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At the turn of the nineteenth century the numerous small municipalities of the Cape Peninsula were clearly in need of reorganisation. For this reason the Cape Peninsula Commission of 1902 was instituted to investigate the position and make recommendations for improvement. The majority report urged the amalgamation of most of the towns into a single body, while the minority report suggested two smaller corporations. Neither recommendation was adopted, however, for despite their dependence on one another for basic utilities the municipalities clung fiercely to their autonomy and resisted any change.

Objective There is a lack of UK guidance regarding routine use of probiotics in preterm infants to prevent necrotising enterocolitis, late-onset sepsis and death. As practices can vary, we aimed to determine the current usage of probiotics within neonatal units in the UK.Design and setting Using NeoTRIPS, a trainee-led neonatal research network, an online survey was disseminated to neonatal units of all service levels within England, Scotland, Northern Ireland and Wales in 2022. Trainees were requested to complete one survey per unit regarding routine probiotic administration.Results 161 of 188 (86%) neonatal units responded to the survey. 70 of 161 (44%) respondents routinely give probiotics to preterm infants. 45 of 70 (64%) use the probiotic product Lactobacillus acidophilus NCFM/Bifidobacterium bifidum Bb-06/B. infantis Bi-26 (Labinic™). 57 of 70 (81%) start probiotics in infants ≤32 weeks’ gestation. 33 of 70 (47%) had microbiology departments that were aware of the use of probiotics and 64 of 70 (91%) had a guideline available. Commencing enteral feeds was a prerequisite to starting probiotics in 62 of 70 (89%) units. The majority would stop probiotics if enteral feeds were withheld (59 of 70; 84%) or if the infant was being treated for necrotising enterocolitis (69 of 70; 99%). 24 of 91 (26%) units that did not use probiotics at the time of the survey were planning to introduce them within the next 12 months.Conclusions More than 40% of all UK neonatal units that responded are now routinely administering probiotics, with variability in the product used. With increased probiotic usage in recent years, there is a need to establish whether this translates to improved clinical outcomes.

This paper presents an overview of the functionalities and applications of Exasim, an open-source code for generating high-order discontinuous Galerkin codes to numerically solve parametrized partial differential equations (PDEs). The software combines high-level and low-level languages to construct parametrized PDE models via Julia, Python or Matlab scripts and produce high-performance C++ codes for solving the PDE models on CPU and Nvidia GPU processors with distributed memory. Exasim provides matrix-free discontinuous Galerkin discretization schemes together with scalable reduced basis preconditioners and Newton-GMRES solvers, making it suitable for accurate and efficient approximation of wide-ranging classes of PDEs.

Abstract Background The disproportionately high burden of mental disorders in low- and middle-income countries, coupled with the overwhelming lack of resources, requires an innovative approach to intervention and response. This study evaluated the feasibility of delivering a maternal mental health service in a severely-resource constrained setting as part of routine service delivery. Methods This exploratory feasibility study was undertaken at two health facilities in Afghanistan that did not have specialist mental health workers. Women who had given birth in the past 12 months were screened for depressive symptoms with the PHQ9 and invited to participate in a psychological intervention which was offered through an infant feeding scheme. Results Of the 215 women screened, 131 (60.9%) met the PHQ9 criteria for referral to the intervention. The screening prevalence of postnatal depression was 61%, using a PHQ9 cut-off score of 12. Additionally, 29% of women registered as suicidal on the PHQ9. Several demographic and psychosocial variables were associated with depressive symptoms in this sample, including nutritional status of the infant, anxiety symptoms, vegetative and mood symptoms, marital difficulties, intimate partner violence, social isolation, acute stress and experience of trauma. Of the 47 (65%) women who attended all six sessions of the intervention, all had significantly decreased PHQ9 scores post-intervention. Conclusion In poorly resourced environments, where the prevalence of postnatal depression is high, a shift in response from specialist-based to primary health care-level intervention may be a viable way to provide maternal mental health care. It is recommended that such programmes also consider home-visiting components and be integrated into existing infant and child health programmes. Manualised, evidence-based psychological interventions, delivered by non-specialist health workers, can improve outcomes where resources are scarce.

Classical aniridia is a congenital and progressive panocular disorder almost exclusively caused by heterozygous loss-of-function variants at the PAX6 locus. We report nine individuals from five families with severe aniridia and/or microphthalmia (with no detectable PAX6 mutation) with ultrarare monoallelic missense variants altering the Arg51 codon of MAB21L1. These mutations occurred de novo in 3/5 families, with the remaining families being compatible with autosomal dominant inheritance. Mice engineered to carry the p.Arg51Leu change showed a highly-penetrant optic disc anomaly in heterozygous animals with severe microphthalmia in homozygotes. Substitutions of the same codon (Arg51) in MAB21L2, a close homolog of MAB21L1, cause severe ocular and skeletal malformations in humans and mice. The predicted nucleotidyltransferase function of MAB21L1 could not be demonstrated using purified protein with a variety of nucleotide substrates and oligonucleotide activators. Induced expression of GFP-tagged wildtype and mutant MAB21L1 in human cells caused only modest transcriptional changes. Mass spectrometry of immunoprecipitated protein revealed that both mutant and wildtype MAB21L1 associate with transcription factors that are known regulators of PAX6 (MEIS1, MEIS2 and PBX1) and with poly(A) RNA binding proteins. Arg51 substitutions reduce the association of wild-type MAB21L1 with TBL1XR1, a component of the NCoR complex. We found limited evidence for mutation-specific interactions with MSI2/Musashi-2, an RNA-binding proteins with effects on many different developmental pathways. Given that biallelic loss-of-function variants in MAB21L1 result in a milder eye phenotype we suggest that Arg51-altering monoallelic variants most plausibly perturb eye development via a gain-of-function mechanism.

Identifying causative variants in cis-regulatory elements (CRE) in neurodevelopmental disorders has proven challenging. We have used in vivo functional analyses to categorize rigorously filtered CRE variants in a clinical cohort that is plausibly enriched for causative CRE mutations: 48 unrelated males with a family history consistent with X-linked intellectual disability (XLID) in whom no detectable cause could be identified in the coding regions of the X chromosome (chrX). Targeted sequencing of all chrX CRE identified six rare variants in five affected individuals that altered conserved bases in CRE targeting known XLID genes and segregated appropriately in families. Two of these variants, FMR1CRE and TENM1CRE, showed consistent site- and stage-specific differences of enhancer function in the developing zebrafish brain using dual-color fluorescent reporter assay. Mouse models were created for both variants. In male mice Fmr1CRE induced alterations in neurodevelopmental Fmr1 expression, olfactory behavior and neurophysiological indicators of FMRP function. The absence of another likely causative variant on whole genome sequencing further supported FMR1CRE as the likely basis of the XLID in this family. Tenm1CRE mice showed no phenotypic anomalies. Following the release of gnomAD 2.1, reanalysis showed that TENM1CRE exceeded the maximum plausible population frequency of a XLID causative allele. Assigning causative status to any ultra-rare CRE variant remains problematic and requires disease-relevant in vivo functional data from multiple sources. The sequential and bespoke nature of such analyses renders them time-consuming and challenging to scale for routine clinical use.

Abstract Background Rates of violence against women are reported to be highest in Africa compared to other continents. We aimed to determine associations between mental illness, demographic, psychosocial and economic factors with experience of intimate partner violence (IPV) among pregnant women in a low resource setting in Cape Town and to explore the contextual elements pertaining to domestic violence. Methods We recruited adult women attending antenatal services at a primary-level maternity facility. Demographic, socioeconomic and psychosocial data were collected by questionnaire. The Expanded Mini- International Neuropsychiatric Interview (MINI) Version 5.0.0 was used to assess mental health status and the Revised Conflict Tactic Scale (CTS2) used to assess IPV in the six months prior to the study. Non-parametric tests, Wilcoxon sum of rank test, Fisher Exact and two sample T test and multicollinearity tests were performed. Descriptive, bivariate and logistic regression analyses were conducted to identify associations between the outcome of interest and key predictors. A probability value of p ≤ 0.05 was selected. From counselling case notes, a thematic content analysis was conducted to describe contextual factors pertaining to forms of domestic violence (DV). Results The prevalence of IPV was 15% of a sample of 376 women. Women who were food insecure, unemployed, in stable but unmarried relationships, had experienced any form of past abuse and were not pleased about the current pregnancy were more likely to experience IPV. MINI-defined mental health problems and a history of mental illness were significantly associated with IPV. Qualitative analysis of 95 counselling case notes revealed that DV within the household was not limited to intimate partners and, DV in this context was often perceived as ‘normal’ behaviour by the participants. Conclusions This study contributes towards a greater understanding of the risk profile for IPV amongst pregnant women in low-income settings. Adversity, including food insecurity and mental ill-health are closely associated with IPV during the antenatal period. Advocates against violence against pregnant women are advised to consider that violence in the home may be perpetrated by non-intimate partners and may by enabled by a pervasive belief in the acceptability of the violence.

Abstract Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development.

Purpose.The burden of common perinatal mental disorders (CPMD) in low-and-middle-income countries is substantially higher than high-income countries, with low levels of detection, service provision and treatment in resource-constrained settings. We describe the development of an ultra-short screening tool to detect antenatal depression, anxiety disorders and maternal suicidal ideation.Methods.A sample of 376 women was recruited at a primary-level obstetric clinic. Five depression and anxiety symptom-screening questionnaires, demographics and psychosocial risk questionnaires were administered. All participants were assessed with the Mini-International Neuropsychiatric Interview (MINI), a structured, diagnostic interview. Screening tool items were analysed against diagnostic data using multiple logistic regression and receiver operating curve (ROC) analysis.Results.The prevalence of MINI-defined major depressive episode (MDE) and/or anxiety disorders was 33%. Overall, 18% of participants expressed suicidal ideation and behaviour, 54% of these had no depression or anxiety diagnosis. Multiple logistic regression identified four screening items that were independently predictive of MDE and anxiety disorders, investigating depressed mood, anhedonia, anxiety symptoms and suicidal ideation. ROC analysis of these combined items yielded an area under the curve of 0.83 (95% CI 0.78–0.88). A cut-off score of 2 or more offered a sensitivity of 78% and specificity of 82%.Conclusion.This novel screening tool is the first measure of CPMD developed in South Africa to include depressed mood, anxiety symptoms and suicidal ideation. While the tool requires further investigation, it may be useful for the early identification of mental health symptoms and morbidity in the perinatal period.

An amendment to this paper has been published and can be accessed via the original article.

Antenatal depression and anxiety disorders are highly prevalent in low and middle-income countries. Screening of pregnant women in primary care antenatal settings provides an opportunity for entry to care, but data are needed on the performance of different screening tools. We compared five widely-used questionnaires in a sample of pregnant women in urban South Africa.Pregnant women attending a primary care antenatal clinic were administered five tools by trained research assistants: the Edinburgh Postnatal Depression Scale (EPDS), the Patient Health Questionnaire (PHQ-9), the Kessler Psychological Distress scale (K10) and a shortened 6-item version (K6), the Whooley questions and the two-item Generalised Anxiety Disorder scale (GAD-2). Following this, a registered mental health counsellor administered the MINI Plus, a structured clinical diagnostic interview. The Area Under the Curve (AUC) from Receiver Operator Characteristic curve analysis was used to summarise screening test performance and Cronbach's α used to assess internal consistency.Of 376 participants, 32% were diagnosed with either MDE and/or anxiety disorders. All five questionnaires demonstrated moderate to high performance (AUC = 0.78-0.85). The EPDS was the best performing instrument for detecting MDE and the K10 and K6 for anxiety disorder. For MDE and/or anxiety disorders, the EPDS had the highest AUC (0.83). Of the short instruments, the K10 (AUC = 0.85) and the K6 (AUC = 0.85) performed the best, with the K6 showing good balance between sensitivity (74%) and specificity (85%) and a good positive predictive value (70%). The Whooley questions (AUC = 0.81) were the best performing ultra-short instrument. Internal consistency ranged from good to acceptable (α = 0.89-0.71). However, the PPV of the questionnaires compared with the diagnostic interview, ranged from 54% to 71% at the optimal cut-off scores.Universal screening for case identification of antenatal depression and anxiety disorders in low-resource settings can be conducted with a number of commonly used screening instruments. Short and ultra-short screening instruments such as the K6 and the Whooley questions may be feasible and acceptable for use in these settings.

We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3' (telomeric) to PAX6 and one within a gene desert 5' (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS which lies close to the Xp breakpoint. Disruption of PHF21A has previously been implicated in the causation of intellectual disability (but not aniridia). Plausibly causative mutations were identified in 15 out of 42 individuals (12/32 aniridia; 3/11 Gillespie syndrome). Fourteen of these mutations presented in the known aniridia genes; PAX6, FOXC1 and PITX2. The large number of individuals in the cohort with no mutation identified suggests greater locus heterogeneity may exist in both isolated and syndromic aniridia than was previously appreciated.

Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function.

The zebrafish epithalamus is part of the diencephalon and encompasses three major components: the pineal, the parapineal and the habenular nuclei. Using sox2 knockdown, we show here that this key transcriptional regulator has pleiotropic effects during the development of these structures. Sox2 negatively regulates pineal neurogenesis. Also, Sox2 is identified as the unknown factor responsible for pineal photoreceptor prepatterning and performs this function independently of the BMP signaling. The correct levels of sox2 are critical for the functionally important asymmetrical positioning of the parapineal organ and for the migration of parapineal cells as a coherent structure. Deviations from this strict control result in defects associated with abnormal habenular laterality, which we have documented and quantified in sox2 morphants.

No abstract available.

The transcription factor Pax6 is a developmental regulator with a crucial role in development of the eye, brain, and olfactory system. Pax6 is also required for correct development of the endocrine pancreas and specification of hormone producing endocrine cell types. Glucagon-producing cells are almost completely lost in Pax6-null embryos, and insulin-expressing beta and somatostatin-expressing delta cells are reduced. While the developmental role of Pax6 is well-established, investigation of a further role for Pax6 in the maintenance of adult pancreatic function is normally precluded due to neonatal lethality of Pax6-null mice. Here a tamoxifen-inducible ubiquitous Cre transgene was used to inactivate Pax6 at 6 months of age in a conditional mouse model to assess the effect of losing Pax6 function in adulthood. The effect on glucose homeostasis and the expression of key islet cell markers was measured. Homozygous Pax6 deletion mice, but not controls, presented with all the symptoms of classical diabetes leading to severe weight loss requiring termination of the experiment five weeks after first tamoxifen administration. Immunohistochemical analysis of the pancreata revealed almost complete loss of Pax6 and much reduced expression of insulin, glucagon, and somatostatin. Several other markers of islet cell function were also affected. Notably, strong upregulation in the number of ghrelin-expressing endocrine cells was observed. These findings demonstrate that Pax6 is essential for adult maintenance of glucose homeostasis and function of the endocrine pancreas.

Pax6 is a developmental control gene essential for eye development throughout the animal kingdom. In addition, Pax6 plays key roles in other parts of the CNS, olfactory system, and pancreas. In mammals a single Pax6 gene encoding multiple isoforms delivers these pleiotropic functions. Here we provide evidence that the genomes of many other vertebrate species contain multiple Pax6 loci. We sequenced Pax6-containing BACs from the cartilaginous elephant shark (Callorhinchus milii) and found two distinct Pax6 loci. Pax6.1 is highly similar to mammalian Pax6, while Pax6.2 encodes a paired-less Pax6. Using synteny relationships, we identify homologs of this novel paired-less Pax6.2 gene in lizard and in frog, as well as in zebrafish and in other teleosts. In zebrafish two full-length Pax6 duplicates were known previously, originating from the fish-specific genome duplication (FSGD) and expressed in divergent patterns due to paralog-specific loss of cis-elements. We show that teleosts other than zebrafish also maintain duplicate full-length Pax6 loci, but differences in gene and regulatory domain structure suggest that these Pax6 paralogs originate from a more ancient duplication event and are hence renamed as Pax6.3. Sequence comparisons between mammalian and elephant shark Pax6.1 loci highlight the presence of short- and long-range conserved noncoding elements (CNEs). Functional analysis demonstrates the ancient role of long-range enhancers for Pax6 transcription. We show that the paired-less Pax6.2 ortholog in zebrafish is expressed specifically in the developing retina. Transgenic analysis of elephant shark and zebrafish Pax6.2 CNEs with homology to the mouse NRE/Pα internal promoter revealed highly specific retinal expression. Finally, morpholino depletion of zebrafish Pax6.2 resulted in a "small eye" phenotype, supporting a role in retinal development. In summary, our study reveals that the pleiotropic functions of Pax6 in vertebrates are served by a divergent family of Pax6 genes, forged by ancient duplication events and by independent, lineage-specific gene losses.

As one article in a series on Global Mental Health Practice, Simone Honikman and colleagues from South Africa provide a case study of the Perinatal Mental Health Project, which delivered mental health care to pregnant women in a collaborative, step-wise manner, making use of existing resources in primary care.

The PAX6 gene plays a crucial role in development of the eye, brain, olfactory system and endocrine pancreas. Consistent with its pleiotropic role the gene exhibits a complex developmental expression pattern which is subject to strict spatial, temporal and quantitative regulation. Control of expression depends on a large array of cis-elements residing in an extended genomic domain around the coding region of the gene. The minimal essential region required for proper regulation of this complex locus has been defined through analysis of human aniridia-associated breakpoints and YAC transgenic rescue studies of the mouse smalleye mutant. We have carried out a systematic DNase I hypersensitive site (HS) analysis across 200 kb of this critical region of mouse chromosome 2E3 to identify putative regulatory elements. Mapping the identified HSs onto a percent identity plot (PIP) shows many HSs correspond to recognisable genomic features such as evolutionarily conserved sequences, CpG islands and retrotransposon derived repeats. We then focussed on a region previously shown to contain essential long range cis-regulatory information, the Pax6 downstream regulatory region (DRR), allowing comparison of mouse HS data with previous human HS data for this region. Reporter transgenic mice for two of the HS sites, HS5 and HS6, show that they function as tissue specific regulatory elements. In addition we have characterised enhancer activity of an ultra-conserved cis-regulatory region located near Pax6, termed E60. All three cis-elements exhibit multiple spatio-temporal activities in the embryo that overlap between themselves and other elements in the locus. Using a deletion set of YAC reporter transgenic mice we demonstrate functional interdependence of the elements. Finally, we use the HS6 enhancer as a marker for the migration of precerebellar neuro-epithelium cells to the hindbrain precerebellar nuclei along the posterior and anterior extramural streams allowing visualisation of migratory defects in both pathways in Pax6(Sey/Sey) mice.

List of abstracts and authors: 1. Antipsychotics in anxiety disorders Christer Allgulander 2. Anxiety in somatic disorders Christer Allgulander 3. Community rehabilitation of the schizophrenic patient Orlando Alonso Betancourt, Maricela Morales Herrera 4. Dual diagnosis: A theory-driven multidisciplinary approach for integrative care David Blackbeard 5. The emotional language of the gut - when 'psyche' meets 'soma' Helen Clark 6. The Psychotherapy of bipolar disorder Franco Colin 7. The Psychotherapy of bipolar disorder Franco Colin 8. Developing and adopting mental health policies and plans in Africa: Lessons from South Africa, Uganda and Zambia Sara Cooper, Sharon Kleintjes, Cynthia Isaacs, Fred Kigozi, Sheila Ndyanabangi, Augustus Kapungwe, John Mayeya, Michelle Funk, Natalie Drew, Crick Lund 9. The importance of relapse prevention in schizophrenia Robin Emsley 10. Mental Health care act: Fact or fiction? Helmut Erlacher, M Nagdee 11. Does a dedicated 72-hour observation facility in a district hospital reduce the need for involuntary admissions to a psychiatric hospital? Lennart Eriksson 12. The incidence and risk factors for dementia in the Ibadan study of ageing Oye Gureje, Lola Kola, Adesola Ogunniyi, Taiwo Abiona 13. Is depression a disease of inflammation? Angelos Halaris 14. Paediatric bipolar disorder: More heat than light? Sue Hawkridge 15. EBM: Anova Conundrum Elizabeth L (Hoepie) Howell 16. Tracking the legal status of a cohort of inpatients on discharge from a 72-hour assessment unit Bernard Janse van Rensburg 17. Dual diagnosis units in psychiatric facilities: Opportunities and challenges Yasmien Jeenah 18. Alcohol-induced psychotic disorder: A comparative study on the clinical characteristics of patients with alcohol dependence and schizophrenia Gerhard Jordaan, D G Nel, R Hewlett, R Emsley 19. Anxiety disorders: the first evidence for a role in preventive psychiatry Andre F Joubert 20. The end of risk assessment and the beginning of start Sean Kaliski 21. Psychiatric disorders abd psychosocial correlates of high HIV risk sexual behaviour in war-effected Eatern Uganda E Kinyada, H A Weiss, M Mungherera, P Onyango Mangen, E Ngabirano, R Kajungu, J Kagugube, W Muhwezi, J Muron, V Patel 22. One year of Forensic Psychiatric assessment in the Northern Cape: A comparison with an established assessment service in the Eastern Cape N K Kirimi, C Visser 23. Mental Health service user priorities for service delivery in South Africa Sharon Kleintjes, Crick Lund, Leslie Swartz, Alan Flisher and MHaPP Research Programme Consortium 24. The nature and extent of over-the-counter and prescription drug abuse in cape town Liezl Kramer 25. Physical health issues in long-term psychiatric inpatients: An audit of nursing statistics and clinical files at Weskoppies Hospital Christa Kruger 26. Suicide risk in Schizophrenia - 20 Years later, a cohort study Gian Lippi, Ean Smit, Joyce Jordaan, Louw Roos 27.Developing mental health information systems in South Africa: Lessons from pilot projects in Northern Cape and KwaZulu-Natal Crick Lund, S Skeen, N Mapena, C Isaacs, T Mirozev and the Mental Health and Poverty Research Programme Consortium Institution 28. Mental health aspects of South African emigration Maria Marchetti-Mercer 29. What services SADAG can offer your patients Elizabeth Matare 30. Culture and language in psychiatry Dan Mkize 31. Latest psychotic episode Povl Munk-Jorgensen 32. The Forensic profile of female offenders Mo Nagdee, Helmut Fletcher 33. The intra-personal emotional impact of practising psychiatry Margaret Nair 34. Highly sensitive persons (HSPs) and implications for treatment Margaret Nair 35. Task shifting in mental health - The Kenyan experience David M Ndetei 36. Bridging the gap between traditional healers and mental health in todya's modern psychiatry David M Ndetei 37. Integrating to achieve modern psychiatry David M Ndetei 38. Non-medical prescribing: Outcomes from a pharmacist-led post-traumatic stress disorder clinic A Parkinson 39. Is there a causal relationship between alcohol and HIV? Implications for policy, practice and future research Charles Parry 40. Global mental health - A new global health discipline comes of age Vikram Patel 41. Integrating mental health into primary health care: Lessons from pilot District demonstration sites in Uganda and South Africa Inge Petersen, Arvin Bhana, K Baillie and MhaPP Research Programme Consortium 42. Personality disorders -The orphan child in axis I - Axis II Dichotomy Willie Pienaar 43. Case Studies in Psychiatric Ethics Willie Pienaar 44. Coronary artery disease and depression: Insights into pathogenesis and clinical implications Janus Pretorius 45. Impact of the Mental Health Care Act No. 17 of 2002 on designated hospitals in KwaZulu-Natal: Triumphs and trials Suvira Ramlall, Jennifer Chipps 46. Biological basis of addication Solomon Rataemane 47. Genetics of Schizophrenia Louw Roos 48. Management of delirium - Recent advances Shaquir Salduker 49. Social neuroscience: Brain research on social issues Manfred Spitzer 50. Experiments on the unconscious Manfred Spitzer 51. The Psychology and neuroscience of music Manfred Spitzer 52. Mental disorders in DSM-V Dan Stein 53. Personality, trauma exposure, PTSD and depression in a cohort of SA Metro policemen: A longitudinal study Ugashvaree Subramaney 54. Eating disorders: An African perspective Christopher Szabo 55. An evaluation of the WHO African Regional strategy for mental health 2001-2010 Thandi van Heyningen, M Majavu, C Lund 56. A unitary model for the motor origin of bipolar mood disorders and schizophrenia Jacques J M van Hoof 57. The origin of mentalisation and the treatment of personality disorders Jacques J M Hoof 58. How to account practically for 'The Cause' in psychiatric diagnostic classification C W (Werdie) van Staden POSTER PRESENTATIONS 59. Problem drinking and physical and sexual abuse at WSU Faculty of Health Sciences, Mthatha, 2009 Orlando Alonso Betancourt, Maricela Morales Herrera, E, N Kwizera, J L Bernal Munoz 60. Prevalence of alcohol drinking problems and other substances at WSU Faculty of Health Sciences, Mthatha, 2009 Orlando Alonso Betancourt, Maricela Morales Herrera, E, N Kwizera, J L Bernal Munoz 61. Lessons learnt from a modified assertive community-based treatment programme in a developing country Ulla Botha, Liezl Koen, John Joska, Linda Hering, Piet Ooosthuizen 62. Perceptions of psychologists regarding the use of religion and spirituality in therapy Ottilia Brown, Diane Elkonin 63. Resilience in families where a member is living with schizophreni Ottilia Brown, Jason Haddad, Greg Howcroft 64. Fusion and grandiosity - The mastersonian approach to the narcissistic disorder of the self William Griffiths, D Macklin, Loray Daws 65. Not being allowed to exist - The mastersonian approach to the Schizoid disorder of the self William Griffiths, D Macklin, Loray Daws 66. Risky drug-injecting behaviours in Cape Town and the need for a needle exchange programme Volker Hitzeroth 67. Neuroleptic malignant syndrome in adolescents in the Western Cape: A case series Terri Henderson 68. Experience and view of local academic psychiatrists on the role of spirituality in South African specialist psychiatry, compared with a qualitative analysis of the medical literature Bernard Janse van Rensburg 69. The role of defined spirituality in local specialist psychiatric practice and training: A model and operational guidelines for South African clinical care scenarios Bernard Janse van Rensburg 70. Handedness in schizophrenia and schizoaffective disorder in an Afrikaner founder population Marinda Joubert, J L Roos, J Jordaan 71. A role for structural equation modelling in subtyping schizophrenia in an African population Liezl Koen, Dana Niehaus, Esme Jordaan, Robin Emsley 72. Caregivers of disabled elderly persons in Nigeria Lola Kola, Oye Gureje, Adesola Ogunniyi, Dapo Olley 73. HIV Seropositivity in recently admitted and long-term psychiatric inpatients: Prevalence and diagnostic profile Christina Kruger, M P Henning, L Fletcher 74. Syphilis seropisitivity in recently admitted longterm psychiatry inpatients: Prevalence and diagnostic profile Christina Kruger, M P Henning, L Fletcher 75. 'The Great Suppression' Sarah Lamont, Joel Shapiro, Thandi Groves, Lindsey Bowes 76. Not being allowed to grow up - The Mastersonian approach to the borderline personality Daleen Macklin, W Griffiths 77. Exploring the internal confirguration of the cycloid personality: A Rorschach comprehensive system study Daleen Macklin, Loray Daws, M Aronstam 78. A survey to determine the level of HIV related knowledge among adult psychiatric patients admitted to Weskoppies Hospital T G Magagula, M M Mamabolo, C Kruger, L Fletcher 79. A survey of risk behaviour for contracting HIV among adult psychiatric patients admitted to Weskoppies Hospital M M Mamabolo, T G Magagula, C Kruger, L Fletcher 80. A retrospective review of state sector outpatients (Tara Hospital) prescribed Olanzapine: Adherence to metabolic and cardiovascular screening and monitoring guidelines Carina Marsay, C P Szabo 81. Reported rapes at a hospital rape centre: Demographic and clinical profiles Lindi Martin, Kees Lammers, Donavan Andrews, Soraya Seedat 82. Exit examination in Final-Year medical students: Measurement validity of oral examinations in psychiatry Mpogisheng Mashile, D J H Niehaus, L Koen, E Jordaan 83. Trends of suicide in the Transkei region of South Africa Banwari Meel 84. Functional neuro-imaging in survivors of torture Thriya Ramasar, U Subramaney, M D T H W Vangu, N S Perumal 85. Newly diagnosed HIV+ in South Africa: Do men and women enroll in care? Dinesh Singh, S Hoffman, E A Kelvin, K Blanchard, N Lince, J E Mantell, G Ramjee, T M Exner 86. Diagnostic utitlity of the International HIC Dementia scale for Asymptomatic HIV-Associated neurocognitive impairment and HIV-Associated neurocognitive disorder in South Africa Dinesh Singh, K Goodkin, D J Hardy, E Lopez, G Morales 87. The Psychological sequelae of first trimester termination of pregnancy (TOP): The impact of resilience Ugashvaree Subramaney 88. Drugs and other therapies under investigation for PTSD: An international database Sharain Suliman, Soraya Seedat 89. Frequency and correlates of HIV Testing in patients with severe mental illness Hendrik Temmingh, Leanne Parasram, John Joska, Tania Timmermans, Pete Milligan, Helen van der Plas, Henk Temmingh 90. A proposed mental health service and personnel organogram for the Elizabeth Donkin psychiatric Hospital Stephan van Wyk, Zukiswa Zingela 91. A brief report on the current state of mental health care services in the Eastern Cape Stephan van Wyk, Zukiswa Zingela, Kiran Sukeri, Heloise Uys, Mo Nagdee, Maricela Morales, Helmut Erlacher, Orlando Alonso 92. An integrated mental health care service model for the Nelson Mandela Bay Metro Stephan van Wyk, Zukiswa Zingela, Kiran Sukeri 93. Traditional and alternative healers: Prevalence of use in psychiatric patients Zukiswa Zingela, S van Wyk, W Esterhuysen, E Carr, L Gaauche

While not denying the tragedy of the high mortality of people in the concentration camps in the South African War of 1899 - 1902, this article suggests that, for Lord Milner and the British Colonial Office, the camps became a means of introducing the rural society of the Boers to the facilities of modern life. To some extent they became, in effect, part of Milner's project for 'civilising' and assimilating the Boers into British colonial society. The high mortality rate was finally contained through the introduction of a modern public health system, including the use of statistics and the employment of qualified doctors and nurses. Young Boer women working in the camp hospitals as nurse aids were trained as 'probationers' and classes in infant and child care were offered to the Boer mothers. In addition, the need for adequate water supplies and effective sanitation meant that an infrastructure was established in the camps that familiarised the Boers with modern sanitary routines and left a legacy of more substantial services for the Transvaal and Orange Free State villages. Author comment: My article was never intended to denigrate Afrikaners in any way. The republican Boers were caught up in an unjust war and they suffered dreadful losses as a result. However, I have argued elsewhere that many of the farm families, who had had little contact with modern preventive medicine, functioned within a different cultural world from the British who ran the camps. I have discussed this in much more detail in the following article: Van Heyningen E. Women and disease. The clash of medical cultures in the concentration camps of the South African War. In: Cuthbertson G, Grundlingh A, Suttie M-L, editors. Writing a wider war. Rethinking gender, race, and identity in the South African War, 1899 - 1902. Athens: Ohio University Press, 2002; p. 186 - 212. A shorter version of the article has also been published in Van Heyningen E. British doctors versus Boer women: Clash of medical cultures. In: Pretorius F, editor. Scorched Earth. Cape Town: Human & Rousseau, 2001; p. 78 - 197. There is also an Afrikaans version of this book published under the title of Verskroeide aarde. The same ideas are discussed by Professor Pretorius and myself in the documentary Scorched Earth which has been aired several times recently on the History Channel of DSTV.

Neural stem cell self-renewal, neurogenesis, and cell fate determination are processes that control the generation of specific classes of neurons at the correct place and time. The transcription factor Pax6 is essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system, including the cerebral cortex. We used Pax6 as an entry point to define the cellular networks controlling neural stem cell self-renewal and neurogenesis in stem cells of the developing mouse cerebral cortex. We identified the genomic binding locations of Pax6 in neocortical stem cells during normal development and ascertained the functional significance of genes that we found to be regulated by Pax6, finding that Pax6 positively and directly regulates cohorts of genes that promote neural stem cell self-renewal, basal progenitor cell genesis, and neurogenesis. Notably, we defined a core network regulating neocortical stem cell decision-making in which Pax6 interacts with three other regulators of neurogenesis, Neurog2, Ascl1, and Hes1. Analyses of the biological function of Pax6 in neural stem cells through phenotypic analyses of Pax6 gain- and loss-of-function mutant cortices demonstrated that the Pax6-regulated networks operating in neural stem cells are highly dosage sensitive. Increasing Pax6 levels drives the system towards neurogenesis and basal progenitor cell genesis by increasing expression of a cohort of basal progenitor cell determinants, including the key transcription factor Eomes/Tbr2, and thus towards neurogenesis at the expense of self-renewal. Removing Pax6 reduces cortical stem cell self-renewal by decreasing expression of key cell cycle regulators, resulting in excess early neurogenesis. We find that the relative levels of Pax6, Hes1, and Neurog2 are key determinants of a dynamic network that controls whether neural stem cells self-renew, generate cortical neurons, or generate basal progenitor cells, a mechanism that has marked parallels with the transcriptional control of embryonic stem cell self-renewal.

Gene duplication is a major driver of evolutionary divergence. In most vertebrates a single PAX6 gene encodes a transcription factor required for eye, brain, olfactory system, and pancreas development. In zebrafish, following a postulated whole-genome duplication event in an ancestral teleost, duplicates pax6a and pax6b jointly fulfill these roles. Mapping of the homozygously viable eye mutant sunrise identified a homeodomain missense change in pax6b, leading to loss of target binding. The mild phenotype emphasizes role-sharing between the co-orthologues. Meticulous mapping of isolated BACs identified perturbed synteny relationships around the duplicates. This highlights the functional conservation of pax6 downstream (3') control sequences, which in most vertebrates reside within the introns of a ubiquitously expressed neighbour gene, ELP4, whose pax6a-linked exons have been lost in zebrafish. Reporter transgenic studies in both mouse and zebrafish, combined with analysis of vertebrate sequence conservation, reveal loss and retention of specific cis-regulatory elements, correlating strongly with the diverged expression of co-orthologues, and providing clear evidence for evolution by subfunctionalization.

Compromised heat shock protein 90 (Hsp90) function reveals cryptic phenotypes in flies and plants. These observations were interpreted to suggest that this molecular stress-response chaperone has a capacity to buffer underlying genetic variation. Conversely, the protective role of Hsp90 could account for the variable penetrance or severity of some heritable developmental malformations in vertebrates. Using zebrafish as a model, we defined Hsp90 inhibitor levels that did not induce a heat shock response or perturb phenotype in wild-type strains. Under these conditions the severity of the recessive eye phenotype in sunrise, caused by a pax6b mutation, was increased, while in dreumes, caused by a sufu mutation, it was decreased. In another strain, a previously unobserved spectrum of severe structural eye malformations, reminiscent of anophthalmia, microphthalmia, and nanophthalmia complex in humans, was uncovered by this limited inhibition of Hsp90 function. Inbreeding of offspring from selected unaffected carrier parents led to significantly elevated malformation frequencies and revealed the oligogenic nature of this phenotype. Unlike in Drosophila, Hsp90 inhibition can decrease developmental stability in zebrafish, as indicated by increased asymmetric presentation of anophthalmia, microphthalmia, and nanophthalmia and sunrise phenotypes. Analysis of the sunrise pax6b mutation suggests a molecular mechanism for the buffering of mutations by Hsp90. The zebrafish studies imply that mild perturbation of Hsp90 function at critical developmental stages may underpin the variable penetrance and expressivity of many developmental anomalies where the interaction between genotype and environment plays a major role.

Objective: The main objective of this study was to assess whether objective vestibular, oculomotor, and balance functions were impaired in children with a current diagnosis of concussion with vestibular and/or ocular symptoms. Setting: Data were collected in a vestibular/ocular clinical laboratory. Patient participants were recruited from a concussion clinic in a children's hospital. Participants: Thirty-three children aged 8 to 17 years with a current diagnosis of concussion and vestibular and/or ocular symptoms and 30 children without concussion. Design: Crosssectional single-visit study.Main OutcomeMeasures: Eye-tracking rotary chair oculomotor and vestibularmeasures, vestibular evoked potentials, and static posturography. Results: There were no statistically significant differences on any clinical measure between children with concussion and children without concussion. Younger children without concussion performed significantly worse on several rotary chair and balance measures compared with older children without concussion. Conclusions: No vestibular, oculomotor, or balance measures were significantly different between children with concussion and children without concussion, suggesting these measures may not be useful in the evaluation of a child with concussion and vestibular and/or oculomotor symptoms. Future research should investigate age effects and other vestibular and oculomotor tests to identify objective findings that better relate to vestibular and/or ocular symptoms in children with concussion. [ABSTRACT FROM AUTHOR]

Background--Patients with PCSK9 gene gain of function (GOF) mutations have a rare form of autosomal dominant hypercholesterolemia. However, data examining their clinical characteristics and geographic distribution are lacking. Furthermore, no randomized treatment study in this population has been reported. Methods and Results--We compiled clinical characteristics of PCSK9 GOF mutation carriers in a multinational retrospective, cross-sectional, observational study. We then performed a randomized placebo-phase, double-blind study of alirocumab 150 mg administered subcutaneously every 2 weeks to 13 patients representing 4 different PCSK9 GOF mutations with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL on their current lipid-lowering therapies at baseline. Observational study: among 164 patients, 16 different PCSK9 GOF mutations distributed throughout the gene were associated with varying severity of untreated LDL-C levels. Coronary artery disease was common (33%; average age of onset, 49.4 years), and untreated LDL-C concentrations were higher compared with matched carriers of mutations in the LDLR (n=2126) or apolipoprotein B (n=470) genes. Intervention study: in PCSK9 GOF mutation patients randomly assigned to receive alirocumab, mean percent reduction in LDL-C at 2 weeks was 62.5% (P<0.0001) from baseline, 53.7% compared with placebo-treated PCSK9 GOF mutation patients (P=0.0009; primary end point). After all subjects received 8 weeks of alirocumab treatment, LDL-C was reduced by 73% from baseline (P<0.0001). Conclusions--PCSK9 GOF mutation carriers have elevated LDL-C levels and are at high risk of premature cardiovascular disease. Alirocumab, a PCSK9 antibody, markedly lowers LDL-C levels and seems to be well tolerated in these patients. [ABSTRACT FROM AUTHOR]