intake and dietary quality in patients with OCD.
The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production and secretion of pro-inflammatory chemocytokines that overall dampen the pro-labour uteroplacental environment responsible for labour onset and progress, thus reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Clozapine is the most effective antipsychotic for treatment resistant schizophrenia but adverse reactions to clozapine include neutropenia. Patients with COVID-19 infection frequently experience lymphopenia, but not neutropenia.The impact of clozapine treatment in the presence of COVID-19 is unknown
Show 2 cases of neutropenia in patients treated with long-term clozapine during COVID-19 infection.
Subjects: 48 admitted patients to a long-stay psychiatric unit. COVID-19 infection confirmed by positive nasopharyngeal swab for viral ribonucleic acid of SARS-CoV-2. Hematological controls between March and April 2020.
16 patients (33%) treated with clozapine.18 patients (37’5%) had COVID-19 infection, of which 5 (10’4%) were treated with clozapine; 2 presented neutropenia. 1- 56-year-old woman diagnosed with schizophrenia on clozapine since 2009. Begins to have a dry cough and fever with positive COVID-19 swab (day 0). Slight leukopenia without neutropenia was observed on day 1. On day 7, neutropenia was observed with an absolute neutrophil count (ANC) of 1100. We decided to suspend clozapine and to initiate daily hematological controls. The ANC on day 8 was 970. Over the next few days the ANC will progressively improve until neutropenia resolved (day 22). 2- 55-year-old woman who required a transfer to a general hospital because of respiratory complications from COVID-19. She presented significant leukopenia (1’01x 10^3/uL) and neutropenia (ANC 100). Clozapine was not withdrawn. She was treated with granulocyte colony-stimulating factor.
An urgent full blood count will be required to exclude neutropenia with appropriate action. Further research will be needed to clarify the possible relationship between COVID-19, clozapine and neutropenia.
The Cognitive Disorders Unit carries out sessions of Psychoeducational Groups (PG) for caregivers of patients diagnosed with cognitive impairment (CI). The aim is to educate about the disease, improve the caregiver’s self-care and learn how to take better care of the sick.
Analyze the profile of the caregivers that participate in PG and assess changes in their psychological state.
Subjects: 110 caregivers of patients diagnosed with mild-moderate CI who have participated in PG. Methodology: sociodemographic data of the caregiver and patient are collected. The following scales are passed: General-Health-Questionnaire (GHQ-12), Global-Deterioration-Scale, Barthel-Index. 5 sessions of 90 minutes are carried out every fortnight. An opinion questionnaire and the GHQ-12 are administered at the end of the sessions.
86% of caregivers are women: 37% spouses and 55% daughters; mean age 57; 92% of patients live with the caregiver. 62% of caregivers present some kind of psychological disorder that is significantly reduced (p=0,0003) after some sessions. After PG: 65% of caregivers are able to further enjoy their daily activities 46% improve concentration capacity 42% improve sleeping and mood. Opinion Questionnaire Results: 98% of caregivers are satisfied with the activities, the topics addressed and their applicability.
The participants in PG were mostly daughters of patients, with average age 57, and living in the same household. Participation in PG improves the information and skills of caregivers, and reduces psychological disorders by improving their mood, their ability to concentrate, their quality of sleep and enjoyment of daily activities.