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We describe studies undertaken in support of the Far‐infrared Outgoing Radiation Understanding and Monitoring mission, European Space Agency's ninth Earth Explorer, designed to investigate whether airborne observations of far‐infrared radiances can provide beneficial information on mid and upper tropospheric water vapor concentrations. Initially we perform a joint temperature and water vapor retrieval and show that the water vapor retrieval exploiting far‐infrared measurements from the Tropospheric Airborne Fourier Transform Spectrometer (TAFTS) shows improvement over the a‐priori Unified Model global forecast when compared to in situ dropsonde measurements. For this case the improvement is particularly noticeable in the mid‐upper troposphere. Equivalent retrievals using mid‐infrared radiances measured by the Airborne Research Interferometer Evaluation System (ARIES) show much reduced performance, with the degrees of freedom for signal (DFS), reduced by a factor of almost 2. Further sensitivity studies show that this advantage is decreased, but still present when the spectral resolution of the TAFTS measurements is reduced to match that of ARIES. The beneficial role of the far infrared for this case is further confirmed by performing water vapor only retrievals using ARIES and TAFTS individually, and then in combination. We find that the combined retrieval has a DFS value of 6.7 for water vapor, marginally larger than that obtained for the TAFTS retrieval and almost twice as large as that obtained for ARIES. These results provide observational support of theoretical studies highlighting the potential improvement that far‐infrared observations could bring for the retrieval of tropospheric water vapor. Plain Language Summary: The Far‐infrared Outgoing Radiation Understanding and Monitoring (FORUM) mission has been selected as the European Space Agency's ninth Earth Explorer. Far‐infrared Outgoing Radiation Understanding and Monitoring will be the first mission to make high spectral resolution measurements of the Earth's outgoing energy in a region of the spectrum known as the far‐infrared. These observations will complement our existing knowledge of the Earth's outgoing spectrum in the mid‐infrared, where measurements have been made for many years. This paper describes a study in support of FORUM, using unique aircraft‐based observations of far‐ and mid‐infrared spectrally resolved radiation, complemented by measurements of the vertical profile of water vapor and temperature below the aircraft from dropsonde. We infer the humidity and temperature profile from the radiation observations and show that using the far‐infrared observations improves our ability to properly capture the observed dropsonde behavior compared to using the mid‐infrared measurements alone. This is the first time that far‐infrared aircraft observations have been used to demonstrate an improvement in our ability to characterize atmospheric humidity. It suggests that FORUM measurements may be able to enhance our understanding of atmospheric water vapor, with associated benefits for climate prediction. Key Points: Co‐incident mid‐ and far‐infrared upwelling radiance spectra have been observed from aircraft under clear sky conditionsHumidity and temperature retrievals show improved information content for the far‐infrared over the mid‐infrared for these instrumentsThis advantage is retained when water vapor only retrievals are performed [ABSTRACT FROM AUTHOR]

Background: Non‐attendance at diabetes outpatient appointments is a sizeable problem worldwide and has been associated with suboptimal health outcomes. We aimed to describe the characteristics, health outcomes and reasons given for non‐attendance at doctor‐ or nurse‐led diabetes appointments, and interventions to improve attendance. Methods: PubMed, EMBASE, CINAHL and PsychInfo were searched from database inception to February 2019. Included articles were peer‐reviewed, published in English, related to adults or young people with type 1 or type 2 diabetes, and addressed one of the above aspects of non‐attendance. Studies were excluded if reporting on other types of diabetes or reviewing attendance at structured education, retinal screening, paediatric, antenatal, podiatry or dietetic clinics. Results: Thirty‐four studies of varied designs were identified (15 observational, 1 randomized control trial, 9 qualitative, 5 surveys, 4 service improvements). The definition of non‐attendance varied. Younger adults, smokers and those with financial pressures were less likely to attend. Non‐attendance was associated with higher HbA1c; other outcomes were varied but typically worse in non‐attenders. Reasons for non‐attendance in qualitative studies fell into three categories: balancing the costs and benefits of attendance, coping strategies, and the relationships between the person with diabetes and healthcare professionals. Interventions included appointment management strategies, service improvements, patient navigators and WebCam appointments. Conclusions: Non‐attendance is only partially explained by logistical issues. Qualitative studies suggest complex psychosocial factors are involved. Interventions have progressed from simple appointment reminders in an attempt to address some of the psycho‐social determinants, but more work is needed to improve attendance. [ABSTRACT FROM AUTHOR]

The Royal College of Psychiatrists Liaison Faculty & Joint British Diabetes Societies (JBDS) for Inpatient Care guidelines for the management of diabetes in adults and children with psychiatric disorders in inpatient settings are available in full at: www.diabetes.org.uk/joint-british-diabetes-society and https://abcd.care/joint-british diabetes-societies-jbds-inpatient-care-group. This article summarizes the guidelines and recommendations. Commissioners are urged to ensure that the needs of people with diabetes and severe mental illness are specifically addressed in contracts with providers of inpatient care, and to avoid financial or other barriers to cross-organizational working and to ensure that patient-structured education is commissioned to meets the complex needs of people with diabetes and severe mental illness. Acute trusts are asked to develop joint pathways with mental health providers and facilitate multidisciplinary working and to screen for mental ill health in those admitted with acute complications of diabetes whose aetiology is unclear or not medically explained. Mental health trusts should create a diabetes register, screen for diabetes, particularly in those prescribed second-generation antipsychotics and ensure that staff are trained in managing and avoiding hypoglycaemia, and the safe use of insulin. Finally, clinical teams should ensure that all staff can access training in diabetes and mental health to support them to care for people with both diabetes and severe mental illness, develop local pathways for joint working and ensure best practice tariff criteria are met for diabetic ketoacidosis and hypoglycaemia, and for children and young people with diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Desert dust is one of the most important atmospheric ice‐nucleating aerosol species around the globe. However, there have been very few measurements of ice‐nucleating particle (INP) concentrations in dusty air close to desert sources. In this study we report the concentration of INPs in dust laden air over the tropical Atlantic within a few days' transport of one of the world's most important atmospheric sources of desert dust, the Sahara. These measurements were performed as part of the Ice in Clouds Experiment‐Dust campaign based in Cape Verde, during August 2015. INP concentrations active in the immersion mode, determined using a droplet‐on‐filter technique, ranged from around 102 m−3 at −12°C to around 105 m−3 at −23°C. There is about 2 orders of magnitude variability in INP concentration for a particular temperature, which is determined largely by the variability in atmospheric dust loading. These measurements were made at altitudes from 30 to 3,500 m in air containing a range of dust loadings. The ice active site density (ns) for desert dust dominated aerosol derived from our measurements agrees with several laboratory‐based parameterizations for ice nucleation by desert dust within 1 to 2 orders of magnitude. The small variability in ns values determined from our measurements (within about 1 order of magnitude) is striking given that the back trajectory analysis suggests that the sources of dust were geographically diverse. This is consistent with previous work, which indicates that desert dust's ice‐nucleating activity is only weakly dependent on source. [ABSTRACT FROM AUTHOR]

Trypanosoma brucei are extracellular kinetoplastid parasites transmitted by the blood-sucking tsetse fly. They are responsible for the fatal disease human African trypanosomiasis ( HAT), also known as sleeping sickness. In late-stage infection, trypanosomes cross the blood-brain barrier ( BBB) and invade the central nervous system ( CNS) invariably leading to coma and death if untreated. There is no available vaccine and current late-stage HAT chemotherapy consists of either melarsoprol, which is highly toxic causing up to 8% of deaths, or nifurtimox-eflornithine combination therapy ( NECT), which is costly and difficult to administer. There is therefore an urgent need to identify new late-stage HAT drug candidates. Here, we review how current imaging tools, ranging from fluorescent confocal microscopy of live immobilized cells in culture to whole-animal imaging, are providing insight into T. brucei biology, parasite-host interplay, trypanosome CNS invasion and disease progression. We also consider how imaging tools can be used for candidate drug screening purposes that could lead to new chemotherapies. [ABSTRACT FROM AUTHOR]

To cite this article: Liu X, Wang G, Hong X, Wang D, Tsai H-J, Zhang S, Arguelles L, Kumar R, Wang H, Liu R, Zhou Y, Pearson C, Ortiz K, Schleimer R, Holt P, Pongracic J, Price HE, Langman C, Wang X. Gene-vitamin D interactions on food sensitization: a prospective birth cohort study. Allergy 2011; 66: 1442-1448. Abstract Background: It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine whether cord blood VDD is associated with FS and whether such association can be modified by genetic variants in a prospective birth cohort. Methods: This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D < 11 ng/ml, and FS as specific IgE ≥ 0.35 kUA/l to any of eight common food allergens in early childhood. We genotyped potentially functional single-nucleotide polymorphisms (SNPs) in 11 genes known to be involved in regulating IgE and 25(OH)D concentrations. Logistic regressions were used to test the effects of VDD on FS individually and jointly with SNPs. Results: Among the 649 children, 44% had VDD and 37% had FS. When examined alone, VDD was not associated with FS. When examined jointly with SNPs, a significant interaction between IL4 gene polymorphism (rs2243250) and VDD (pinteraction = 0.003, pFDR = 0.10) was found: VDD increased the risk of FS among children carrying CC/CT genotypes (OR = 1.79, 95%CI: 1.15-2.77). Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). When all four SNPs were simultaneously considered, a strong gene-VDD interaction was evident (pinteraction = 9 × 10−6). Conclusions: Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene-vitamin D interaction on FS. [ABSTRACT FROM AUTHOR]

Aim Informing a person of their individual risk of developing a disease in the future may be sufficient to provide the person with the impetus to adopt risk reducing behaviours. The aim of this study was to determine if a personalised 10-year cardiovascular disease (CVD) risk estimate can increase physical activity and other risk reduction behaviours in adults at high risk of CVD. Methods Pilot 2 × 2 factorial randomised controlled trial conducted in Oxfordshire, UK including 194 adults at increased CVD risk (10-year CVD risk ⩾20%) recruited from four general practices. Main outcome measure at one month was physical activity measured by accelerometer. Results Median (IQR) age was 62.3 (54.9, 66.1) years, 67% were men and 19% had known diabetes. Mean (SD) total accelerometer counts per day was 297 × 10-3 (110 × 10-3) and activity of moderate or greater intensity was undertaken for 53 (22) minutes per day. In the 185 (95%) participants attending follow-up an increase in physical activity was not seen. There was a non-significant 0.5% (p = 0.56) greater increase in accelerometer counts in those receiving personalised CVD risk estimates. No significant within or between group changes were seen at one month in estimated 10-year CVD risk. A net 7% decrease in mean LDL cholesterol (p = 0.004) was seen in the intervention group despite similar increases in new prescriptions for lipid lowering therapies. Conclusion In adults at increased risk of CVD provision of personalised 10-year CVD risk estimates did not appear to increase physical activity or estimated CVD risk over a one-month period. [ABSTRACT FROM AUTHOR]

The article focuses on the role of community pharmacists in the delivery of diabetes care. Topics include the community pharmacists are a largely untapped resource in the delivery of diabetes care, growing number of people living with diabetes and increasing demand on healthcare services, and the pharmacies have longer opening hours than many general practice surgeries or secondary care outpatient facilities.

Wild Australian Sorghum species are a tertiary gene pool to grain sorghum [Sorghum bicolor (L.) Moench], and they are of interest to breeders because of their resistance to important insects and pathogens. However, strong reproductive barriers have prevented hybridization between S. bicolor and these wild species. The purpose of this study was to determine if the recessive lap allele (dominant allele lap = inhibition of alien pollen) would reduce or eliminate the pollen-pistil incompatibilities that prevent hybridization between S. bicolor and divergent Sorghum species. Cytoplasmic male-sterile S. bicolor plants, homozygous for the lap allele, were pollinated with three divergent Sorghum species, S. angustum Blake, S. nitidum (Vahl) Pers., and S. macrospermum Garber. The pollen of these three wild species readily germinated and the pollen tubes grew to the base of the S. bicolor ovary within 2 h after pollination. Hybrid embryos were detected in the S. bicolor florets 13 to 20 d post-pollination. Sorghum bicoior X S. angustum and S. bicolor X S. nitidum hybrids were obtained using embryo rescue followed by in vitro culture techniques and hybrids between S. bicolor and S. macrospermum were obtained by simply germinating the hybrid seed. These hybrids were confirmed by their morphological and cytological traits. These findings clearly demonstrate that the recessive lap allele circumvents pollen-pistil incompatibilities in the genus Sorghum and permits hybrids to be made between S. bicolor and species of the tertiary gene pool. [ABSTRACT FROM AUTHOR]

Sorghum [Sorghum bicolor (L) Moench] breeders have long recognized the importance of exotic germplasm and noncultivated sorghum races as sources of valuable genes for genetic improvement. The genus Sorghum consists of 25 species classified as five sections: Eusorghum, Chaetosorghum, Heterosorghum, Para-sorghum, and Stipo-sorghum. Species outside the Eu-sorghum section are sources of important genes for sorghum improvement, including those for insect and disease resistance, but these have not been used because of the failure of these species to cross with sorghum. An understanding of the biological nature of the incompatibility system(s) that prevent hybridization and/or seed development is necessary for the successful hybridization and introgression between sorghum and divergent Sorghum species. The objectives of this study were to determine the reason(s) for reproductive isolation between Sorghum species. The current study utilized 14 alien Sorghum species and established that pollen-pistil incompatibilities are the primary reasons that hybrids with sorghum are not obtained. The alien pollen tubes showed major inhibition of growth in sorghum pistils and seldom grew beyond the stigma. Pollen tubes of only three species grew into the ovary of sorghum. Fertilization and subsequent embryo development were not common. Seeds with developing embryos aborted before maturation, apparently because of breakdown of the endosperm. [ABSTRACT FROM AUTHOR]

The high new mutation rate and the wide spectrum of mutations found in patients with ornithine carbamoyltransferase (OCT) deficiency means that direct mutation analysis is essential for providing accurate carrier detection and prenatal diagnosis in affected families. We present our strategy for mutation detection in the OCT gene and summarize the results from 31 families with a confirmed diagnosis and 34 families with a suspected diagnosis of OCT deficiency, and describe 14 previously unreported mutations. [ABSTRACT FROM AUTHOR]

Important functions of water relations are considered to be related to genome size diversity in gymnosperms. We investigated relationships among genome size, dimensional characteristics of conductive cells, and water relations parameters by using young seedlings of six Pinus species. Xylem hydraulic conductivity was not correlated with genome size and dimensional characteristics of conductive cells, but the water potential at the turgor loss point was. Pinus species with large genome sizes had thick cell walls and small ratios of lumen radii to cell wall thickness in their conductive cells, and those species lost their turgor to tissue dehydration at low water potentials. The characteristics observed in the present study may contribute to pine drought tolerance. [ABSTRACT FROM AUTHOR]

Benign primary tumors of the facial nerve are frequently misdiagnosed because of variable and subtle clinical manifestations. Three such cases of facial nerve neuroma seen in the past 3 years will be presented. Difficulties in patient assessment including the lack of specificity for topographic testing, as well as the capricious behavior of the facial nerve in these patients will be discussed. The efficacy of diagnostic techniques presently available and in use including computerized tomography and electrodiagnostic studies will be discussed. Diagnosis of these tumors might generally be thought to be straightforward and easier with the advent of new diagnostic techniques, but this has, in fact, not been the case. Techniques for removal and repair will be presented. The combined approach utilizing the mastoid and middle fossa will be presented. [ABSTRACT FROM AUTHOR]

Objectives For the last 10 years there has been an epidemic of hepatitis C virus ( HCV) infection in men who have sex with men ( MSM) in Europe, North America and Australia. The majority of those infected are also HIV-positive and it is unclear to what extent HIV-negative MSM are also at increased risk of infection with HCV. This study provides the first examination of the association between HIV and hepatitis C serostatus in a sample of MSM recruited in community settings. Methods A total of 1121 participants completed a short questionnaire in 2008/2009 giving demographic and behavioural data, and donated a sample of oral fluid that was subsequently tested for antibodies to selected pathogens ( HIV, syphilis and HCV). Results The seroprevalence of hepatitis C antibody was 2.1% [95% confidence interval ( CI) 1.4-3.2%]. It was more common in those with HIV infection [7.7% (95% CI 4.2-12.9%) vs. 1.2% (95% CI 0.6-2.1%) in those without HIV infection; P < 0.001], those with a history of syphilis [12.2% (95% CI 4.6-24.8%) vs. 1.7% (95% CI 1.0-2.6%) in those without such a history; P < 0.001] and those who reported casual unprotected anal intercourse in the previous year [4.1% (95% CI 2.0-7.4%) vs. 1.2% (95% CI 0.5-2.2%) in those who did not report such intercourse; P = 0.01]. There was no relationship between hepatitis C antibody (anti- HCV) status and other demographic variables (age, ethnicity, employment status or education). Conclusions The seroprevalence of anti- HCV in HIV-negative MSM (1.2%) was higher, but not significantly higher, than that in the general population (0.67%). The prevalence was significantly higher in those infected with HIV or with previous syphilis infection and in those reporting unprotected anal intercourse. Our findings support current British Association for Sexual Health and HIV guidelines recommending the provision of selective HCV testing in MSM according to individual risk profile. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which focuses on the study aimed to determine if European physicians overestimate life expectancy and the impact of interventions in people with Type 2 diabetes.

Aim: To conduct an analysis to assess whether the completion of recommended diabetes care processes (glycated haemoglobin [HbA1c], creatinine, cholesterol, blood pressure, body mass index [BMI], smoking habit, urinary albumin, retinal and foot examinations) at least annually is associated with mortality., Materials and Methods: A cohort from the National Diabetes Audit of England and Wales comprising 179 105 people with type 1 and 1 397 790 people with type 2 diabetes, aged 17 to 99 years on January 1, 2009, diagnosed before January 1, 2009 and alive on April 1, 2013 was followed to December 31, 2019. Cox proportional hazards models adjusting for demographic characteristics, smoking, HbA1c, blood pressure, serum cholesterol, BMI, duration of diagnosis, estimated glomerular filtration rate, prior myocardial infarction, stroke, heart failure, respiratory disease and cancer, were used to investigate whether care processes recorded January 1, 2009 to March 31, 2010 were associated with subsequent mortality., Results: Over a mean follow-up of 7.5 and 7.0 years there were 26 915 and 388 093 deaths in people with type 1 and type 2 diabetes, respectively. Completion of five or fewer, compared to eight, care processes (retinal screening not included as data were not reliable) had a mortality hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.28-1.46) in people with type 1 and 1.32 (95% CI 1.30-1.35) in people with type 2 diabetes. The HR was higher for respiratory disease deaths and lower in South Asian ethnic groups., Conclusions: People with diabetes who have fewer routine care processes have higher mortality. Further research is required into whether different approaches to care might improve outcomes for this high-risk group., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To evaluate the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus comparator regimens for type 2 diabetes in Spain, based on real-world evidence., Materials and Methods: Clinical data were taken from the European Xultophy Treatment Retrospective Audit (EXTRA) real-world evidence study in which patients failing to meet glycaemic targets were switched to IDegLira. Baseline regimens (prior to IDegLira treatment) were categorized as: multiple daily insulin injections (MDI; 28%); glucagon-like peptide-1 (GLP-1) receptor agonists in combination with insulin (24%); basal insulin (19%); GLP-1 receptor agonists (10%); and non-injectable medications (19%). The IQVIA CORE Diabetes Model was used to project long-term outcomes for patients switching to IDegLira or continuing their baseline regimens (excluding non-injectable regimens). Costs were accounted from a Spanish National Health System perspective. Future costs and clinical benefits were discounted at 3% annually and sensitivity analyses were performed., Results: IDegLira was projected to reduce the incidence of diabetes-related complications and improve quality-adjusted life expectancy versus all four comparators. IDegLira reduced direct medical costs versus GLP-1 receptor agonists in combination with insulin, and versus GLP-1 receptor agonist therapy, and was therefore considered dominant (cost saving while improving outcomes). IDegLira was found to be cost-effective versus MDI and basal insulin with incremental cost-effectiveness ratios of EUR 3013 per quality-adjusted life-year (QALY) gained and EUR 6890 per QALY gained, respectively., Conclusions: Long-term projections based on real-world evidence indicated that IDegLira is likely to improve clinical outcomes and reduce costs or be cost-effective compared with other injectable regimens in people with type 2 diabetes in Spain., (© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To describe the real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide., Materials and Methods: This European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available., Results: Baseline regimens included non-injectable medications (19%), basal insulin (19%), GLP-1RA (10%), free combination therapy (insulin/GLP-1RA, 24%) and multiple daily-dose insulin injections (MDI, 28%), all ± oral antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c) reductions were observed in patients overall and in all subgroups (-10 mmol/mol [-0.9%] overall; P < .0001), and a significant reduction in mean body weight (-0.7 kg; P < .05) was observed in patients overall and in patients receiving MDI (-2.4 kg; P < .0001). The mean IDegLira dose was 22, 30 and 32 dose steps at initiation, and at 6 and 12 months follow-up, respectively. In total, only 67 patients reached the maximum 50 dose steps, with most coming from the free combination therapy (n = 31) or MDI (n = 15) baseline regimen groups. Hypoglycaemia rates were reduced by 82% (rate ratio 0.18; P < .0001) in the 6-month period after vs before IDegLira initiation. Overall, a total of 12 patients experienced 15 events in the 6 months after IDegLira initiation., Conclusion: In real-world practice, after 6 months and at a moderate dose, IDegLira resulted in substantial reductions in HbA1c and body weight, with a reduced risk of hypoglycaemia., (© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: Low serum levels of 25-hydroxyvitamin D (25[OH]D; vitamin D) are associated with a higher frequency of cardiovascular disease and risk factors in the general population. Vitamin D deficiency has also been noted in systemic lupus erythematosus (SLE). The objective of this study was to evaluate the associations of serum 25(OH)D levels with cardiovascular risk factors in women with SLE., Methods: Data collected in 181 women with SLE included demographics, SLE activity and damage assessments, cardiovascular risk factors, medications, and laboratory assessments of inflammatory markers and 25(OH)D levels. Multiple linear and logistic regressions were used to estimate the association of 25(OH)D levels with cardiovascular risk factors., Results: The mean age and disease duration were 43.2 and 11.9 years, respectively. The mean 25(OH)D level was 27.1 ng/ml and 62.2% had 25(OH)D levels <30 ng/ml. In unadjusted analyses, lower 25(OH)D levels were significantly associated with higher diastolic blood pressure, low-density lipoprotein cholesterol, lipoprotein(a), body mass index (BMI), and fibrinogen levels, as well as self-reported hypertension and diabetes mellitus. Lower 25(OH)D levels were also significantly associated with higher SLE disease activity and damage scores. After adjustment for age, seasonal variation, and race/ethnicity, lower 25(OH)D levels were also significantly related to higher fasting serum glucose. With further adjustment for BMI, associations between 25(OH)D and cardiovascular risk factors were no longer significant., Conclusion: This study demonstrates that vitamin D levels are low in women with SLE and significant associations exist with selected cardiovascular risk factors, although most of these associations can be explained by BMI.

This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia (FH) by finding a genetic mutation reduces patients' perceptions of control over the disease and adherence to risk-reducing behaviors. Three hundred forty-one families, comprising 341 hypercholesterolemia probands and 128 adult relatives, were randomized to one of two groups: (a) routine clinical diagnosis; (b) routine clinical diagnosis plus genetic testing (mutation searching in probands and direct gene testing in relatives). The main outcome measures were perceptions of control over hypercholesterolemia, adherence to cholesterol-lowering medication, diet, physical activity, and smoking. There was no support for the main hypothesis: finding a mutation had no impact on perceived control or adherence to risk-reducing behavior (all P-values > 0.10). While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack, participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level (P = 0.02 at 6 months) and showed a trend in believing more strongly in the efficacy of cholesterol-lowering medication (P = 0.06 at 6 months). In conclusion, finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk-reducing behaviors. The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition, but does affect their perceptions of how control is most effectively achieved. Further work is needed to determine whether similar results will be obtained in populations with little previous awareness of their risks., (Copyright 2004 Wiley-Liss, Inc.)

The correct positions of the deuterium (D) atoms of many of the bound waters in the protein concanavalin A are revealed by neutron Laue diffraction. The approach includes cases where these water D atoms show enough mobility to render them invisible even to ultra-high resolution synchrotron-radiation X-ray crystallography. The positions of the bound water H atoms calculated on the basis of chemical and energetic considerations are often incorrect. The D-atom positions for the water molecules in the Mn-, Ca- and sugar-binding sites of concanavalin A are described in detail.

Two clones, pCN1 and pCN2, which together form full-length cDNA for N-ras, were used to search for restriction fragment length polymorphisms. pCN2, which entirely consists of 3' non-translated sequences, revealed more bands on DNA transfer hybridizations than could be accounted for using the known restriction map of N-ras. None of the extra cross hybridizing sequences is located on chromosome 1. One of these sequences showed a high-frequency two-allele polymorphism with the restriction enzyme TaqI and maps to the short arm of chromosome 9. Of the remaining two sequences, one maps to chromosome 22 and the other maps to the short arm of chromosome 6. pCN1A, which contains the 5' untranslated regions and all the coding exons of N-ras only hybridized to the chromosome 1 site. No polymorphisms have been found for pCN1 with TaqI, MspI, BclI, BglI, EcoRI, BstXI, XbaI, BamHI, BglII or HindIII.

Nine families were examined for linkage on chromosome 1 between the hypervariable gene PUM and the alpha-spectrin (SPTA) gene using DNA probes. Close linkage was found with a maximum lod score of 5.98 at theta = 0.05. Hybridization to DNA from somatic cell hybrids made from a parent line carrying a balanced X:1 translocation showed both genes to lie proximal to the breakpoint at 1q23. DNA hybridization to cell lines carrying deletions of 1q21-25 showed the presence of two polymorphic alleles for both loci. These results, combined with existing in situ hybridization data, suggest PUM and SPTA both lie within 1q21. Linkage analysis between PUM and the Duffy blood group (FY) gave a maximum lod of 2.15 at theta = 0.15. These data combined with data from another laboratory give a maximum lod of 5.21 for linkage between PUM and FY at theta = 0.10.