Progressive myoclonic epilepsy with Fanconi syndrome

This report illustrates the difficulties in diagnosing complex cases and demonstrates how whole exome sequencing can resolve complex phenotypes

AMMECR1: a single point mutation causes developmental delay, midface hypoplasia and elliptocytosis

Background: Deletions in the Xq22.3–Xq23 region, inclusive of COL4A5, have been associated with a contiguous gene deletion syndrome characterised by Alport syndrome with intellectual disability (Mental retardation), Midface hypoplasia and Elliptocytosis (AMME). The extrarenal biological and clinical significance of neighbouring genes to the Alport locus has been largely speculative. We sought to discover a genetic cause for two half-brothers presenting with nephrocalcinosis, early speech and language delay and midface hypoplasia with submucous cleft palate and bifid uvula.Methods: Whole exome sequencing was undertaken on maternal half-siblings. In-house genomic analysis included extraction of all shared variants on the X chromosome in keeping with X-linked inheritance. Patient-specific mutants were transfected into three cell lines and microscopically visualised to assess the nuclear expression pattern of the mutant protein.Results: In the affected half-brothers, we identified a hemizygous novel non-synonymous variant of unknown significance in AMMECR1 (c.G530A; p.G177D), a gene residing in the AMME disease locus. Transfected cell lines with the p.G177D mutation showed aberrant nuclear localisation patterns when compared with the wild type. Blood films revealed the presence of elliptocytes in the older brother.Conclusions: Our study shows that a single missense mutation in AMMECR1 causes a phenotype of midface hypoplasia, mild intellectual disability and the presence of elliptocytes, previously reported as part of a contiguous gene deletion syndrome. Functional analysis confirms mutant-specific protein dysfunction. We conclude that AMMECR1 is a critical gene in the pathogenesis of AMME, causing midface hypoplasia and elliptocytosis and contributing to early speech and language delay, infantile hypotonia and hearing loss, and may play a role in dysmorphism, nephrocalcinosis and submucous cleft palate.<br/

Comparing FISP to Alternative Programs

Malawi has made the Farm Input subsidy Program (FISP) the major pillar of both the country’s agricultural development strategy and its social protection policies since 2005/06. Expenditure on the FISP has been high, ranging from 5.6% of the national budget in 2005/06 to 16.2% of the national budget in 2008/09. The general findings on FISP impacts are that the program has made a relatively small positive contribution to maize production and farm income. However, the program’s impact on rural poverty remains unclear

Effects of chronic exposure to thiamethoxam on larvae of the hoverfly Eristalis tenax (Diptera, Syrphidae)

There is widespread concern over the use of neonicotinoid pesticides in the agro-ecosystem, due in part to their high water solubility which can lead to widespread contamination of non-target areas including standing surface water. Most studies investigating the negative fitness consequences of neonicotinoids have focused on bees, with little research on the impact on other non-target insects. Here we examined the effect of exposure on the aquatic larval stages of the hoverfly Eristalis tenax L. (Diptera: Syrphidae) to a range of concentrations (control, 5, 15, 50, 100 and 500 ppb) of the neonicotinoid thiamethoxam; no published studies have thus far examined the effects of neonicotinoids on hoverflies. Survival was significantly lower when exposed to 500 ppb thiamethoxam, but this concentration exceeds that likely to be found in the field. We observed no effect on survival, development or any latent effects on adult activity budgets resulting from exposure to lower concentrations (up to 100 ppb). Our results suggest that E. tenax exposed as larvae to thiamethoxam are unlikely to be negatively impacted by this neonicotinoid under field conditions

Theory of radiation pressure on magneto–dielectric materials

We present a classical linear response theory for a magneto–dielectric material and determine the polariton dispersion relations. The electromagnetic field fluctuation spectra are obtained and polariton sum rules for their optical parameters are presented. The electromagnetic field for systems with multiple polariton branches is quantized in three dimensions and field operators are converted to 1–dimensional forms appropriate for parallel light beams. We show that the field–operator commutation relations agree with previous calculations that ignored polariton effects. The Abraham (kinetic) and Minkowski (canonical) momentum operators are introduced and their corresponding single–photon momenta are identified. The commutation relations of these and of their angular analogues support the identification, in particular, of the Minkowski momentum with the canonical momentum of the light. We exploit the Heaviside–Larmor symmetry of Maxwell's equations to obtain, very directly, the Einsetin–Laub force density for action on a magneto–dielectric. The surface and bulk contributions to the radiation pressure are calculated for the passage of an optical pulse into a semi–infinite sample

Multifactorial Analysis of Differences Between Sporadic Breast Cancers and Cancers Involving BRCA1 and BRCA2 Mutations

Background: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. Methods: Specimens of tumor tissue (5-µm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. Results: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers. Conclusions: Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients. [J Natl Cancer Inst 1998;90:1138-45

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Universal health coverage from multiple perspectives: a synthesis of conceptual literature and global debates

Background: There is an emerging global consensus on the importance of universal health coverage (UHC), but no unanimity on the conceptual definition and scope of UHC, whether UHC is achievable or not, how to move towards it, common indicators for measuring its progress, and its long-term sustainability. This has resulted in various interpretations of the concept, emanating from different disciplinary perspectives. This paper discusses the various dimensions of UHC emerging from these interpretations and argues for the need to pay attention to the complex interactions across the various components of a health system in the pursuit of UHC as a legal human rights issue. Discussion: The literature presents UHC as a multi-dimensional concept, operationalized in terms of universal population coverage, universal financial protection, and universal access to quality health care, anchored on the basis of health care as an international legal obligation grounded in international human rights laws. As a legal concept, UHC implies the existence of a legal framework that mandates national governments to provide health care to all residents while compelling the international community to support poor nations in implementing this right. As a humanitarian social concept, UHC aims at achieving universal population coverage by enrolling all residents into health-related social security systems and securing equitable entitlements to the benefits from the health system for all. As a health economics concept, UHC guarantees financial protection by providing a shield against the catastrophic and impoverishing consequences of out-of-pocket expenditure, through the implementation of pooled prepaid financing systems. As a public health concept, UHC has attracted several controversies regarding which services should be covered: comprehensive services vs. minimum basic package, and priority disease-specific interventions vs. primary health care. Summary: As a multi-dimensional concept, grounded in international human rights laws, the move towards UHC in LMICs requires all states to effectively recognize the right to health in their national constitutions. It also requires a human rights-focused integrated approach to health service delivery that recognizes the health system as a complex phenomenon with interlinked functional units whose effective interaction are essential to reach the equilibrium called UHC