Implementation of universal newborn bloodspot screening for sickle cell disease and other clinically significant haemoglobinopathies in England: screening results for 2005–7

Early results from the National Health Service Sickle Cell and Thalassaemia Screening programme covering the whole of England are reported following the implementation of the national newborn blood-spot screening programme. Of the 13 laboratories performing screening, 10 chose high-performance liquid chromatography as the first screen, with isoelectric focusing as the second confirmatory test. Screening results for April 2005 to March 2007 are presented and include data from all the laboratories screening newborns in England, and almost 1.2 million infants. The screen-positive results show a national birth prevalence of almost 1 in 2000. The birth prevalence in London is five times that of most of the rest of the country. Over 17 000 carriers have been identified. Approximately seven per 1000 samples are reported as post-transfusion with wide ethnic category variation. Given the prevalence of the conditions, and coverage by ethnicity, 3–4 screen-positive cases could be missed each year. National implementation of newborn screening in England has increased the number of children identified with sickle cell disease, in many areas almost doubling the workload. Underascertainment of the condition has allowed a downplaying of the scale of need. It may also have contributed to infant mortality rates in urban areas as babies died without a diagnosis or treatment. The value of a co-ordinated national approach to policy development and implementation is emphasised by the English experience. The programme provides a model for Europe as well as other countries with significant minority populations, such as Canada. Potentially it also offers important lessons for Africa where the World Health Organization is supporting the introduction of newborn screening

Neurological complications following extrusion of sodium hypochlorite solution during root canal treatment.

AIM: To report the presentation and management of two cases with neurological complications secondary to the extrusion of sodium hypochlorite solution into the facial soft tissues during root canal treatment. SUMMARY: The clinical features, with particular emphasis on nerve deficit following inadvertent extrusion of sodium hypochlorite, are discussed and its management highlighted. Early and aggressive treatment is advocated following such incidents in order to reduce potentially serious complications. KEY LEARNING POINTS: *Neurological sequelae can follow inadvertent hypochlorite extrusion. *Early recognition may avert a potentially more serious outcome. *Active hospital treatment including intravenous steroids and antibiotics is recommended

The effect of ADC resolution on concurrent, multiband, direct RF sampling receivers

Connectivity using interband frequencies in 4G and 5G radio access networks, for example, carrier aggregation or dual-connectivity, incurs high receiver complexity and power consumption, in particular, when implemented using multiple radio units. Employing concurrent, multiband, direct RF sampling in a single radio chain architecture reduces the RF component count, leading to lower receiver complexity and power consumption. For this architecture, as the composite signal from multiple concurrent bands is digitized by a common analog-to-digital converter (ADC), the bit resolution critically affects system performance. In this paper, the effect of ADC resolution on the error vector magnitude (EVM) and Block Error Rate (BLER) performance of a concurrent, multiband, direct RF sampling receiver is investigated. Simulation and hardware measurement of a tri-band Long Term Evolution (LTE) system supporting three simultaneously active channels at 888 MHz, 1.92 GHz and 2.52 GHz is evaluated when reducing the ADC resolution from 8 to 3 bits. Interband interference measurements demonstrate that the multiband, direct RF sampling, wideband LTE receiver remains 3GPP compliant at 4-bit ADC resolution with the signal-to-noise-ratio (SNR) desensitization over a single-band receiver limited to 9 dB in the 888 MHz band

Large salp bloom export from the upper ocean and benthic community response in the abyssal northeast Pacific: Day to week resolution

A large bloom of Salpa spp. in the northeastern Pacific during the spring of 2012 resulted in a major deposition of tunics and fecal pellets on the seafloor at ∼ 4000 m depth (Sta. M) over a period of 6 months. Continuous monitoring of this food pulse was recorded using autonomous instruments: sequencing sediment traps, a time‐lapse camera on the seafloor, and a bottom‐transiting vehicle measuring sediment community oxygen consumption (SCOC). These deep‐sea measurements were complemented by sampling of salps in the epipelagic zone by California Cooperative Ocean Fisheries Investigations. The particulate organic carbon (POC) flux increased sharply beginning in early March, reaching a peak of 38 mg C m−2 d−1 in mid‐April at 3400 m depth. Salp detritus started appearing in images of the seafloor taken in March and covered a daily maximum of 98% of the seafloor from late June to early July. Concurrently, the SCOC rose with increased salp deposition, reaching a high of 31 mg C m−2 d−1 in late June. A dominant megafauna species, Peniagone sp. A, increased 7‐fold in density beginning 7 weeks after the peak in salp deposition. Estimated food supply from salp detritus was 97–327% of the SCOC demand integrated over the 6‐month period starting in March 2012. Such large episodic pulses of food sustain abyssal communities over extended periods of time

Large salp bloom export from the upper ocean and benthic community response in the abyssal northeast Pacific: Day to week resolution

Abstract A large bloom of Salpa spp. in the northeastern Pacific during the spring of 2012 resulted in a major deposition of tunics and fecal pellets on the seafloor at , 4000 m depth (Sta. M) over a period of 6 months. Continuous monitoring of this food pulse was recorded using autonomous instruments: sequencing sediment traps, a timelapse camera on the seafloor, and a bottom-transiting vehicle measuring sediment community oxygen consumption (SCOC). These deep-sea measurements were complemented by sampling of salps in the epipelagic zone by California Cooperative Ocean Fisheries Investigations. The particulate organic carbon (POC) flux increased sharply beginning in early March, reaching a peak of 38 mg C m 22 d 21 in mid-April at 3400 m depth. Salp detritus started appearing in images of the seafloor taken in March and covered a daily maximum of 98% of the seafloor from late June to early July. Concurrently, the SCOC rose with increased salp deposition, reaching a high of 31 mg C m 22 d 21 in late June. A dominant megafauna species, Peniagone sp. A, increased 7-fold in density beginning 7 weeks after the peak in salp deposition. Estimated food supply from salp detritus was 97-327% of the SCOC demand integrated over the 6-month period starting in March 2012. Such large episodic pulses of food sustain abyssal communities over extended periods of time

Molecular Recognition Effects in Atomistic Models of Imprinted Polymers

In this article we present a model for molecularly imprinted polymers, which considers both complexation processes in the pre-polymerization mixture and adsorption in the imprinted structures within a single consistent framework. As a case study we investigate MAA/EGDMA polymers imprinted with pyrazine and pyrimidine. A polymer imprinted with pyrazine shows substantial selectivity towards pyrazine over pyrimidine, thus exhibiting molecular recognition, whereas the pyrimidine imprinted structure shows no preferential adsorption of the template. Binding sites responsible for the molecular recognition of pyrazine involve one MAA molecule and one EGDMA molecule, forming associations with the two functional groups of the pyrazine molecule. Presence of these specific sites in the pyrazine imprinted system and lack of the analogous sites in the pyrimidine imprinted system is directly linked to the complexation processes in the pre-polymerization solution. These processes are quite different for pyrazine and pyrimidine as a result of both enthalpic and entropic effects

Genetic evaluation of suspected osteogenesis imperfecta (OI)

Osteogenesis imperfecta (OI) is probably the most common genetic form of fracture predisposition. The term OI encompasses a broad range of clinical presentations that may be first apparent from early in pregnancies to late in life, reflecting the extent of bone deformity and fracture predisposition at different stages of development or postnatal ages. Depending on the age of presentation, OI can be difficult to distinguish from some other genetic and nongenetic causes of fractures, including nonaccidental injury (abuse). The strategies for evaluation and the testing discussed here provide guidelines for evaluation that should help to distinguish among causes for fracture and bone deformity

Hypophosphatasia

Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity. The prevalence of severe forms of the disease has been estimated at 1/100 000

Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles

<p>Abstract</p> <p>Background</p> <p>Mild hypophosphatasia (HPP) phenotype may result from <it>ALPL </it>gene mutations exhibiting residual alkaline phosphatase activity or from severe heterozygous mutations exhibiting a dominant negative effect. In order to determine the cause of our failure to detect a second mutation by sequencing in patients with mild HPP and carrying on a single heterozygous mutation, we tested the possible dominant effect of 35 mutations carried by these patients.</p> <p>Methods</p> <p>We tested the mutations by site-directed mutagenesis. We also genotyped 8 exonic and intronic <it>ALPL </it>gene polymorphisms in the patients and in a control group in order to detect the possible existence of a recurrent intronic mild mutation.</p> <p>Results</p> <p>We found that most of the tested mutations exhibit a dominant negative effect that may account for the mild HPP phenotype, and that for at least some of the patients, a second mutation in linkage disequilibrium with a particular haplotype could not be ruled out.</p> <p>Conclusion</p> <p>Mild HPP results in part from compound heterozygosity for severe and moderate mutations, but also in a large part from heterozygous mutations with a dominant negative effect.</p

Functional Diversity of Human Basic Helix-Loop-Helix Transcription Factor TCF4 Isoforms Generated by Alternative 5′ Exon Usage and Splicing

BACKGROUND: Transcription factor 4 (TCF4 alias ITF2, E2-2, ME2 or SEF2) is a ubiquitous class A basic helix-loop-helix protein that binds to E-box DNA sequences (CANNTG). While involved in the development and functioning of many different cell types, recent studies point to important roles for TCF4 in the nervous system. Specifically, human TCF4 gene is implicated in susceptibility to schizophrenia and TCF4 haploinsufficiency is the cause of the Pitt-Hopkins mental retardation syndrome. However, the structure, expression and coding potential of the human TCF4 gene have not been described in detail. PRINCIPAL FINDINGS: In the present study we used human tissue samples to characterize human TCF4 gene structure and TCF4 expression at mRNA and protein level. We report that although widely expressed, human TCF4 mRNA expression is particularly high in the brain. We demonstrate that usage of numerous 5' exons of the human TCF4 gene potentially yields in TCF4 protein isoforms with 18 different N-termini. In addition, the diversity of isoforms is increased by alternative splicing of several internal exons. For functional characterization of TCF4 isoforms, we overexpressed individual isoforms in cultured human cells. Our analysis revealed that subcellular distribution of TCF4 isoforms is differentially regulated: Some isoforms contain a bipartite nuclear localization signal and are exclusively nuclear, whereas distribution of other isoforms relies on heterodimerization partners. Furthermore, the ability of different TCF4 isoforms to regulate E-box controlled reporter gene transcription is varied depending on whether one or both of the two TCF4 transcription activation domains are present in the protein. Both TCF4 activation domains are able to activate transcription independently, but act synergistically in combination. CONCLUSIONS: Altogether, in this study we have described the inter-tissue variability of TCF4 expression in human and provided evidence about the functional diversity of the alternative TCF4 protein isoforms