Transcranial sonothrombolysis using high-intensity focused ultrasound: impact of increasing output power on clot fragmentation

Abstract Background The primary goal of this study was to investigate the relationship between increasing output power levels and clot fragmentation during high-intensity focused ultrasound (HIFU)-induced thrombolysis. Methods A HIFU headsystem, designed for brain applications in humans, was used for this project. A human calvarium was mounted inside the water-filled hemispheric transducer. Artificial thrombi were placed inside the skull and located at the natural focus point of the transducer. Clots were exposed to a range of acoustic output power levels from 0 to 400 W. The other HIFU operating parameters remained constant. To assess clot fragmentation, three filters of different mesh pore sizes were used. To assess sonothrombolysis efficacy, the clot weight loss was measured. Results No evidence of increasing clot fragmentation was found with increasing acoustic intensities in the majority of the study groups of less than 400 W. Increasing clot lysis could be observed with increasing acoustic output powers. Conclusion Transcranial sonothrombolysis could be achieved in vitro within seconds in the absence of tPA and without producing relevant clot fragmentation, using acoustic output powers of \u3c400 W

The UniWellbeing course: A randomised controlled trial of a transdiagnostic internet-delivered cognitive behavioural therapy (CBT) programme for university students with symptoms of anxiety and depression

AbstractAnxiety and depression are prevalent among university students and many universities offer psychological services to assist students. Unfortunately, students can experience barriers that prevent access to these services and many university services experience difficulties meeting demand. The present pragmatic randomised controlled trial examined the preliminary efficacy and acceptability of a transdiagnostic and internet-delivered cognitive behavioural therapy (CBT) programme for university students seeking help with anxiety and depression. Participants were randomly allocated to either a treatment group (n=30) or a waitlist-control group (n=23). The treatment group received weekly contact with a therapist, via telephone or a secure messaging system, as well as automated emails that guided their progress through the programme. Significant reductions were found on standard measures of anxiety (Cohen's d=0.66; 95% CI: 0.13 to 1.17) and depression (Cohen's d=0.81; 95% CI: 0.27 to 1.32) among the treatment group participants, but no significant differences were found between the treatment and control groups at post-treatment. However, more pronounced reductions were found among treatment group participants with clinical level symptoms of anxiety (Cohen's d=1.33; 95% CI: 0.62 to 1.99) and depression (Cohen's d=1.59; 95% CI: 0.81 to 2.30), who reported significantly lower levels of symptoms than control group participants at post-treatment. These reductions were maintained at 3-month follow-up and participants rated the intervention as acceptable. The results provide preliminary support for the potential of iCBT for university students with anxiety and depression. However, larger scale implementation trials considering a broader range of outcomes are required.Trial registrationAustralian and New Zealand Clinical Trials Registry: ACTRN12612000212853

Isolation and Phylogenetic Grouping of Equine Encephalosis Virus in Israel

During 2008–2009 in Israel, equine encephalosis virus (EEV) caused febrile outbreaks in horses. Phylogenetic analysis of segment 10 of the virus strains showed that they form a new cluster; analysis of segment 2 showed ≈92% sequence identity to EEV-3, the reference isolate. Thus, the source of this emerging EEV remains uncertain

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Generating and interpreting evidence from psychotherapy: An examination of measurement models, missing cases, and classification methods

Thesis by publication.Includes bibliographic references.Chapter 1. General introduction -- Chapter 2. Measurement of symptom change following web-based psychotherapy: statistical characteristics and analytical methods for measuring and interpreting change (study 1) -- Chapter 3. Statistical characteristics and analytical methods for measuring and interpreting symptom change in psychotherapy - a replication and elaboration study (study 2) -- Chapter 4. "Wish you were here": examining characteristics, outcomes, and statistical solutions for missing cases in web-based psychotherapeutic trials (study 3) -- Chapter 5. Examining characteristics, outcomes, and statistical solutions for missing cases in web-based psychotherapeutic trials - a replication and extension (study 4) -- Chapter 6. Classification of symptom improvement in psychotherapy: A new proposed approach for classifying minimal treatment-related response (Min-TR) (study 5) -- Chapter 7. General discussion -- AppendicesThe primary aim of this thesis is to explore and identify some of the statistical assumptions that underpin the measurement, statistical analysis, and interpretation of the effects of psychotherapy for anxiety and depression. The identification of these statistical assumption are then used to reflect on the suitability of common statistical techniques that underpin quantitative psychotherapy research and treatment evaluation. A series of five studies are presented, exploring the different statistical assumptions that underpin the measurement of symptom change through treatment (Studies 1 and 2), the handling of missing cases (Studies 3 and 4), and the classification of symptom outcomes into categories that represent the individual impact of treatment (Studies 5). The clinical datasets employed in these studies are comprised from samples of participants enrolled in randomised controlled trials (n>820) or patients enrolled in routine care (n>6700), who receive internet-delivered cognitive behavioural therapy (iCBT) for anxiety and depression. The iCBT context is used as an exemplar psychotherapy context, with highly protocolised procedures which reduces measurement variance due to therapy type or therapist. The results of these studies, identify several statistical assumptions that seem to generalise across psychotherapy data; being the proportional reduction of symptom change, the assumption of missing at random that is conditional on treatment adherence, and the occurrence of proportional symptom change that is non-specific to treatment. These results also indicate that the use of conventional methods for reporting treatment efficacy, including Cohen's d effect size and the Reliable Change Index (RCI), and for statistically adjusting for data missing from clinical trials,including the missing completely at random assumption (MCAR), may result in error in evaluation and interpretation. Each of the five studies also point to the benefits of selecting alternative statistical methods that better fit the context of psychotherapy data, reduce measurement error, and increase the ability to interpret clinical change with increased validity. As a body of work, the thesis seeks to point to a set of methods that strike a balance between the competing priorities of researchers to select methods that fit the specific nuances of psychotherapy data, and the selection of methods that enable the comparison and generalisability of psychotherapy outcomes across different contexts (e.g. different symptom scales and treatment types). The research of this thesis is explored through both statistical and clinical viewpoints but is primarily written and directed for clinical researchers and a clinical audience. Implications for the broader field of mental health research are also discussed.Mode of access: Internet.1 online resource (xvi, 230 pages

Facebook as an effective recruitment strategy for mental health research of hard to reach populations

Recent reports indicate that Facebook (FB) may facilitate recruitment of hard to reach participants into mental health research. The present study aimed to contribute to this emerging literature by exploring recruitment data from a recently completed trial of online treatment for symptoms of anxiety and depression that targeted Arab people. The present study compared traditional recruitment strategies such as media releases, emails, and print advertisements with Facebook strategies including boosting posts, promoting websites, events and FB public fan pages. The main outcomes of interest were the number of started applications and the time and cost per application associated with the FB and traditional recruitment strategies. A target sample of 350 was sought and a total of 81 participants applied to participate over the 42-week recruitment period. Overall, 86% of the resultant applications occurred via FB recruitment and a Poisson regression analysis indicated the FB strategies were more time-effective, recruiting participants 2.5 times faster than the traditional strategies. However, there were no differences in cost-effectiveness for FB ($US37 per participant) and traditional strategies ($US40 per participant). The findings of the current study add to existing literature detailing the value of FB recruitment strategies, alongside more traditional strategies, as a way of recruiting hard-to-reach populations for research. However, more research is needed to explore alternative and optimal strategies for the successful recruitment of hard to reach populations via FB and other online social media platforms.10 page(s