Mental and Substance Use Disorders in Sub-Saharan Africa: Predictions of Epidemiological Changes and Mental Health Workforce Requirements for the Next 40 Years

The world is undergoing a rapid health transition, with an ageing population and disease burden increasingly defined by disability. In Sub-Saharan Africa the next 40 years are predicted to see reduced mortality, signalling a surge in the impact of chronic diseases. We modelled these epidemiological changes and associated mental health workforce requirements. Years lived with a disability (YLD) predictions for mental and substance use disorders for each decade from 2010 to 2050 for four Sub-Saharan African regions were calculated using Global Burden of Disease 2010 study (GBD 2010) data and UN population forecasts. Predicted mental health workforce requirements for 2010 and 2050, by region and for selected countries, were modelled using GBD 2010 prevalence estimates and recommended packages of care and staffing ratios for low- and middle-income countries, and compared to current staffing from the WHO Mental Health Atlas. Significant population growth and ageing will result in an estimated 130% increase in the burden of mental and substance use disorders in Sub-Saharan Africa by 2050, to 45 million YLDs. As a result, the required mental health workforce will increase by 216,600 full time equivalent staff from 2010 to 2050, and far more compared to the existing workforce. The growth in mental and substance use disorders by 2050 is likely to significantly affect health and productivity in Sub-Saharan Africa. To reduce this burden, packages of care for key mental disorders should be provided through increasing the mental health workforce towards targets outlined in this paper. This requires a shift from current practice in most African countries, involving substantial investment in the training of primary care practitioners, supported by district based mental health specialist teams using a task sharing model that mobilises local community resources, with the expansion of inpatient psychiatric units based in district and regional general hospitals.     

Shape Up or Ship Out: Can We Enhance Productivity in Coastal Aquaculture to Compete with Other Uses?

Coastal resources are coming under increasing pressure from competition between recreational, commercial and conservation uses. This is particularly so in coastal areas adjacent to major population centres. Given high recreational and conservation values in such areas, economic activities need to be highly efficient in order to persist. Management of these industries must therefore also encourage efficient production and full utilisation of the areas available. In order to achieve this, managers must first understand the level and drivers of productivity, and how these can be influenced. In this study, by way of illustration, the focus was on the Sydney rock oyster industry within Queensland''s Moreton Bay, a multiple use marine park with high recreational and conservation value adjacent to Australia’s third largest city. Productivity of the oyster industry in Moreton Bay is currently low compared to historic levels, and management has an objective of reversing this trend. It is unclear whether this difference is due to oyster farmers’ business choices and personal characteristics or whether varying environmental conditions in the Moreton Bay limit the capacity of the oyster industry. These require different management responses in order to enhance productivity. The study examined different productivity measures of the oyster industry using data envelopment analysis (DEA) to determine where productivity gains can be made and by how much. The findings suggest that the industry is operating at a high level of capacity utilisation, but a low level of efficiency. The results also suggest that both demographic and environmental conditions affect technical efficiency in the Bay, with water characteristics improvements and appropriate training potentially providing the greatest benefits to the industry. Methods used in this study are transferable to other industries and provide a means by which coastal aquaculture may be managed to ensure it remains competitive with other uses of coastal resources.     

Predicting the impact of the 2011 conflict in Libya on population mental health: PTSD and depression prevalence and mental health service requirements

Background

Mental disorders are likely to be elevated in the Libyan population during the post-conflict period. We estimated cases of severe PTSD and depression and related health service requirements using modelling from existing epidemiological data and current recommended mental health service targets in low and middle income countries (LMIC’s).

Methods

Post-conflict prevalence estimates were derived from models based on a previously conducted systematic review and meta-regression analysis of mental health among populations living in conflict. Political terror ratings and intensity of exposure to traumatic events were used in predictive models. Prevalence of severe cases was applied to chosen populations along with uncertainty ranges. Six populations deemed to be affected by the conflict were chosen for modelling: Misrata (population of 444,812), Benghazi (pop. 674,094), Zintan (pop. 40,000), displaced people within Tripoli/Zlitan (pop. 49,000), displaced people within Misrata (pop. 25,000) and Ras Jdir camps (pop. 3,700). Proposed targets for service coverage, resource utilisation and full-time equivalent staffing for management of severe cases of major depression and post-traumatic stress disorder (PTSD) are based on a published model for LMIC’s.

Findings

Severe PTSD prevalence in populations exposed to a high level of political terror and traumatic events was estimated at 12.4% (95%CI 8.5–16.7) and was 19.8% (95%CI 14.0–26.3) for severe depression. Across all six populations (total population 1,236,600), the conflict could be associated with 123,200 (71,600–182,400) cases of severe PTSD and 228,100 (134,000–344,200) cases of severe depression; 50% of PTSD cases were estimated to co-occur with severe depression. Based upon service coverage targets, approximately 154 full-time equivalent staff would be required to respond to these cases sufficiently which is substantially below the current level of resource estimates for these regions.

Discussion

This is the first attempt to predict the mental health burden and consequent service response needs of such a conflict, and is crucially timed for Libya.     

UV damage of collagen: insights from model collagen peptides

Fibrils of Type I collagen in the skin are exposed to ultraviolet (UV) light and there have been claims that collagen photo-degradation leads to wrinkles and may contribute to skin cancers. To understand the effects of UV radiation on collagen, Type I collagen solutions were exposed to the UV-C wavelength of 254 nm for defined lengths of time at 4°C. Circular dichroism (CD) experiments show that irradiation of collagen leads to high loss of triple helical content with a new lower thermal stability peak and SDS-gel electrophoresis indicates breakdown of collagen chains. To better define the effects of UV radiation on the collagen triple-helix, the studies were extended to peptides which model the collagen sequence and conformation. CD studies showed irradiation for days led to lower magnitudes of the triple-helix maximum at 225 nm and lower thermal stabilities for two peptides containing multiple Gly-Pro-Hyp triplets. In contrast, the highest radiation exposure led to little change in the T(m) values of (Gly-Pro-Pro)(10) and (Ala-Hyp-Gly)(10) , although (Gly-Pro-Pro)(10) did show a significant decrease in triple helix intensity. Mass spectroscopy indicated preferential cleavage sites within the peptides, and identification of some of the most susceptible sites of cleavage. The effect of radiation on these well defined peptides gives insight into the sequence and conformational specificity of photo-degradation of collagen.     

Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels.     

Isomerization of a single aspartyl residue of anti-epidermal growth factor receptor immunoglobulin gamma2 antibody highlights the role avidity plays in antibody activity

A new isoform of the light chain of a fully human monoclonal immunoglobulin gamma2 (IgG2) antibody panitumumab against human epidermal growth factor receptor (EGFR) was generated by in vitro aging. The isoform was attributed to the isomerization of aspartate 92 located between phenylalanine 91 and histidine 93 residues in the antigen-binding region. The isomerization rate increased with increased temperature and decreased pH. A size-exclusion chromatography binding assay was used to show that one antibody molecule was able to bind two soluble extracellular EGFR molecules in solution, and isomerization of one or both Asp-92 residues deactivated one or both antigen-binding regions, respectively. In addition, isomerization of Asp-92 showed a decrease in in vitro potency as measured by a cell proliferation assay with a 32D cell line that expressed the full-length human EGFR. The data indicate that antibodies containing either one or two isomerized residues were not effective in inhibiting EGFR-mediated cell proliferation, and that two unmodified antigen binding regions were needed to achieve full efficacy. For comparison, the potency of an intact IgG1 antibody cetuximab against the same receptor was correlated with the bioactivity of its individual antigen-binding fragments. The intact IgG1 antibody with two antigen-binding fragments was also much more active in suppressing cell proliferation than the individual fragments, similar to the IgG2 results. These results indicated that avidity played a key role in the inhibition of cell proliferation by these antibodies against the human EGFR, suggesting that their mechanisms of action are similar.     

Functional analyses of RNA structures shared between the internal ribosome entry sites of hepatitis C virus and the picornavirus porcine teschovirus 1 Talfan

The internal ribosome entry site (IRES) of porcine teschovirus 1 (PTV-1), a member of the Picornaviridae family, is quite distinct from other well-characterized picornavirus IRES elements, but it displays functional similarities to the IRES from hepatitis C virus (HCV), a member of the Flaviviridae family. In particular, a dominant negative mutant form of eIF4A does not inhibit the activity of the PTV-1 IRES. Furthermore, there is a high level (ca. 50%) of identity between the PTV-1 and HCV IRES sequences. A secondary-structure model of the whole PTV-1 IRES has been derived which includes a pseudoknot. Validation of specific features within the model has been achieved by mutagenesis and functional assays. The differences and similarities between the PTV-1 and HCV IRES elements should assist in defining the critical features of this type of IRES.     

The Landscape of Leadership in Environmental Governance: a Case Study from Solomon Islands

Sustainability science suggests a core set of factors that foster significant change in governance, with leaders and entrepreneurs often identified as the main instigators. Discussions of leadership in governance transformations often focus on key charismatic people, underplaying contestation and the complex landscape of leadership. We present an empirical study that uses a participatory network mapping approach to provide a broader examination of leadership in integrated conservation and development. We use the Coral Triangle Initiative in Solomon Islands as an example of potential transformation in environmental governance across multiple objectives. Our analysis shows that actants, other than key individuals, enact leadership. We illustrate that a different suite of actants are providing leadership for each of the three Coral Triangle Initiative objectives. Actants can enact leadership by positively and negatively influencing different goals to varying extents. Our study illustrates the potential of broader and more nuanced understandings of leadership in environmental governance.     

Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome

CIZ1 forms large assemblies at the inactive X chromosome (Xi) in female fibroblasts in an Xist lncRNA-dependent manner and is required for accurate maintenance of polycomb targets genome-wide. Here we address requirements for assembly formation and show that CIZ1 undergoes two direct interactions with Xist, via independent N- and C-terminal domains. Interaction with Xist, assembly at Xi, and complexity of self-assemblies formed in vitro are modulated by two alternatively spliced glutamine-rich prion-like domains (PLD1 and 2). PLD2 is dispensable for accumulation at existing CIZ1–Xi assemblies in wild-type cells but is required in CIZ1-null cells where targeting, assembly, and enrichment for H3K27me3 and H2AK119ub occur de novo. In contrast, PLD1 is required for both de novo assembly and accumulation at preexisting assemblies and, in vitro, drives formation of a stable fibrillar network. Together they impart affinity for RNA and a complex relationship with repeat E of Xist. These data show that alternative splicing of two PLDs modulates CIZ1’s ability to build large RNA–protein assemblies.