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Mesial temporal lobe epilepsy (mTLE) is the most prevalent type of epilepsy in adults. First and subsequent generations of anti-epileptic therapy regimens fail to decrease seizures in a large number of patients suffering from mTLE, leaving surgical ablation of part of the hippocampus as the only therapeutic option to potentially reach seizure freedom. GluK2 has recently been identified as a promising target for the treatment of mTLE using gene therapy. Here, we engineered an adeno-associated virus serotype 9 vector expressing a cluster of two synthetic microRNAs (miRNAs), expressed from the human synapsin promoter, that target GRIK2 mRNA. Intra-hippocampal delivery of this vector in a mouse model of mTLE significantly reduced GRIK2 expression and daily seizure frequency. This treatment also improved the animals' health, reduced their anxiety, and restored working memory. Focal administration of the vector to the hippocampus of cynomolgus monkeys in GLP toxicology studies led to the selective transduction of hippocampal neurons with little exposure elsewhere in the brain and no transduction outside the central nervous system. Expression of miRNAs in hippocampal neurons resulted in substantially decreased GRIK2 mRNA expression. These data suggest that the intra-hippocampal delivery of a GMP-grade AAV9 encoding a synthetic miRNAs targeting GRIK2 is a promising treatment strategy for mTLE.

Background On 15 March 2019, a white supremacist terrorist attacked two mosques in Christchurch, New Zealand. Fifty-one people were killed and another 40 sustained non-fatal gunshot injuries. Aims To examine the mental health of the Muslim community, and individual and exposure-related factors associated with mental health outcomes. Method This is the baseline analysis of a longitudinal study of adults from the Muslim community interviewed 11–32 months after the shootings. It included a diagnostic interview (MINI), measures of sociodemographic factors, prior mental health, prior traumatic events, exposure in the attacks, discrimination, life stressors, social support and religious coping. Logistic regression models examined associations with mental health outcomes. Results The sample comprised 189 participants (mean age 41 (s.d. = 13); 60% female), and included: bereaved, 17% (n = 32); injured survivors 12% (n = 22); non-injured survivors, 19% (n = 36); family members of survivors, 35% (n = 67); and community members without the above exposures, 39% (n = 74). Overall, 61% had at least one mental disorder since the attacks. Those bereaved (P < 0.01, odds ratio 4.28, 95% CI 1.75–10.49) and survivors, whether injured (P < 0.001, odds ratio 18.08, 95% CI 4.70–69.60) or not (P < 0.01, odds ratio 5.26, 95% CI 1.99–13.89), had greater odds of post-traumatic stress disorder. Those bereaved (P < 0.001, odds ratio 5.79, 95% CI 2.49–13.46) or injured (P = 0.04, odds ratio 4.43, 95% CI 1.07–18.28) had greater odds of depression. Conclusions Despite unique features of this attack on a Muslim population, findings accord with previous studies. They suggest generalisability of psychopathology after terror attacks, and that being bereaved or directly experiencing such events is associated with adverse mental health outcomes. Trial registration number The study is registered on the Australian NZ Clinical Trials Registry (ACTRN12620000909921).

Background: Inequities in the incidence and outcomes of first episode psychosis (FEP) for Indigenous peoples are impacted by multiple institutional systems. This study examines Indigenous experiences of these systems to gain an understanding of how to improve institutional responses to FEP inequity. Methods: Critical race theory informed the methods used. Twenty-three participants participated in four focus group interviews, and thirteen individual interviews, including nine Māori youth and young adults with FEP, ten family members, and four Māori health professionals. Participants were asked about lifetime experiences of institutions (health, social, and criminal-justice). An adapted WHO framework for addressing mental health inequities was used to organize and analyse the first round of structural coding, followed by descriptive and pattern coding. Results: Two themes were identified. The first theme signposted opportunities for institutional intervention. Participants critique being processed quickly through institutions that are driven by socio-political agendas, namely perceived risk, threat or crisis. Subsequently, opportunities for meaningful intervention were missed. The second theme identified scope for family orientated responses across sectors. Participants described short-term social interventions and institutional structures that focused on individuals rather than families, emphasizing the need to broaden cross-sector scope to structural interventions for families. Discussion: The findings highlight institutional responses are focused on organisational drivers and downstream issues, that fail to address the fabric of the family social-environmental conditions that maintain Indigenous exposure to psychosis risk and poor outcomes. A pathway to equity would require a shared framework of social responsibility across sectors, that targets structural factors responsive to Indigenous family needs.

Introduction Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine.Methods and analysis This is a prospectively registered, two-centre, single-blind RCT. We aim to recruit 60 participants with TR-MDD aged between 18 and 65 years. Participants will be randomised to 8 weeks of oral ketamine and BAT, or 8 weeks of oral ketamine alone. Feasibility will be assessed by tracking attendance for ketamine and BAT, acceptability of treatment measures and retention to the study follow-up protocol. The primary efficacy outcome measure is the Montgomery-Asberg Depression Rating Scale (MADRS) measured weekly during treatment and fortnightly during 12 weeks of follow-up. Other outcome measures will assess the tolerability of ketamine and BAT, cognition and activity (using actigraphy). Participants will be categorised as non-responders, responders, remitters and relapsed during follow-up. MADRS scores will be analysed using a linear mixed model. For a definitive follow-up RCT study to be recommended, the recruitment expectations will be met and efficacy outcomes consistent with a >20% reduction in relapse rates favouring the BAT and ketamine arm will be achieved.Ethics and dissemination Ethics approval was granted by the New Zealand Central Health and Disability Ethics Committee (reference: 2023 FULL18176). Study findings will be reported to participants, stakeholder groups, conferences and peer-reviewed publications.Trial registration number UTN: U1111-1294-9310, ACTRN12623000817640p.

Recruiting participants for research from highly traumatised ethnic and faith communities requires a participatory and trauma-informed approach that considers logistic barriers, as well as trauma-related and culture-specific issues. Active community engagement through every stage of the project and employing community members in research roles can help build trust, identify and mitigate concerns early, prevent re-traumatization, and ensure that findings will be of value to the community. Some of these research challenges are discussed in the context of the Christchurch mosque terror attacks. These insights may be helpful for researchers and clinicians working in similarly challenging environments.

Background The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care. Aim To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services. Method We consulted with senior leadership, clinical pharmacy, psychiatrists, nursing, service users and Māori mental health workers on issues relating to ketamine treatment. We prepared treatment guidelines taking the evidence base for ketamine treatment and the consultation into account. Results Ketamine treatment guidance is reported. This offers two treatment pathways, including a test of ketamine responsiveness with intramuscular ketamine and the dominant use of oral ketamine for a 3-month course to maximise the opportunity for the short-term benefits of ketamine to accumulate. Conclusions We have responded to the challenges of translating the evidence base for ketamine treatment into a form suitable for routine care.

BackgroundDepression and anxiety are common and debilitating mental disorders with severe negative repercussions at both individual and societal levels. Although virtual reality (VR) has emerged as a safe and effective tool for the treatment of anxiety disorders, studies of the therapeutic application of VR to treat depression are more limited. ObjectiveThe purpose of this study was to test whether a novel type of individualized VR (iVR) can be used to improve self-compassion and decrease depressive symptoms and to evaluate the usability and acceptability of this approach, as rated by participants. The iVR system was designed and developed based on the feedback obtained from a previous study, with improved appearance and feel of the avatar and enhanced graphical quality. MethodsA total of 36 young adult participants were recruited from a university community social media site. Participants were aware that the study was investigating a treatment for depression but were not recruited based on depression diagnosis. Participants were asked to complete 2 iVR sessions, spaced 2 weeks apart. At baseline and upon completion of each iVR session, participants were asked to complete validated measures of self-compassion and depression. Upon completion of both iVR sessions, additional measures were administered to assess participants’ perceptions about the perceived usability and system acceptability of the iVR approach. ResultsSelf-compassion was assessed at the beginning of session 1 (preintervention baseline) and at the end of session 1 (postintervention assessment). Owing to COVID-19 constraints, 36% (13/36) of the participants were unable to complete the follow-up iVR session. Self-compassion was assessed again for the remaining 64% (23/36) of the participants at the end of session 2 (postintervention assessment). Within-group analyses revealed that self-compassion was significantly increased at the end of both session 1 (P=.01) and session 2 (P=.03) relative to baseline. There was also a nonsignificant trend for depressive symptoms to be low at the end of session 2 relative to baseline. Both quantitative and qualitative participant data supported the iVR approach as being acceptable and usable. ConclusionsAlthough these data must be treated as preliminary owing to the small sample size and potential selection bias, the data provide encouraging initial evidence that iVR might be a useful tool to enhance self-compassion and reduce depressive symptoms, highlighting the need for randomized controlled trials in the future.

Introduction Our previous research has demonstrated significant cognitive effects of earthquake exposure 2–3 years following the Canterbury earthquake sequence of 2011. Such impairment has major implications for a population trying to recover, and to rebuild, a devastated city. This study aims to examine psychological, cognitive and biological factors that may contribute to subjective cognitive difficulties in a large group of individuals exposed to the Canterbury earthquake sequence.Methods and analysis Two-hundred earthquake-exposed participants from an existing large cohort study (Christchurch Health and Development Study, CHDS) will be recruited. Inclusion is based on results of online screening of the CHDS cohort, using the Cognitive Failures Questionnaire. Individuals scoring the highest (n=100) and lowest (n=100), representing the highest and lowest levels of subjective cognitive impairment, are selected. Exclusions are: psychotic/bipolar disorders, serious substance/alcohol dependence, chronic medical conditions, pregnancy and previous serious head injury. Participants will undergo a half-day assessment including clinician-rated interviews, self-report measures, objective and subjective cognitive assessments, blood sample collection and physical measurements. The primary analysis will compare cognitive, psychological and biological measures in ‘high’ and ‘low’ subjective cognitive impairment groups. The study will have power (p

Background Compulsory Community Treatment Orders (CTOs) enable psychiatric medication without the need for consent. Careful scrutiny of outcomes including mortality is required to ensure compulsory treatment is evidence-based and ethical. Aims To report mortality for patients placed on CTOs and analyse data according to CTO status, mortality cause and diagnosis. Method Data for all patients placed under CTOs between 1 January 2009 and 31 December 2018 was provided by the Ministry of Health, New Zealand. Data included diagnostic and demographic information, dates of CTOs, and any dates and causes of death. Deaths were categorised into suicides, accidents and assaults, and medical causes. Mortality data are reported according to CTO status and diagnosis. Results A total of 14 726 patients were placed on CTOs over the study period, during which there were 1328 deaths. The mortality rate was 2.97 on and 2.31 off CTOs (rate ratio 1.29, 95% CI 1.14–1.45; P < 0.01). The mortality rate for accidents and assaults was 0.44 on and 0.25 off CTOs (rate ratio 1.73, 95% CI 1.23–2.42; P < 0.01). The mortality rate for medical causes was 2.33 on and 1.90 off CTOs (rate ratio 1.22, 95% CI 1.07–1.40; P < 0.01). The suicide rate was 0.20 on and 0.15 off of CTOs (rate ratio 1.33, 95% CI 0.81–2.12; P = 0.22). Conclusions Increased care and medication provided during compulsory treatment does not the modify the course of illness sufficiently to reduce mortality during CTOs. Higher mortality rates during CTO periods compared with non-CTO periods may reflect greater unwellness during CTOs.

Abstract Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p

Background Compulsory community treatment orders (CTOs) are controversial because they enforce psychiatric treatment of patients in the community. It is important to know which patients benefit from compulsory treatment to better inform CTO use. Aims To examine the effect of a range of diagnoses on outcomes associated with CTOs to determine whether there are specific outcome signatures for CTOs according to diagnosis. Method New Zealand's Ministry of Health databases provided demographic, service use and medication-dispensing data for all individuals placed on a CTO between 2009 and 2018. We used a hierarchical approach to categorise individuals according to diagnosis. Admission rates, admission days per year, community care and medication dispensing were analysed according to diagnosis and CTO status. Results In total, 14 726 patients were placed on a CTO over the 10-year period between 1 January 2009 and 31 December 2018. For psychotic disorders, CTOs were associated with reduced admission frequency and duration. However, the opposite occurred for dementia disorders, bipolar disorders, major depressive disorder and personality disorders. Higher rates of medications, including depot antipsychotic medications, were dispensed on CTOs for all diagnostic groups. Conclusions CTOs were associated with reduced admission frequency and admission days per year for patients with psychotic disorders, whereas the opposite occurred for other diagnostic groups. Rather than seeking to establish whether CTOs are effective, we suggest that there are specific outcome signatures associated with CTOs for different disorders and knowledge of these can improve understanding and clinical practice in this area.

Cognitive screening tests are culture bound and have been shown to perform differently depending on the culture, even with adequate translation. Khan et al examine in detail ways in which the Montreal Cognitive Assessment (MoCA) has been modified for different languages and cultures and produce a systematic guide for future modifications. However, questions arise regarding the availability of the MoCA. Other important issues in the transcultural use and modification of neuropsychiatric tests include providing a culturally safe context for testing, understanding the cultural context in which screening takes place and assessing other neuropsychiatric conditions, which may manifest differently in different cultural contexts and which affect cognition.

Introduction On 15 March 2019, a white supremacist gunman opened fire in two mosques in Christchurch, New Zealand, during Friday prayers, killing 51 people and injuring 40. The event was witnessed by at least 250 survivors and also live streamed on social media, leading to widespread and repeated exposure within the community. It is expected that survivors, families and community members will be at increased risk of developing mental disorders due to the scale and violence of these attacks.This protocol describes the first phase of a proposed longitudinal study to screen and assess the long-term impacts of the terrorist attack on members of the Christchurch Muslim community, to determine clinical need and facilitate access to appropriate interventions and to gain insights into working with such a traumatised, ethnically diverse population. It has been developed in close collaboration with members of that community.Methods and analysis A mixed-method design is described, combining self-report measures with a clinician-administered diagnostic interview. Participants include Christchurch Muslims aged 18 years and over, with a target sample size of n=200. Analyses will determine prevalence of major mental disorders, while regression analyses will model the relationship between pre-event features, trauma exposure and mental disorders. A small number of participants, stratified by exposure type, will also take part in a qualitative interview in English. All study information and self-report measures are provided in translations based on the ethnolinguistic composition of the group and are available in paper and online versions.Ethics and dissemination Ethical approval was granted by the New Zealand Health and Disability Ethics Committee 19/NTA/147. All participants provide informed consent, either written or online via REDCap software. Findings will be disseminated initially to the impacted community, then by publication in scientific journals, presentations and to government agencies.Trial registration number The study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12620000909921.

BackgroundMental health conditions pose a major challenge to health care providers and society at large. The World Health Organization predicts that by 2030, mental health conditions will be the leading cause of disease burden worldwide. The current need for mental health care is overwhelming. In New Zealand, 1 in 6 adults has been diagnosed with common mental disorders, such as depression and anxiety disorders, according to a national survey. Cognitive behavioral therapy (CBT) has been shown to effectively help patients overcome a wide variety of mental health conditions. Virtual reality exposure therapy (VRET) might be one of the most exciting technologies emerging in the clinical setting for the treatment of anxiety and depression. ObjectiveThis study aims to investigate the virtual reality (VR) technologies currently being used to help support the treatment of depression and anxiety. We also aim to investigate whether and how CBT is included as part of VRET and look at the VR technologies and interventions that have been used in recent studies on depression and anxiety. MethodsWe performed a scoping review. To identify significant studies, we decided to use already aggregated sources from the Google Scholar database. Overall, the goal of our search strategy was to limit the number of initial results related to VR in mental health to only a relevant minimum. ResultsUsing our defined keywords, Google Scholar identified >17,300 articles. After applying all the inclusion and exclusion criteria, we identified a total of 369 articles for further processing. After manual evaluation, 34 articles were shortlisted; of the 34 articles, 9 (26%) reported the use of CBT with VR. All of the articles were published between 2017 and 2021. Out of the 9 studies, CBT was conducted within a VR environment in 5 (56%) studies, whereas in the remaining 4 (44%) studies, CBT was used as an addition to VRET. All 9 studies reported the use of CBT either in vivo or in a virtual environment to be effective in supporting the treatment of anxiety or depression. ConclusionsMost studies demonstrated the use of VR to be effective for supporting the treatment of anxiety or depression in a range of settings and recommended its potential as a tool for use in a clinical environment. Even though standalone headsets are much easier to work with and more suitable for home use, the shift from tethered VR headsets to standalone headsets in the mental health environment was not observed. All studies that looked at the use of CBT either in vivo or in a virtual environment found it to be effective in supporting the treatment of anxiety or depression.

Objectives: Research suggests that patients with co-morbid bipolar disorder (BD) and substance use disorder (SUD) have a poorer illness course and clinical outcome. The evidence is limited as SUD patients are often excluded from BD studies. In particular, evidence regarding long term outcomes from studies using psychotherapies as an adjunctive treatment is limited. We therefore examined data from two studies of Interpersonal Social Rhythm Therapy (IPSRT) for BD to determine whether lifetime or current SUD affected outcomes.Methods: Data were analyzed from two previous clinical trials of IPSRT for BD patients. Change in scores on the Social Adjustment Scale (SAS) from 0 to 78 weeks and cumulative mood scores from 0 to 78 weeks, measured using the Life Interval Follow-Up Evaluation (LIFE), were analyzed.Results: Of 122 patients (non-SUD n = 67, lifetime SUD but no current n = 43, current SUD n = 12), 79 received IPSRT and 43 received a comparison therapy—specialist supportive care—over 18 months. Lifetime SUD had a significant negative effect on change in SAS score but not LIFE score. There was no effect of current SUD on either change in score. Secondary analysis showed no correlation between symptom count and change in SAS total score or LIFE score.Conclusion: Current SUD has no impact on mood or functional outcomes, however, current SUD numbers were small, limiting conclusions. Lifetime SUD appears to be associated with impaired functional outcomes from psychotherapy. There is limited research on co-morbid BD and SUD patients undergoing psychotherapy.

Background Despite evidence of gender differences in bipolar disorder characteristics and comorbidity, there is little research on the differences in treatment and service use between men and women with bipolar disorder. Aims To use routine data to describe specialist mental health service contact for bipolar disorder, including in-patient, community and support service contacts; to compare clinical characteristics and mental health service use between men and women in contact with secondary services for bipolar disorder. Method Cross-sectional analysis of mental health patients with bipolar disorder in New Zealand, based on complete national routine health data. Results A total of 3639 individuals were in contact with specialist mental health services with a current diagnosis of bipolar disorder in 2015. Of these 58% were women and 46% were aged 45 and over. The 1-year prevalence rate of bipolar disorder leading to contact with specialist mental health services was 1.56 (95% CI 1.50–1.63) per 100 000 women and 1.20 (95% CI 1.14–1.26) per 100 000 men. Rates of bipolar disorder leading to service contact were 30% higher in women than men (rate ratio 1.30, 95% CI 1.22–1.39). The majority (68%) had a diagnosis of bipolar I disorder. Women were more likely to receive only out-patient treatment and have comorbid anxiety whereas more men had substance use disorder, were convicted for crimes when unwell, received compulsory treatment orders and received in-patient treatment. Conclusions Although the prevalence of bipolar disorder is equal between men and women in the population, women were more likely to have contact with specialist services for bipolar disorder but had a lower intensity of service interaction.

Background: Treatment of borderline personality disorder (BPD) in publicly funded mental health services generally use approaches based on medical interventions and generic case management. Specific psychological therapies developed for BPD may be more effective but have rarely been evaluated in routine clinical practice.Aim: To examine the effectiveness of Mentalization Based Treatment (MBT) in adults with an established diagnosis of BPD under the care of a publicly funded Mental Health Service (MHS), on rates of non-suicidal self-harm (NSSH) and attempted suicide (SA).Methods: A randomized, controlled trial (RCT) comparing 18 months of MBT with Enhanced Therapeutic Case Management (ETCM), a form of Structured Clinical Case Management (ICTRP: ACTRN12612000951853). Participants were adults recruited from a patient population under the care of a publicly funded mental health service (MHS) with a confirmed diagnosis of BPD. The primary outcome measures were the incidence of non-suicidal self-harm or suicide attempt over 18 months of treatment.Results: 72 participants (71 females, 1 male) were randomized to MBT (n = 38) or ETCM (n = 34). Both groups showed a significant reduction in the overall incident rate of SA and NSSH. Between groups, SA rates were higher in the MBT group and conversely NSSH rates were higher in the ECTM group.Conclusions: The introduction of a structured service that delivered a structured psychotherapy (MBT) and an effective case management approach (ETCM) both resulted in a reduction in SA and NSSH. The differences in improvements found between groups within this study setting will require further research.

Memory impairment is an important side-effect of electroconvulsive therapy (ECT). However, predicting which patients are at increased risk of developing this is difficult. The study by Sigström et al compares patients’ experience of memory difficulties before and after ECT and suggests that patients with negative expectations of ECT's memory effects are more likely to have subjective memory worsening post-ECT. This intriguing finding suggests that clinicians may be able to modify the risk of patients developing subjective memory difficulties post-ECT by providing appropriate information and addressing concerns prior to treatment, during the informed consent process.

The term ‘mood stabiliser’ is ill-defined and lacks clinical utility. We propose a framework to evaluate medications and effectively communicate their mood stabilising properties – their acute and prophylactic efficacy across the domains of mania and depression. The standardised framework provides a common definition to facilitate research and clinical practice.

Abstract Background Patients on extracorporeal membrane oxygenation (ECMO) are often among the most severely ill in the intensive care unit. They are often receiving broad-spectrum antibiotics; they have multiple entry points for pathogens; and their immune system is impaired by blood circuit interaction. These factors are thought to predispose them to fungal infections. We thus aimed to evaluate the prevalence, risk factors, and prognosis of fungal infections in adults on ECMO. Methods We conducted a retrospective cohort study using the Extracorporeal Life Support Organization registry, which compiles data on ECMO use from hundreds of international centers. We included all adult patients from 2006 to 2016 on any mode of ECMO with either a diagnosis of fungal infection or a positive fungal culture. Results Our study comprised 2129 adult patients (10.8%) with fungal colonization or infection. Aspergillus involvement (colonization or infection) was present in 272 patients (1.4%), of whom 35.7% survived to hospital discharge. There were 245 patients (1.2%) with Candida invasive bloodstream infection, with 35.9% survival. Risk factors for Aspergillus involvement included solid organ transplant (OR 1.83; p = 0.008), respiratory support (OR 2.75; p

To investigate climatic, spatial, temporal, and environmental patterns associated with hantavirus pulmonary syndrome (HPS) cases in the Four Corners region, we collected exposure site data for HPS cases that occurred in 1993 to 1995. Cases clustered seasonally and temporally by biome type and geographic location, and exposure sites were most often found in pinyon-juniper woodlands, grasslands, and Great Basin desert scrub lands, at elevations of 1,800 m to 2,500 m. Environmental factors (e.g., the dramatic increase in precipitation associated with the 1992 to 1993 El Niño) may indirectly increase the risk for Sin Nombre virus exposure and therefore may be of value in designing disease prevention campaigns.

Previously, we have shown that a maternal low protein diet, fed exclusively during the preimplantation period of mouse development (Emb-LPD), is sufficient to induce by the blastocyst stage a compensatory growth phenotype in late gestation and postnatally, correlating with increased risk of adult onset cardiovascular disease and behavioural dysfunction. Here, we examine mechanisms of induction of maternal Emb-LPD programming and early compensatory responses by the embryo. Emb-LPD induced changes in maternal serum metabolites at the time of blastocyst formation (E3.5), notably reduced insulin and increased glucose, together with reduced levels of free amino acids (AAs) including branched chain AAs leucine, isoleucine and valine. Emb-LPD also caused reduction in the branched chain AAs within uterine fluid at the blastocyst stage. These maternal changes coincided with an altered content of blastocyst AAs and reduced mTORC1 signalling within blastocysts evident in reduced phosphorylation of effector S6 ribosomal protein and its ratio to total S6 protein but no change in effector 4E-BP1 phosphorylated and total pools. These changes were accompanied by increased proliferation of blastocyst trophectoderm and total cells and subsequent increased spreading of trophoblast cells in blastocyst outgrowths. We propose that induction of metabolic programming following Emb-LPD is achieved through mTORC1signalling which acts as a sensor for preimplantation embryos to detect maternal nutrient levels via branched chain AAs and/or insulin availability. Moreover, this induction step associates with changes in extra-embryonic trophectoderm behaviour occurring as early compensatory responses leading to later nutrient recovery.

Published human papillomavirus (HPV) vaccine trials indicate efficacy is strongest for those naive to the vaccine-types. However, few high-risk young women have been followed and cervical HPV has been the predominant outcome measure.We collected cervical and anal swabs, as well as oral rinse specimens from 645 sexually active inner-city young females attending a large adolescent health-clinic in New York City that offers free care and HPV vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type-specific prevalence of HPV at each anatomic site was compared for individuals by vaccination dose using generalized estimating equation logistic regression models.The majority of subjects reported being of non-Caucasian (92%) and/or Hispanic ethnicity (61%). Median age was 18 years (range:14-20). All had practiced vaginal sex, a third (33%) practiced anal sex, and most (77%) had also engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had received three doses. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in 7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types, the detection of HPV in the cervix of vaccinated compared to unvaccinated adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19, 95%CI:0.06-0.75), HPV16 (OR = 0.31, 95%CI:0.11-0.88) and HPV18 (OR = 0.14, 95%CI:0.03-0.75). For anal HPV, the risk of detecting vaccine types HPV6/11 (OR = 0.27, 95%CI:0.10-0.72) and HPV18(OR = 0.12, 95%CI:0.01-1.16) were significantly reduced for vaccinated adolescents however, the risk for HPV16 was not significantly decreased (OR = 0.63, 95%CI:0.18-2.20).HPV Prevalence is extremely high in inner-city female adolescents. Administration of the HPV vaccine reduced the risk for cervical HPV; however continued follow-up is required to assess the protection for HPV at all sites in young women with high exposure.

Advocacy is a crucial activity for achieving the goals of VISION 2020: The Right to Sight. Progress towards the elimination of avoidable blindness depends on political will and on making available more human and financial resources. In order for this to happen, advocacy is necessary: it can influence the policies and practices of key decision makers, particularly governments, the Word Health Organization (WHO), and development and funding bodies.