An overview of clustering methods with guidelines for application in mental health research

Cluster analyzes have been widely used in mental health research to decompose inter-individual heterogeneity by identifying more homogeneous subgroups of individuals. However, despite advances in new algorithms and increasing popularity, there is little guidance on model choice, analytical framework and reporting requirements. In this paper, we aimed to address this gap by introducing the philosophy, design, advantages/disadvantages and implementation of major algorithms that are particularly relevant in mental health research. Extensions of basic models, such as kernel methods, deep learning, semi-supervised clustering, and clustering ensembles are subsequently introduced. How to choose algorithms to address common issues as well as methods for pre-clustering data processing, clustering evaluation and validation are then discussed. Importantly, we also provide general guidance on clustering workflow and reporting requirements. To facilitate the implementation of different algorithms, we provide information on R functions and librarie

Social disadvantage in early psychosis and its effect on clinical presentation and service access, engagement and use

Incidence of psychosis varies geographically due to factors such as social disadvantage. Whether this influences the clinical presentation and/or engagement of those experiencing psychosis remains relatively understudied. This study analysed data from young people across Australia accessing ultra-high risk (UHR) or first episode psychosis (FEP) services delivered through the headspace Early Psychosis (hEP) program between June 2017 and March 2021. The cohort was categorised into low, middle, and high tertiles of social disadvantage using the Index of Relative Socioeconomic Disadvantage (IRSD). Data from 3089 participants aged 15–25 were included (1515 UHR, 1574 FEP). The low and middle tertiles for both cohorts had greater percentages of those not in education or employment (NEET), with First Nations or culturally and linguistically diverse backgrounds. Clinical presentations to services were similar across all tertiles in both cohorts, however, functioning at presentation varied significantly within the FEP cohort. Significantly lower numbers of direct services were provided in the low tertile of both cohorts, with significantly poorer engagement in the initial three-months also occurring for these young people. This variation in early psychosis service patterns associated with geographical variation in social deprivation demonstrates the need for further research and fine tuning of national early psychosis services.</p

A prototype software framework for transparent, reusable and updatable computational health economic models

Most health economic analyses are undertaken with the aid of computers. However, the ethical dimensions of implementing health economic models as software (or computational health economic models (CHEMs)) are poorly understood. We propose that developers and funders of CHEMs share ethical responsibilities to (i) establish socially acceptable user requirements and design specifications; (ii) ensure fitness for purpose; and (iii) support socially beneficial use. We further propose that a transparent (T), reusable (R) and updatable (U) CHEM is suggestive of a project team that has largely fulfilled these responsibilities. We propose six criteria for assessing CHEMs: (T1) software files are open access; (T2) project team contributions and judgments are easily identified; (R1) programming practices promote generalisability and transferability; (R2) licenses restrict only unethical reuse; (U1) maintenance infrastructure is in place; and (U2) new releases are systematically retested and appropriately deprecated. To facilitate CHEMs that meet TRU criteria, we have developed a prototype software framework in the open-source programming language R. The framework comprises six code libraries for authoring CHEMs, supplying CHEMs with data and undertaking analyses with CHEMs. The prototype software framework integrates with services for software development and research data archiving. We determine that an initial set of youth mental health CHEMs we developed with the prototype software framework wholly meet criteria T1-2, R1-2 and U1 and partially meet criterion U2. Our assessment criteria and prototype software framework can help inform and improve ethical implementation of CHEMs. Resource barriers to ethical CHEM practice should be addressed by research funders.Comment: 17 pages, 4 tables, 1 figur

Heterogeneity of quality of life in young people attending primary mental health services

AIMS: The utility of quality of life (QoL) as an outcome measure in youth-specific primary mental health care settings has yet to be determined. We aimed to determine: (i) whether heterogeneity on individual items of a QoL measure could be used to identify distinct groups of help-seeking young people; and (ii) the validity of these groups based on having clinically meaningful differences in demographic and clinical characteristics. METHODS: Young people, at their first presentation to one of five primary mental health services, completed a range of questionnaires, including the Assessment of Quality of Life–6 dimensions adolescent version (AQoL-6D). Latent class analysis (LCA) and multivariate multinomial logistic regression were used to define classes based on AQoL-6D and determine demographic and clinical characteristics associated with class membership. RESULTS: 1107 young people (12–25 years) participated. Four groups were identified: (i) no-to-mild impairment in QoL; (ii) moderate impairment across dimensions but especially mental health and coping; (iii) moderate impairment across dimensions but especially on the pain dimension; and (iv) poor QoL across all dimensions along with a greater likelihood of complex and severe clinical presentations. Differences between groups were observed with respect to demographic and clinical features. CONCLUSIONS: Adding multi-attribute utility instruments such as the AQoL-6D to routine data collection in mental health services might generate insights into the care needs of young people beyond reducing psychological distress and promoting symptom recovery. In young people with impairments across all QoL dimensions, the need for a holistic and personalised approach to treatment and recovery is heightened

Associations Between Dysmenorrhea Symptom-Based Phenotypes and Vaginal Microbiome: A Pilot Study

BACKGROUND: Dysmenorrhea is highly prevalent; it places women at risk for other chronic pain conditions. There is a high degree of individual variability in menstrual pain severity, the number of painful sites, and co-occurring gastrointestinal symptoms. Distinct dysmenorrhea symptom-based phenotypes were previously identified, but the biological underpinnings of these phenotypes are less known. One underexplored contributor is the vaginal microbiome. The vaginal microbiota differs significantly among reproductive-age women and may modulate as well as amplify reproductive tract inflammation, which may contribute to dysmenorrhea symptoms. OBJECTIVES: The objective of this study was to examine associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome compositions on- and off-menses. METHODS: We conducted a prospective, longitudinal, pilot study of 20 women (aged 15-24 years) grouped into three dysmenorrhea symptom-based phenotypes: "mild localized pain," "severe localized pain," and "severe multiple pain and gastrointestinal symptoms." Over one menstrual cycle, participants provided vaginal swabs when they were on- and off-menses. We assayed the vaginal microbiome using 16S rRNA gene sequencing. Permutational multivariate analysis of variance tests were used to compare microbiome compositions across phenotypes, with heat maps generated to visualize the relative abundance of bacterial taxa. RESULTS: The vaginal microbiome compositions (n = 40) were different across the three phenotypes. After separating the on-menses (n = 20) and off-menses (n = 20) specimens, the statistically significant difference was seen on-menses, but not off-menses. Compared to the "mild localized pain" phenotype, participants in the "multiple severe symptoms" phenotype had a lower lactobacilli level and a higher abundance of Prevotella, Atopobium, and Gardnerella when on-menses. We also observed trends of differences across phenotypes in vaginal microbiome change from off- to on-menses. DISCUSSION: The study provides proof-of-concept data to support larger studies on associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome that might lead to new intervention targets and/or biomarkers for dysmenorrhea. This line of research has the potential to inform precision dysmenorrhea treatment that can improve women's quality of life

Climate change concerns impact on young Australians’ psychological distress and outlook for the future

Aims: Climate change is escalating and will disproportionately affect young people. Research on the mental health consequences of worry or concerns related to climate change are so far limited. This study aims to evaluate the extent of climate change concern in young people aged 15–19, its association with various demographic factors and its impact on psychological distress and future outlook. Understanding the impact of climate concerns on young people's mental wellbeing is crucial for identifying effective measures and building resilience. Methods: Climate concerns, psychological distress, and future outlook were measured in the 2022 Mission Australia Youth Survey, Australia's largest annual population-wide survey of young people aged 15 to 19 (N = 18,800). Multinomial logistic regression models were used to map factors associated with climate concerns and assess whether climate concerns are associated with psychological distress and future outlook. Results: One in four young people reported feeling very or extremely concerned about climate change. Climate concerns were higher among individuals identifying as female or gender diverse, or who self-reported a mental health condition. After controlling for confounding factors, we found those who were very or extremely concerned about climate change to be more likely to have high psychological distress than those not at all concerned (Relative risk ratio (RRR) = 1.81; 95% CI: 1.56–2.11), and more likely to have a negative future outlook (RRR = 1.52; 95% CI: 1.27–1.81). These associations were stronger among participants who reported to be gender diverse, Indigenous or from outer-regional/remote areas. Conclusion: This study identified associations between climate concerns, psychological distress, and future outlook among young people. Immediate attention from research and policy sectors to support climate change education, communication strategies and targeted interventions is urgently required to mitigate long-term impacts on young people's wellbeing.</p

From the cell membrane to the nucleus: unearthing transport mechanisms for Dynein

Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-Marie-Tooth disease, spinal muscular atrophy, and severe intellectual disabilities in humans. In mouse models, neurodegeneration is observed. We sought to develop a novel model which could incorporate the effects of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments

Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age

The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2(BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3–34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45–1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60–3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiotherapy

MicroRNA-224 Targets SMAD Family Member 4 to Promote Cell Proliferation and Negatively Influence Patient Survival

10.1371/journal.pone.0068744PLoS ONE87-POLN

THE ANALYSIS OF PUNCTUATION USE IN UNPUNCTUATED PASSAGES: A DISCOURSE-GRAPHOLOGY PERSPECTIVE

Diski Eginda Rismianti. 14111310149. The Analysis of Punctuation Use in Unpunctuated Passages: A Discourse-Graphology Perspective. Punctuation is the basic element in writing which is important to clarify meaning. Without punctuation or ignoring the rule of punctuation in a passage, the writing will be ambiguous. The writing course in IAIN Syekh Nurjati Cirebon is studied by English Student in 5 levels. Based the phenomenon, this research aims to find out the students’ error in the use of punctuation and how does the use relate to the meaning of restrictive and nonrestrictive elements. The analyses process in this research is constructed based on the theory from Marcella Frank. This research used qualitative method in analyzing data where the data contains the two original passages which is taken from the book of academic writing and the three participants’ work which are got by examining the passages as a main data source to be analyzed in this research. Those passages are changed be unpunctuated passages then examined to the 3 EFL learner which comes from the high score, medium score, and low score of writing. The result of this analysis shows that there are fifteen punctuation marks which are used in the two passages; they are capitalization, periods, commas, semicolons, colons, quotation marks, parentheses, apostrophes, hyphen, en dashes, ellipses, percent, underscore, at sign, and citation. FP has highest number of error in Capitalization with 100%. SP has big problem in commas exactly in the nineteenth rule with 90% and TP are wrong in parentheses. For restrictive and nonrestrictive elements, restrictive elements has higher number than nonrestrictive elements, except is in appositive. The numbers of the elements are same with the three participants. The differences come from the number of appositive which passages has higher number of nonrestrictive appositive than restrictive appositives. The results show that punctuation in unpunctuated passages used the rule from APA (American Psychological Association). The effects of the use of punctuation are in the number of sentences and clauses, types of phrases, and restrictive and nonrestrictive elements. For the students’ error, there are some sentences in FP and TP which only contain phrase. Key words: Punctuation Marks, Restrictive and Nonrestrictive Clause, Restrictive and Nonrestrictive Phrase, Restrictive and Nonrestrictive Appositives