Patterns, predictors, and patient-reported reasons for antidepressant discontinuation in the WHO World Mental Health Surveys.

BACKGROUND: Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation. METHODS: Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months. RESULTS: 10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation. CONCLUSION: Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.

Age of onset and cumulative risk of mental disorders: a cross-national analysis of population surveys from 29 countries.

BACKGROUND: Information on the frequency and timing of mental disorder onsets across the lifespan is of fundamental importance for public health planning. Broad, cross-national estimates of this information from coordinated general population surveys were last updated in 2007. We aimed to provide updated and improved estimates of age-of-onset distributions, lifetime prevalence, and morbid risk. METHODS: In this cross-national analysis, we analysed data from respondents aged 18 years or older to the World Mental Health surveys, a coordinated series of cross-sectional, face-to-face community epidemiological surveys administered between 2001 and 2022. In the surveys, the WHO Composite International Diagnostic Interview, a fully structured psychiatric diagnostic interview, was used to assess age of onset, lifetime prevalence, and morbid risk of 13 DSM-IV mental disorders until age 75 years across surveys by sex. We did not assess ethnicity. The surveys were geographically clustered and weighted to adjust for selection probability, and standard errors of incidence rates and cumulative incidence curves were calculated using the jackknife repeated replications simulation method, taking weighting and geographical clustering of data into account. FINDINGS: We included 156 331 respondents from 32 surveys in 29 countries, including 12 low-income and middle-income countries and 17 high-income countries, and including 85 308 (54·5%) female respondents and 71 023 (45·4%) male respondents. The lifetime prevalence of any mental disorder was 28·6% (95% CI 27·9-29·2) for male respondents and 29·8% (29·2-30·3) for female respondents. Morbid risk of any mental disorder by age 75 years was 46·4% (44·9-47·8) for male respondents and 53·1% (51·9-54·3) for female respondents. Conditional probabilities of first onset peaked at approximately age 15 years, with a median age of onset of 19 years (IQR 14-32) for male respondents and 20 years (12-36) for female respondents. The two most prevalent disorders were alcohol use disorder and major depressive disorder for male respondents and major depressive disorder and specific phobia for female respondents. INTERPRETATION: By age 75 years, approximately half the population can expect to develop one or more of the 13 mental disorders considered in this Article. These disorders typically first emerge in childhood, adolescence, or young adulthood. Services should have the capacity to detect and treat common mental disorders promptly and to optimise care that suits people at these crucial parts of the life course. FUNDING: None.

Findings From the World Mental Health Surveys of Civil Violence Exposure and Its Association With Subsequent Onset and Persistence of Mental Disorders.

Importance: Understanding the association of civil violence with mental disorders is important for developing effective postconflict recovery policies. Objective: To estimate the association between exposure to civil violence and the subsequent onset and persistence of common mental disorders (in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) in representative surveys of civilians from countries that have experienced civil violence since World War II. Design, Setting, and Participants: This study used data from cross-sectional World Health Organization World Mental Health (WMH) surveys administered to households between February 5, 2001, and January 5, 2022, in 7 countries that experienced periods of civil violence after World War II (Argentina, Colombia, Lebanon, Nigeria, Northern Ireland, Peru, and South Africa). Data from respondents in other WMH surveys who immigrated from countries with civil violence in Africa and Latin America were also included. Representative samples comprised adults (aged ≥18 years) from eligible countries. Data analysis was performed from February 10 to 13, 2023. Exposures: Exposure was defined as a self-report of having been a civilian in a war zone or region of terror. Related stressors (being displaced, witnessing atrocities, or being a combatant) were also assessed. Exposures occurred a median of 21 (IQR, 12-30) years before the interview. Main Outcomes and Measures: The main outcome was the retrospectively reported lifetime prevalence and 12-month persistence (estimated by calculating 12-month prevalence among lifetime cases) of DSM-IV anxiety, mood, and externalizing (alcohol use, illicit drug use, or intermittent explosive) disorders. Results: This study included 18 212 respondents from 7 countries. Of these individuals, 2096 reported that they were exposed to civil violence (56.5% were men; median age, 40 [IQR, 30-52] years) and 16 116 were not exposed (45.2% were men; median age, 35 [IQR, 26-48] years). Respondents who reported being exposed to civil violence had a significantly elevated onset risk of anxiety (risk ratio [RR], 1.8 [95% CI, 1.5-2.1]), mood (RR, 1.5 [95% CI, 1.3-1.7]), and externalizing (RR, 1.6 [95% CI, 1.3-1.9]) disorders. Combatants additionally had a significantly elevated onset risk of anxiety disorders (RR, 2.0 [95% CI, 1.3-3.1]) and refugees had an increased onset risk of mood (RR, 1.5 [95% CI, 1.1-2.0]) and externalizing (RR, 1.6 [95% CI, 1.0-2.4]) disorders. Elevated disorder onset risks persisted for more than 2 decades if conflicts persisted but not after either termination of hostilities or emigration. Persistence (ie, 12-month prevalence among respondents with lifetime prevalence of the disorder), in comparison, was generally not associated with exposure. Conclusions: In this survey study of exposure to civil violence, exposure was associated with an elevated risk of mental disorders among civilians for many years after initial exposure. These findings suggest that policy makers should recognize these associations when projecting future mental disorder treatment needs in countries experiencing civil violence and among affected migrants.

The associations between traumatic experiences and subsequent onset of a substance use disorder: Findings from the World Health Organization World Mental Health surveys.

AIM: Exposure to traumatic events (TEs) is associated with substance use disorders (SUDs). However, most studies focus on a single TE, and are limited to single countries, rather than across countries with variation in economic, social and cultural characteristics. We used cross-national data to examine associations of diverse TEs with SUD onset, and variation in associations over time. METHODS: Data come from World Mental Health surveys across 22 countries. Adults (n = 65,165) retrospectively reported exposure to 29 TEs in six categories: "exposure to organised violence"; "participation in organised violence"; "interpersonal violence"; "sexual-relationship violence"; "other life-threatening events"; and those involving loved ones ("network traumas"). Discrete-time survival analyses were used to examine associations with subsequent first SUD onset. RESULTS: Most (71.0%) reported experiencing at least one TE, with network traumas (38.8%) most common and exposure to organised violence (9.5%) least. One in five (20.3%) had been exposed to sexual-relationship violence and 26.6% to interpersonal violence. Among the TE exposed, lifetime SUD prevalence was 14.5% compared to 5.1% with no trauma exposure. Most TE categories (except organised violence) were associated with increased odds of SUD. Increased odds of SUD were also found following interpersonal violence exposure across all age ranges (ORs from 1.56 to 1.78), and sexual-relationship violence exposure during adulthood (ORs from 1.33 to 1.44), with associations persisting even after >11 years. CONCLUSION: Sexual and interpersonal violence have the most consistent associations with progression to SUD; increased risk remains for many years post-exposure. These need to be considered when working with people exposed to such traumas.

Increased risks for mental disorders among LGB individuals: cross-national evidence from the World Mental Health Surveys.

PURPOSE: Lesbian, gay, and bisexual (LGB) individuals, and LB women specifically, have an increased risk for psychiatric morbidity, theorized to result from stigma-based discrimination. To date, no study has investigated the mental health disparities between LGB and heterosexual AQ1individuals in a large cross-national population-based comparison. The current study addresses this gap by examining differences between LGB and heterosexual participants in 13 cross-national surveys, and by exploring whether these disparities were associated with country-level LGBT acceptance. Since lower social support has been suggested as a mediator of sexual orientation-based differences in psychiatric morbidity, our secondary aim was to examine whether mental health disparities were partially explained by general social support from family and friends. METHODS: Twelve-month prevalence of DSM-IV anxiety, mood, eating, disruptive behavior, and substance disorders was assessed with the WHO Composite International Diagnostic Interview in a general population sample across 13 countries as part of the World Mental Health Surveys. Participants were 46,889 adults (19,887 males; 807 LGB-identified). RESULTS: Male and female LGB participants were more likely to report any 12-month disorder (OR 2.2, p < 0.001 and OR 2.7, p < 0.001, respectively) and most individual disorders than heterosexual participants. We found no evidence for an association between country-level LGBT acceptance and rates of psychiatric morbidity between LGB and heterosexualAQ2 participants. However, among LB women, the increased risk for mental disorders was partially explained by lower general openness with family, although most of the increased risk remained unexplained. CONCLUSION: These results provide cross-national evidence for an association between sexual minority status and psychiatric morbidity, and highlight that for women, but not men, this association was partially mediated by perceived openness with family. Future research into individual-level and cross-national sexual minority stressors is needed.

A Multi-Site Assessment of Anesthetic Overdose, Hypothermic Shock, and Electrical Stunning as Methods of Euthanasia for Zebrafish (Danio rerio) Embryos and Larvae.

Euthanasia in zebrafish (Danio rerio) younger than 5 days post fertilization (dpf) is poorly described in the literature, and standardized protocols are lacking, most likely because larvae not capable of independent feeding are often not protected under national legislations. We assessed the euthanasia efficacy in laboratories in different countries of a one hour anesthetic overdose immersion with buffered lidocaine hydrochloride (1 g/L, with or without 50 mL/L of ethanol), buffered tricaine (1 g/L), clove oil (0.1%), benzocaine (1 g/L), or 2-phenoxyethanol (3 mL/L), as well as the efficacy of hypothermic shock (one hour immersion) and electrical stunning (for one minute), on zebrafish at <12 h post fertilization (hpf), 24 hpf, and 4 dpf. Based on the survival/recovery rates 24 h after treatment, the most effective methods were clove oil, lidocaine with ethanol, and electrical stunning. For 4 dpf larvae, signs of aversion during treatment demonstrated that all anesthetics, except lidocaine, induced aversive behavior. Therefore, the most suited euthanasic treatment was lidocaine hydrochloride 1 g/L, buffered with 2 g/L of sodium bicarbonate and mixed with 50 mL/L of ethanol, which euthanized both embryos and larvae in an efficient and stress-free manner. Electrical stunning also euthanized embryos and larvae efficiently and without signs of aversion; this method needs further assessment in other laboratories to draw firm conclusions.

From Mating to Milk Access: A Review of Reproductive Vocal Communication in Mice.

Vocalisations play a central role in rodent communication, especially in reproduction related behaviours. In adult mice (Mus musculus) the emission of ultrasonic vocalisations (USVs) has been observed in courtship and mating behaviour, especially by males. These have been found to have distinctive individual signatures that influence female choice of mating partner. The most recent findings show that vocal communication also has a role in parental cooperation, in that female mice communicate with male partners in ultrasonic frequencies to induce paternal behaviour. Infant vocalisations form the other important part of reproductive vocal communication. Although born deaf, neonatal mice are capable of producing vocalisations since birth. As an altricial species, successful mother-infant communication is essential for survival, and these vocalisations are important modulators of maternal behaviour. Three main types of infant vocalisations have been identified and characterised. Most research has addressed pure USVs, related to stressful situations (e.g., cold, isolation, handling, presence of unfamiliar males or predators), which usually elicit maternal search and retrieval. In addition, broad-band spectrum signals, emitted post-partum during cleaning of foetal membranes, inhibit biting and injury by adults and "wriggling calls," emitted during suckling, release maternal behaviour (such as licking). Several variables have been identified to modulate vocalisations in mice, including individual characteristics such as strain/genotype, age, sex, and experimental factors such as pharmacological compounds and social context. In recent years, there has been a big increase in the knowledge about the characteristics of vocal communication in rodents due to recent technological advances as well as a growing interest from the neuroscience community. Vocalisation analysis has become an essential tool for phenotyping and evaluating emotional states. In this review, we will (i) provide a comprehensive summary of the current knowledge on mouse reproductive vocal communication and (ii) discuss the most recent findings in order to provide a broad overview on this topic.

Perceived helpfulness of treatment for social anxiety disorder: findings from the WHO World Mental Health Surveys.

PURPOSE: To investigate the prevalence and predictors of perceived helpfulness of treatment in persons with a history of DSM-IV social anxiety disorder (SAD), using a worldwide population-based sample. METHODS: The World Health Organization World Mental Health Surveys is a coordinated series of community epidemiological surveys of non-institutionalized adults; 27 surveys in 24 countries (16 in high-income; 11 in low/middle-income countries; N = 117,856) included people with a lifetime history of treated SAD. RESULTS: In respondents with lifetime SAD, approximately one in five ever obtained treatment. Among these (n = 1322), cumulative probability of receiving treatment they regarded as helpful after seeing up to seven professionals was 92.2%. However, only 30.2% persisted this long, resulting in 65.1% ever receiving treatment perceived as helpful. Perceiving treatment as helpful was more common in female respondents, those currently married, more highly educated, and treated in non-formal health-care settings. Persistence in seeking treatment for SAD was higher among those with shorter delays in seeking treatment, in those receiving medication from a mental health specialist, and those with more than two lifetime anxiety disorders. CONCLUSIONS: The vast majority of individuals with SAD do not receive any treatment. Among those who do, the probability that people treated for SAD obtain treatment they consider helpful increases considerably if they persisted in help-seeking after earlier unhelpful treatments.

Barriers to treatment for mental disorders in six countries of the Americas: A regional report from the World Mental Health Surveys.

BACKGROUND: Mental health treatment is scarce and little resources are invested in reducing the wide treatment gap that exists in the Americas. The regional barriers are unknown. We describe the barriers for not seeking treatment among those with mental and substance use disorders from six (four low- and middle-income and two high-income) countries from the Americas. Regional socio-demographic and clinical correlates are assessed. METHODS: Respondents (n = 4648) from seven World Mental Health surveys carried out in Argentina, Brazil, Colombia, Mexico, Peru, and the United States, who met diagnostic criteria for a 12-month mental disorder, measured with the Composite International Diagnostic Interview, and who did not access treatment, were asked about treatment need and, among those with need, structural and attitudinal barriers. Country-specific deviations from regional estimates were evaluated through logistic models. RESULTS: In the Americas, 43% of those that did not access treatment did not perceive treatment need, while the rest reported structural and attitudinal barriers. Overall, 27% reported structural barriers, and 95% attitudinal barriers. The most frequent attitudinal barrier was to want to handle it on their own (69.4%). Being female and having higher severity of disorders were significant correlates of greater perceived structural and lower attitudinal barriers, with few country-specific variations. LIMITATIONS: Only six countries in the Americas are represented; the cross-sectional nature of the survey precludes any causal interpretation. CONCLUSIONS: Awareness of disorder or treatment need in various forms is one of the main barriers reported in the Americas and it specially affects persons with severe disorders.

Dropout from treatment for mental disorders in six countries of the Americas: A regional report from the World Mental Health Surveys.

OBJECTIVE: To estimate structural and attitudinal reasons for premature discontinuation of mental health treatment, socio-demographic and clinical correlates of treatment dropout due to these reasons, and to test country differences from the overall effect across the region of the Americas. METHODS: World Health Organization-World Mental Health (WMH) surveys were carried out in six countries in the Americas: Argentina, Brazil, Colombia, Mexico, Peru and USA. Among the 1991 participants who met diagnostic criteria (measured with the Composite International Diagnostic Interview (WMHCIDI)) for a mental disorder and were in treatment in the prior 12-months, the 236 (12.2%) who dropped out of treatment before the professional recommended were included. FINDINGS: In all countries, individuals more frequently reported attitudinal (79.2%) rather than structural reasons (30.7%) for dropout. Disorder severity was associated with structural reasons; those with severe disorder (versus mild disorder) had 3.4 (95%CI=1.1-11.1) times the odds of reporting a structural reason. Regarding attitudinal reasons, those with lower income (versus higher income) were less likely to discontinue treatment because of getting better (OR=0.4; 95%CI= 0.2-0.9). Country specific variations were found. LIMITATIONS: Not all countries, or the poorest, in the region were included. Some estimations couldn´t be calculated due to cell size. Causality cannot be assumed. CONCLUSION: Clinicians should in the first sessions address attitudinal factors that may lead to premature termination. Public policies need to consider distribution of services to increase convenience. A more rational use of resources would be to offer brief therapies to individuals most likely to drop out of treatment prematurely.

Transdiagnostic development of internalizing psychopathology throughout the life course up to age 45: a World Mental Health Surveys report.

BACKGROUND: Depressive and anxiety disorders are highly comorbid, which has been theorized to be due to an underlying internalizing vulnerability. We aimed to identify groups of participants with differing vulnerabilities by examining the course of internalizing psychopathology up to age 45. METHODS: We used data from 24158 participants (aged 45+) in 23 population-based cross-sectional World Mental Health Surveys. Internalizing disorders were assessed with the Composite International Diagnostic Interview (CIDI). We applied latent class growth analysis (LCGA) and investigated the characteristics of identified classes using logistic or linear regression. RESULTS: The best-fitting LCGA solution identified eight classes: a healthy class (81.9%), three childhood-onset classes with mild (3.7%), moderate (2.0%), or severe (1.1%) internalizing comorbidity, two puberty-onset classes with mild (4.0%) or moderate (1.4%) comorbidity, and two adult-onset classes with mild comorbidity (2.7% and 3.2%). The childhood-onset severe class had particularly unfavorable sociodemographic outcomes compared to the healthy class, with increased risks of being never or previously married (OR = 2.2 and 2.0, p < 0.001), not being employed (OR = 3.5, p < 0.001), and having a low/low-average income (OR = 2.2, p < 0.001). Moderate or severe (v. mild) comorbidity was associated with 12-month internalizing disorders (OR = 1.9 and 4.8, p < 0.001), disability (B = 1.1-2.3, p < 0.001), and suicidal ideation (OR = 4.2, p < 0.001 for severe comorbidity only). Adult (v. childhood) onset was associated with lower rates of 12-month internalizing disorders (OR = 0.2, p < 0.001). CONCLUSIONS: We identified eight transdiagnostic trajectories of internalizing psychopathology. Unfavorable outcomes were concentrated in the 1% of participants with childhood onset and severe comorbidity. Early identification of this group may offer opportunities for preventive interventions.

Screening of Anaesthetics in Adult Zebrafish (Danio rerio) for the Induction of Euthanasia by Overdose.

Zebrafish are often euthanized by overdose of anaesthesia. However, fish may have aversion towards some anaesthetics, and protocol efficacy varies between species. Using wild type adult Danio rerio, we assessed time to loss of opercular beat, righting, and startle reflexes during induction of anaesthetic overdose by either tricaine (0.5 g/L or 1 g/L), benzocaine (1 g/L), 2-phenoxyethanol (3 mL/L), clove oil (0.1%), isoeugenol (540 mg/L), lidocaine hydrochloride (1 g/L), or etomidate (50 mg/L). Initial screening demonstrated that benzocaine and buffered lidocaine hydrochloride achieved the fastest loss of reflexes. The rapid induction times were confirmed when retesting using larger batches of fish. The fastest induction was obtained with 1 g/L lidocaine hydrochloride buffered with 2 g/L NaHCO3, in which all adult zebrafish lost reflexes in less than 2 min. Next, we monitored signs of distress during benzocaine or buffered lidocaine hydrochloride overdose induction. The results indicated that buffered lidocaine hydrochloride caused significantly less aversive behaviors than benzocaine. Finally, we tested several buffers to refine the lidocaine hydrochloride immersion. The most efficient buffer for euthanasia induction using 1g/L lidocaine hydrochloride was 2 g/L NaHCO3 with 50 mL/L 96% ethanol, inducing immobility in less than 10 s and with only 2% of adult zebrafish displaying aversive behaviors during treatment.

Previous disorders and depression outcomes in individuals with 12-month major depressive disorder in the World Mental Health surveys.

AIMS: Major depressive disorder (MDD) is characterised by a recurrent course and high comorbidity rates. A lifespan perspective may therefore provide important information regarding health outcomes. The aim of the present study is to examine mental disorders that preceded 12-month MDD diagnosis and the impact of these disorders on depression outcomes. METHODS: Data came from 29 cross-sectional community epidemiological surveys of adults in 27 countries (n = 80 190). The Composite International Diagnostic Interview (CIDI) was used to assess 12-month MDD and lifetime DSM-IV disorders with onset prior to the respondent's age at interview. Disorders were grouped into depressive distress disorders, non-depressive distress disorders, fear disorders and externalising disorders. Depression outcomes included 12-month suicidality, days out of role and impairment in role functioning. RESULTS: Among respondents with 12-month MDD, 94.9% (s.e. = 0.4) had at least one prior disorder (including previous MDD), and 64.6% (s.e. = 0.9) had at least one prior, non-MDD disorder. Previous non-depressive distress, fear and externalising disorders, but not depressive distress disorders, predicted higher impairment (OR = 1.4-1.6) and suicidality (OR = 1.5-2.5), after adjustment for sociodemographic variables. Further adjustment for MDD characteristics weakened, but did not eliminate, these associations. Associations were largely driven by current comorbidities, but both remitted and current externalising disorders predicted suicidality among respondents with 12-month MDD. CONCLUSIONS: These results illustrate the importance of careful psychiatric history taking regarding current anxiety disorders and lifetime externalising disorders in individuals with MDD.

Perceived helpfulness of treatment for alcohol use disorders: Findings from the World Mental Health Surveys.

AIM: We examined prevalence and factors associated with receiving perceived helpful alcohol use disorder (AUD) treatment, and persistence in help-seeking after earlier unhelpful treatment. METHODS: Data came from 27 community epidemiologic surveys of adults in 24 countries using the World Health Organization World Mental Health surveys (n = 93,843). Participants with a lifetime history of treated AUD were asked if they ever received helpful AUD treatment, and how many professionals they had talked to up to and including the first time they received helpful treatment (or how many ever, if they had not received helpful treatment). RESULTS: 11.8% of respondents with lifetime AUD reported ever obtaining treatment (n = 9378); of these, 44% reported that treatment was helpful. The probability of obtaining helpful treatment from the first professional seen was 21.8%; the conditional probability of subsequent professionals being helpful after earlier unhelpful treatment tended to decrease as more professionals were seen. The cumulative probability of receiving helpful treatment at least once increased from 21.8% after the first professional to 79.7% after the seventh professional seen, following earlier unhelpful treatment. However, the cumulative probability of persisting with up to seven professionals in the face of prior treatments being unhelpful was only 13.2%. CONCLUSION: Fewer than half of people with AUDs who sought treatment found treatment helpful; the most important factor was persistence in seeking further treatment if a previous professional had not helped. Future research should examine how to increase the likelihood that AUD treatment is found to be helpful on any given contact.

Tissue macrophages and interferon-gamma signalling control blood-stage Plasmodium chabaudi infections derived from mosquito-transmitted parasites.

Natural infection with Plasmodium parasites, the causative agents of malaria, occurs via mosquito vectors. However, most of our knowledge of the immune response to the blood stages of Plasmodium is from infections initiated by injection of serially blood-passaged infected red blood cells, resulting in an incomplete life cycle in the mammalian host. Vector transmission of the rodent malaria parasite, Plasmodium chabaudi chabaudi AS has been shown to give rise to a more attenuated blood-stage infection in C57Bl/6J mice, when compared to infections initiated with serially blood-passaged P. chabaudi-infected red blood cells. In mouse models, the host immune response induced by parasites derived from natural mosquito transmission is likely to more closely resemble the immune responses to Plasmodium infections in humans. It is therefore important to determine how the host response differs between the two types of infections. As the spleen is considered to be a major contributor to the protective host response to P. chabaudi, we carried out a comparative transcriptomic analysis of the splenic response to recently mosquito-transmitted and serially blood-passaged parasites in C57Bl/6J mice. The attenuated infection arising from recently mosquito-transmitted parasites is characterised by an earlier and stronger myeloid- and IFNγ-related response. Analyses of spleen lysates from the two infections similarly showed stronger or earlier inflammatory cytokine and chemokine production in the recently mosquito-transmitted blood-stage infections. Furthermore, tissue macrophages, including red pulp macrophages, and IFNγ-signalling in myeloid cells, are required for the early control of P. chabaudi recently mosquito-transmitted parasites, thus contributing to the attenuation of mosquito-transmitted infections. The molecules responsible for this early activation response to recently-transmitted blood-stage parasites in mice would be important to identify, as they may help to elucidate the nature of the initial interactions between blood-stage parasites and the host immune system in naturally transmitted malaria.

Generation and Surgical Analysis of Genetic Mouse Models to Study NF-κB-Driven Pathogenesis of Diffuse Large B Cell Lymphoma.

Enforced activation of NF-κB signaling can be achieved by constitutive NF-κB-inducing kinases, IKK2 and NIK, or via lymphoma-associated mutants of MYD88, CARD11, and CD79B. In order to model Diffuse Large B Cell Lymphoma (DLBCL) in mice, conditional alleles for these proteins are combined with alleles targeting Cre recombinase expression in mature B cells. However, unopposed NF-κB signaling promotes plasmablast differentiation, and as a consequence the model system must be complemented with further mutations that block differentiation, such as Prdm1/BLIMP1 inactivation or overexpression of BCL6. Here, we describe the currently available tools for DLBCL models in mice and their relative advantages and drawbacks. Furthermore, we describe methods to monitor lymphomagenesis, using ultrasound tomography of the spleen, and the technique of partial splenectomy surgery with recovery. These powerful techniques allow paired comparison of individual lymphoma cases before and after interventions, including therapies, and to study the evolution of lymphoma over time. NF-κB activation also promotes widespread nodal involvement with lymphoma and we describe the post-mortem dissection of major nodal groups.

Perceived helpfulness of treatment for specific phobia: Findings from the World Mental Health Surveys.

BACKGROUND: Although randomized trials show that specific phobia treatments can be effective, it is unclear whether patients experience treatment as helpful in clinical practice. We investigated this issue by assessing perceived treatment helpfulness for specific phobia in a cross-national epidemiological survey. METHODS: Cross-sectional population-based WHO World Mental Health (WMH) surveys in 24 countries (n=112,507) assessed lifetime specific phobia. Respondents who met lifetime criteria were asked whether they ever received treatment they considered helpful and the number of professionals seen up to the time of receiving helpful treatment. Discrete-event survival analysis was used to calculate conditional-cumulative probabilities of obtaining helpful treatment across number of professionals seen and of persisting in help-seeking after prior unhelpful treatment. RESULTS: 23.0% of respondents reported receiving helpful treatment from the first professional seen, whereas cumulative probability of receiving helpful treatment was 85.7% after seeing up to 9 professionals. However, only 14.7% of patients persisted in seeing up to 9 professionals, resulting in the proportion of patients ever receiving helpful treatment (47.5%) being much lower than it could have been with persistence in help-seeking. Few predictors were found either of perceived helpfulness or of persistence in help-seeking after earlier unhelpful treatments. LIMITATIONS: Retrospective recall and lack of information about either types of treatments received or objective symptomatic improvements limit results. CONCLUSIONS: Despite these limitations, results suggest that helpfulness of specific phobia treatment could be increased, perhaps substantially, by increasing patient persistence in help-seeking after earlier unhelpful treatments. Improved understanding is needed of barriers to help-seeking persistence.

Towards a Combined Use of Geophysics and Remote Sensing Techniques for the Characterization of a Singular Building: "El Torreón" (the Tower) at Ulaca Oppidum (Solosancho, Ávila, Spain).

This research focuses on the study of the ruins of a large building known as "El Torreón" (the Tower), belonging to the Ulaca oppidum (Solosancho, Province of Ávila, Spain). Different remote sensing and geophysical approaches have been used to fulfil this objective, providing a better understanding of the building's functionality in this town, which belongs to the Late Iron Age (ca. 300-50 BCE). In this sense, the outer limits of the ruins have been identified using photogrammetry and convergent drone flights. An additional drone flight was conducted in the surrounding area to find additional data that could be used for more global interpretations. Magnetometry was used to analyze the underground bedrock structure and ground penetrating radar (GPR) was employed to evaluate the internal layout of the ruins. The combination of these digital methodologies (surface and underground) has provided a new perspective for the improved interpretation of "El Torreón" and its characteristics. Research of this type presents additional guidelines for better understanding of the role of this structure with regards to other buildings in the Ulaca oppidum. The results of these studies will additionally allow archaeologists to better plan future interventions while presenting new data that can be used for the interpretation of this archaeological complex on a larger scale.

Perceived helpfulness of treatment for posttraumatic stress disorder: Findings from the World Mental Health Surveys.

BACKGROUND: Perceived helpfulness of treatment is an important healthcare quality indicator in the era of patient-centered care. We examine probability and predictors of two key components of this indicator for posttraumatic stress disorder (PTSD). METHODS: Data come from World Mental Health surveys in 16 countries. Respondents who ever sought PTSD treatment (n = 779) were asked if treatment was ever helpful and, if so, the number of professionals they had to see to obtain helpful treatment. Patients whose treatment was never helpful were asked how many professionals they saw. Parallel survival models were estimated for obtaining helpful treatment in a specific encounter and persisting in help-seeking after earlier unhelpful encounters. RESULTS: Fifty seven percent of patients eventually received helpful treatment, but survival analysis suggests that it would have been 85.7% if all patients had persisted in help-seeking with up to six professionals after earlier unhelpful treatment. Survival analysis suggests that only 23.6% of patients would persist to that extent. Odds of ever receiving helpful treatment were positively associated with receiving treatment from a mental health professional, short delays in initiating help-seeking after onset, absence of prior comorbid anxiety disorders and childhood adversities, and initiating treatment before 2000. Some of these variables predicted helpfulness of specific treatment encounters and others predicted persistence after earlier unhelpful encounters. CONCLUSIONS: The great majority of patients with PTSD would receive treatment they considered helpful if they persisted in help-seeking after initial unhelpful encounters, but most patients whose initial treatment is unhelpful give up before receiving helpful treatment.