Mutational and secondary structural analysis of the basolateral sorting signal of the polymeric immunoglobulin receptor.

The 17-juxtamembrane cytoplasmic residues of the polymeric immunoglobulin receptor contain an autonomous basolateral targeting signal that does not mediate rapid endocytosis (Casanova, J. E., G. Apodaca, and K. E. Mostov. Cell. 66:65-75). Alanine-scanning mutagenesis identifies three residues in this region, His656, Arg657, and Val660, that are most essential for basolateral sorting and two residues, Arg655 and Tyr668, that play a lesser role in this process. Progressive truncations suggested that Ser664 and Ile665 might also play a role in basolateral sorting. However, mutation of these residues to Ala or internal deletions of these residues did not affect basolateral sorting, indicating that these residues are probably not required for basolateral sorting. Two-dimensional NMR spectroscopy of a peptide corresponding to the 17-mer signal indicates that the sequence Arg658-Asn-Val-Asp661 has a propensity to adopt a beta-turn in solution. Residues COOH-terminal to the beta-turn (Arg662 to Arg669) seem to take up a nascent helix structure in solution. Substitution of Val660 with Ala destabilizes the turn, while mutation of Arg657 to Ala does not appear to affect the turn structure. Neither mutation detectably altered the stability of the nascent helix in the COOH-terminal portion of the peptide

The effects of permeability-driven water transport on the evolution of CM parent bodies

Accepted versio

The relevance of the evolution of experimental studies for the interpretation and evaluation of some trace physical evidence

In order for trace evidence to have a high evidential value, experimental studies which mimic the forensic reality are of fundamental importance. Such primary level experimentation is crucial to establish a coherent body of theory concerning the generation, transfer and persistence of different forms of trace physical evidence. We contend that the forensic context, at whatever scale, will be specific to each individual forensic case and this context in which a crime takes place will influence the properties of trace evidence. it will, therefore, be necessary in many forensic cases to undertake secondary level experimental studies that incorporate specific variables pertinent to a particular case and supplement the established theory presented in the published literature. Such studies enable a better understanding of the specific forensic context and thus allow More accurate collection, analysis and interpretation of the trace physical evidence to be achieved. This paper presents two cases where the findings of secondary level experimental studies undertaken to address specific issues particular to two forensic investigations proved to be important. Specific pre-, syn- and post-forensic event factors were incorporated into the experimental design and proved to be invaluable in the recovery, analysis and in achieving accurate interpretations of both soil evidence from footwear and glass trace evidence from a broken window.These Studies demonstrate that a fuller understanding of the specific context within which trace physical evidence is generated and subsequently collected, as well as an understanding of the behaviour of certain forms of trace physical evidence under specific conditions, can add evidentiary weight to the analysis and interpretation of that evidence and thus help a court with greater certainty where resources (time and cost) permit

Evaluation of a Commercial Enzyme Linked Immunosorbent Assay (ELISA) for the Determination of the Neurotoxin BMAA in Surface Waters

The neurotoxin ß-N-methylamino-L-alanine (BMAA) is suspected to play a role in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Because BMAA seems to be produced by cyanobacteria, surface waters are screened for BMAA. However, reliable analysis of BMAA requires specialized and expensive equipment. In 2012, a commercial enzyme-linked immunosorbent assay (ELISA) for determination of BMAA in surface waters was released. This kit could enable fast and relatively cheap screening of surface waters for BMAA. The objective of this study was to determine whether the BMAA ELISA kit was suitable for the determination of BMAA concentrations in surface waters. We hypothesised that the recovery of spiked samples was close to 100% and that the results of unspiked sample analysis were comparable between ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. However, we found that recovery was higher than 100% in most spiked samples, highest determined recovery was over 400%. Furthermore, the ELISA gave a positive signal for nearly each tested sample while no BMAA could be detected by LC-MS/MS. We therefore conclude that in its current state, the kit is not suitable for screening surface waters for BMAA

What should medical students be taught about abortion? An evaluation of student attitudes towards their abortion teaching and their future involvement in abortion care

BACKGROUND: One in three women in the United Kingdom (UK) will have an abortion before age 45, making abortion provision an essential aspect of reproductive healthcare. Despite this, abortion remains ethically contested and stigmatised, with variable teaching in UK medical schools and concerns about falling numbers of doctors willing to participate in abortion care. University College London Medical School (UCLMS) has designed practical, inclusive, teaching that aims to give students an understanding of the importance of abortion care and prepare them to be competent practitioners in this area. This study aimed to determine students' opinions of this teaching and their wider attitudes towards abortion. METHODS: We invited all 357 final-year UCL medical students to complete an online survey consisting of closed-ended questions, exploring their opinions on their abortion teaching, their personal beliefs about abortion and their future willingness to be involved in abortion care. We analysed responses using non-parametric tests. RESULTS: One hundred and forty-six questionnaires (41% response rate) showed 83% of students identified as pro-choice (agree with the right to choose an abortion). Fifty-seven percent felt they received the right amount of abortion teaching, 39% would have liked more and 4% stated they received too much. There was no correlation between students' attitudes to abortion and the rating of teaching; both pro-choice and pro-life (opposed to the right to choose an abortion) students generally rated the teaching as important and valued the range of methods used. Students requested more simulated practice speaking to patients requesting an abortion. Students with pro-life beliefs expressed lower willingness to discuss, refer, certify and provide future abortions. Students interested in careers in specialties where they may encounter abortion were more likely to be pro-choice than pro-life. CONCLUSIONS: The majority of participating UCL medical students were pro-choice and willing to be involved in future abortion care. Efforts to make teaching on abortion practical, engaging, sensitive and inclusive were appreciated. As well as preparing students to be competent and caring practitioners, the teaching appears to contribute towards them viewing abortion as an essential aspect of women's healthcare, and may contribute to destigmatising abortion

Strength and endurance training reduces the loss of eccentric hamstring torque observed after soccer specific fatigue

Objectives: To investigate the effect of two hamstring training protocols on eccentric peak torque before and after soccer specific fatigue. Participants: Twenty-two university male soccer players. Design: Isokinetic strength tests were performed at 60°/s pre and post fatigue, before and after 2 different training interventions. A 45-minute soccer specific fatigue modified BEAST protocol (M-BEAST) was used to induce fatigue. Players were randomly assigned to a 4 week hamstrings conditioning intervention with either a maximum strength (STR) or a muscle endurance (END) emphasis. Main outcome measures: The following parameters were evaluated:– Eccentric peak torque (EccPT), angle of peak torque (APT), and angle specific torques at knee joint angles of 10°, 20°, 30°, 40°, 50°, 60°, 70°, 80° and 90°. Results: There was a significant effect of the M-BEAST on the Eccentric torque angle profile before training as well as significant improvements in post-fatigue torque angle profile following the effects of both strength and muscle endurance interventions. Conclusions: Forty-five minutes of simulated soccer activity leads to reduced eccentric hamstring torque at longer muscle lengths. Short-term conditioning programs (4-weeks) with either a maximum strength or a muscular endurance emphasis can equally reduce fatigue induced loss of strength over this time period

On The Power of Tree Projections: Structural Tractability of Enumerating CSP Solutions

The problem of deciding whether CSP instances admit solutions has been deeply studied in the literature, and several structural tractability results have been derived so far. However, constraint satisfaction comes in practice as a computation problem where the focus is either on finding one solution, or on enumerating all solutions, possibly projected to some given set of output variables. The paper investigates the structural tractability of the problem of enumerating (possibly projected) solutions, where tractability means here computable with polynomial delay (WPD), since in general exponentially many solutions may be computed. A general framework based on the notion of tree projection of hypergraphs is considered, which generalizes all known decomposition methods. Tractability results have been obtained both for classes of structures where output variables are part of their specification, and for classes of structures where computability WPD must be ensured for any possible set of output variables. These results are shown to be tight, by exhibiting dichotomies for classes of structures having bounded arity and where the tree decomposition method is considered

Distinguishing choroidal nevi from melanomas using the MOLES algorithm: Evaluation in an ocular nevus clinic

OBJECTIVE: The aim of this study was to determine the sensitivity and specificity of the MOLES scoring system in differentiating choroidal melanomas from nevi according to Mushroom shape, Orange pigment, Large tumor size, Enlarging tumor, and Subretinal fluid (SRF). METHODS: Color photographs, fundus-autofluorescence images, and optical coherence tomography of 222 melanocytic choroidal tumors were reviewed. Each MOLES feature was retrospectively scored between 0 and 2 and tumors categorized as "common nevus,""low-risk nevus,""high-risk nevus,"and "probable melanoma"according to the total score. MOLES scores were compared with the experts' diagnosis of melanoma. RESULTS: The MOLES scoring system indicated melanoma in all 81 tumors diagnosed as such by ocular oncologists (100% sensitivity) and nevus in 135 of 141 tumors given this diagnosis by these experts (95.7% specificity). Of the 6 tumors with discordant diagnoses, 4 had basal diameters exceeding 6 mm, all with SRF and/or orange pigment, and 2 small tumors showed either significant SRF with traces of orange pigment, or vice versa. CONCLUSIONS: The MOLES system for diagnosing melanocytic choroidal tumors compares well with expert diagnosis but needs to be evaluated when deployed by ophthalmologists and community optometrists in a wide variety of working environments

The prenatal ultrasonographic detection of myelomeningocele in patients referred to Children's Hospital Medical Center: a cross sectional study

BACKGROUND: To find out about the prenatal diagnosis rate of myelomeningocele (MMC) by ultrasound scan in patients referred to the Children's Hospital Medical Center in Tehran, Iran from July 2004 to July 2005. METHODS: We included 140 children born with MMC and who were referred for management, surgery and treatment of complications associated with it. The ultrasound reports were examined. Data on sex, age, location of MMC, time of prenatal ultrasound and the trimester in which the diagnosis was made along with the results of the diagnosis (MMC, hydrocephalus, or both), were collected. RESULTS: Among the studied patients, 136 (97.1%) cases had prenatal ultrasound, amongst those, 58 (42.6%) sonographic evaluations were diagnostic for hydrocephalus and/or MMC. The prenatal ultrasound was positive for MMC in 16 (11.8%), hydrocephalus in 25 (18.4%) and both MMC and hydrocephalus in 17 (12.5%) cases. Among all cases with prenatal diagnosis of MMC, 3.4% were detected in the first, 31% in the second and 65.5% in the third trimester. Thoracic/thoracolumbar lesions were found prenatally in 40% of cases, which is significantly higher than the detection rate of other locations including cervical/cervicothoracic and lumbar/lumbosacral/sacral regions diagnosed only in 0% and 21% of cases respectively. CONCLUSION: There is a large difference between the detection rate of our population (24.3%) compared to others (68%). Pregnant women should have an ultrasound at 20–22 week for detection of congenital anomalies including MMC

Pneumatic compression devices for in-home management of lymphedema: two case reports

The two patients in this case series had experienced long-term difficulty controlling lymphedema at home. Both patients had used numerous home therapies, including older-generation intermittent pneumatic compression devices, without success. The Flexitouch® system, an advanced pneumatic device, was prescribed to assist them with in-home efforts by providing therapy to their affected limbs in addition to the lower trunk area for the patient with lymphedema of the lower extremity; and the trunk, chest wall, and shoulder areas for the patient with lymphedema of the upper extremity. Both patients achieved successful home maintenance of lymphedema, as judged by limb volume, clinical observations, and subjective patient impressions, after incorporating the Flexitouch® system. Neither patient experienced the deleterious effects (worsening genital edema; fibrotic cuff development) that they had experienced with the older-generation intermittent pneumatic compression devices they had previously used. Incorporating the Flexitouch® system as part of maintenance may improve success for lymphedema patients who have previously struggled with in-home management