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In 2015 the National Institute for Health and Care Excellence (NICE) updated its 2006 guideline to clarify the association between parent infant co-sleeping and sudden infant death syndrome (SIDS). The practice of co-sleeping is a topic of continuing controversy and debate. Rather than highlighting the risks, the emphasis of the NICE guideline is to provide parents with balanced information so that they can make informed decisions about where their babies sleep. This contradicts previous public health messages on co-sleeping that discourages parents from the practice. Consequently, the updated national guideline has been criticised for failing to provide parents with safer sleep information, which has led to widespread confusion for parents and professionals. Health professionals can deliver safer sleep advice to support parents in their decision-making. However, as a result of inconsistent guidelines and evidence about parent-infant co-sleeping, health professionals may feel apprehensive and ill-equipped to provide advice and support. This article draws on a non-exhaustive literature review to discuss the risks and benefits of parent-infant co-sleeping, and the implications of this practice for SIDS. It also aims to provide transparency and improve understanding for health professionals so that they can support parents to adopt safer sleep strategies for their baby.

We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.

Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5 and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish. Zebrafish prps1a mutants and prps1a;prps1b double mutants showed similar morphological phenotypes with increasingly severe phenotypes as the number of mutant alleles increased. Phenotypes included smaller eyes and reduced hair cell numbers, consistent with the optic atrophy and hearing impairment observed in human patients. The double mutant also showed abnormal development of primary motor neurons, hair cell innervation and reduced leukocytes, consistent with the neuropathy and recurrent infection of the human patients possessing the most severe reductions of PRPS1 activity. Further analyses indicated the phenotypes were associated with a prolonged cell cycle likely resulting from reduced nucleotide synthesis and energy production in the mutant embryos. We further demonstrated the phenotypes were caused by delays in the tissues most highly expressing the prps1 genes.

The Atlanta Regional Commission and the Atlanta Housing Authority are working together to address the unique challenges and opportunities of naturally occurring retirement communities. Leveraging local partnerships and several converging initiatives, a multidisciplinary team is developing and coordinating resources and supports while re-imagining the physical structure of affordable public housing communities for the elderly and individuals with disabilities. This article will examine how the application of the Atlanta Regional Commission's Lifelong Community framework in one high-rise apartment building, Marian Road, has broadened supports for aging residents while changing the way the Atlanta Regional Commission and the Atlanta Housing Authority serve the needs of current and future older adults. However, it is clear that replication on any significant scale will require a shift in federal and state rules that regulate housing construction, housing subsidies, and community-based services that only margi...

A programme of archaeological assessment, funded through the Aggregates Levy Sustainability Fund, was undertaken at the Valdoe Quarry in West Sussex ahead of a renewed and final stage of gravel extraction at the site. This paper gives an account of the evidence for human activity recovered in the course of this work. The analysis demonstrates that the Valdoe Quarry contained archaeology relating to the transport and modification of bifaces. These signatures formed part of wider patterns of land-use operated by the same hominin groups found at Boxgrove, within a single, developing palaeolandscape. It is concluded that further activity sites remain to be discovered within the general environs of the Valdoe and the parish of East Lavant where historically there have been surface finds of bifaces.

Introduction and aim Post-percutaneous coronary intervention (PCI) length of hospital stay (LOHS) is one of the key modifiers of hospital cost and quality assessment. Commencing 2000, the cardiovascular services at our institution engaged in a continuous quality improvement program to reduce post-PCI LOHS. Methods All PCI patients were screened for potential early discharge. An expedited discharge protocol was applied to all suitable patients. Length of hospital stay and other outcomes were monitored daily. Data were compiled and reported monthly and quarterly by an independent chart review and data analysis team. Results Over the study period, PCI volume increased 4-fold. Annually, 61.8% to 78.4% of the patients were rendered suitable for abbreviated LOHS. Timely discharge of suitable candidates gradually improved from 77.6% (n = 116) discharged within 48 hours in 2000 to 95% (n = 480) discharged within 30 hours in 2006. Conclusion With the appropriate continuous quality improvement program, 30-hour post-PCI discharge is feasible in more than 95% of suitable cases.

The gamma-actin gene (ACTG1) encodes a major cytoskeletal protein of the sensory hair cells of the cochlea. Recently, mutations in ACTG1 were found to cause autosomal dominant, progressive, sensorineural hearing impairment linked to the DFNA20/26 locus on chromosome 17q25.3 in four American families and in one Dutch family. We report here the linkage of autosomal dominant, progressive, sensorineural hearing impairment in a large Norwegian family to the DFNA20/26 locus. Sequencing of ACTG1 identified a novel missense mutation (c.1109TC; p.V370A) segregating with the hearing loss. Functional analysis in yeast showed that the p.V370A mutation restricts cell growth at elevated temperature or under hyperosmolar stress. Molecular modelling suggested that the p.V370A mutation modestly alters a site for protein-protein interaction in gamma-actin and thereby modestly alters gamma-actin-based cytoskeletal structures. Nineteen Norwegian and Danish families with autosomal, dominant hearing impairment were analyzed for mutations in ACTG1 by sequencing, but no disease-associated mutations were identified. Finally, a long-term follow-up of the hearing loss progression associated with the p.V370A mutation in ACTG1 is provided. The present study expands our understanding of the genotype-phenotype relationship of this deafness gene and provides a sensitive and simple functional assay for missense mutations in this gene, which may assist future molecular diagnosis of autosomal-dominant hearing impairment. Finally, the present results do not indicate that mutations in ACTG1 are a frequent cause of autosomal-dominant postlingual sensorineural hearing impairment in Norway nor Denmark.

Background To date, it is unknown whether fexofenadine mitigates the worsening of symptoms induced by the cat allergen Felis domesticus allergen 1. Objective To determine the effects of a single dose of fexofenadine hydrochloride, 180 mg, in preventing and controlling cat allergen-induced allergic rhinitis symptoms using the cat room challenge model. Methods This single-center, randomized, double-blind, placebo-controlled, 2-way crossover study consisted of a screening visit, 1 or 2 qualifying visits, and 2 treatment periods separated by a mean ± SD washout period of 14 ± 3 days. Patients were randomized to treatment sequence 1 (placebo followed by fexofenadine) or sequence 2 (fexofenadine followed by placebo). Baseline end points were obtained before study drug administration, and allergen challenges were initiated 1½ hours after dosing. The primary end point was the change from predose baseline in the total symptom score (sum of rhinorrhea, itchy nose/palate/throat, sneezing, and itchy/watery/red eyes) after 30 minutes of allergen exposure compared with placebo. Results Of 211 patients screened, 66 were randomized and 63 completed the study. Mean change in the total symptom score from predose baseline was significantly less with fexofenadine compared with placebo 30 minutes after initiation of the cat allergen challenge (2 hours after dosing) ( P = .03). The overall incidence of treatment-emergent adverse events was low and comparable for both groups. Conclusion Prophylactic treatment with a single dose of fexofenadine hydrochloride, 180 mg, significantly mitigated the worsening of allergic rhinitis symptoms induced by exposure to cat allergen compared with placebo use.

Background: Prostate cancer represents a substantial public health burden worldwide. It is the second leading cause of cancer death among men in the United States. A family history of the disease is among the most well-established risk factors for prostate cancer. Efforts to localize prostate can cer susceptibility alleles by using genetic linkage analysis methods have been hindered by genetic heterogeneity, incomplete penetrance, disease phenocopies, and the lack of DNA samples from parents of individuals with late-onset prostate cancer. Methods: We performed a combined genome-wide linkage analysis among 426 families from four existing hereditary prostate cancer (HPC) study population to systematically search for prostate cancer susceptibility genes. To decrease the degree of locus heterogeneity, we analyzed subsets of families with similar clinical and demographic characteristics. Nonparametric multipoint linkage was the primary method of analysis. Results are presented as allele-sharing logarithm of the odds (LOD) scores, and all reported P values are two-sided. Results: The strongest evidence for prostate cancer linkage was found at chromosome region 17q22 (nonparametric multipoint Kong and Cox allele-sharing LOD score = 3.16 at marker D17S787; P = .00007). Stratified analyses revealed several additional chromosomal regions that are likely to segregate prostate cancer susceptibility genes among specific subsets of HPC families, including 15q11 among families with late-onset disease (allele-sharing LOD = 5.57 at marker D15S128; P

Genome-wide scan of Swedish families with hereditary prostate cancer : suggestive evidence of linkage at 5q11.2 and 19p13.3

BACKGROUND In order to identify predisposition loci to hereditary prostate cancer (HPC), we performed a genome-wide linkage analysis using samples from a genetically homogeneous population, with 13 Finnish multiplex prostate cancer families. METHODS Altogether 87 DNA samples were genotyped from 13 families. Logarithm-of-odds (LOD) scores were calculated for all autosomes using FASTLINK and GENEHUNTER designating all unaffected men and all women as unknown. RESULTS The highest LOD scores in the affected-only analyses were found at 11q14, where the two-point LOD score was 2.97 (θ = 0.0 at D11S901), GENEHUNTER heterogeneity LOD (HLOD) of 3.36, and a non-parametric-linkage (NPL) score of 2.67 (P = 0.008). A second positive site was at 3p25-26, with a two-point LOD score of 2.57 (θ = 0.01 at D3S1297), HLOD of 2.15, and NPL score of 2.27 (P = 0.02). CONCLUSIONS The results suggest two HPC regions in the Finnish population, which have not been reported previously and warrant further study. Prostate 57: 280–289, 2003. © 2003 Wiley-Liss, Inc.

BACKGROUND Previous linkage studies have suggested prostate cancer susceptibility genes located on chromosomes 1, 20, and X. Several putative prostate cancer candidate genes have also been identified including RNASEL, MSR1, and ELAC2. Presently, these linkage regions and candidate genes appear to explain only a small proportion of hereditary prostate cancer cases suggesting the need for additional whole genome analyses. METHODS A genome-wide mode-of-inheritance-free linkage scan, using 405 genetic markers, was conducted on 175 pedigrees, the majority containing three or more affected individuals diagnosed with prostate cancer. Stratified linkage analyses were performed based on previously established criteria. RESULTS Results based on the entire set of 175 pedigrees showed strong suggestive evidence for linkage on chromosome 17q (LOD = 2.36), with strongest evidence coming from the subset of pedigrees with four or more affected individuals (LOD = 3.27). Race specific analyses revealed strong suggestive evidence for linkage in our African-American pedigrees on chromosome 22q (LOD = 2.35). CONCLUSIONS Genome-wide analysis of a large set of prostate cancer families indicates new areas of the genome that may harbor prostate cancer susceptibility genes. Specifically, our linkage results suggest that there is a prostate cancer susceptibility gene on chromosome 17 that is independent of ELAC2. Further research including combined analyses of independent genome-wide scan data may clarify the most important regions for future investigation. Prostate 57: 326–334, 2003. Published 2003 Wiley-Liss, Inc.

BACKGROUND Although the subject of intensive study, the genetic influences responsible for familial clustering of prostate cancer remain largely unidentified. Genome-wide scans for linkage in prostate cancer families can be used to systematically search for genes capable of affecting risk for the disease. METHODS All available family members from 188 families, each having at least three first-degree relatives affected with prostate cancer, were genotyped at 406 markers distributed across the genome at average intervals of less than 10 cM. Genotype data was analyzed using primarily a non-parametric, multipoint approach, although parametric analyses were performed as well. RESULTS The strongest evidence for linkage was observed at D4S1615, at 4q21 (LOD of 2.8, P = 0.0002). Two other regions had LOD scores over 2.0: at 9q34 (marker D9S1826, LOD = 2.17, P = 0.0008) and at 2q23 (marker D2S151, LOD = 2.03, P = 0.001). An additional 12 regions had LOD scores over 1.0, including markers at 1q24-25 and 7q22 having scores >1.6. Stratifying the linkage results by age of diagnosis indicated that the linkages to chromosomes 2 and 4 were strongest in families with early and late ages of diagnosis, respectively. CONCLUSIONS Our data implicate several new loci as harboring prostate cancer susceptibility genes, and provide confirmatory evidence of linkage at several loci identified previously in other genome-wide scans, including the three regions (4q21, 9q34, and 2q23) with strongest evidence for prostate cancer linkage. These data also emphasize the need to combine linkage data from large numbers of prostate cancer families in efforts to effectively address the extensive heterogeneity that characterizes genetic aspects of this disease. Prostate 57: 320–325, 2003. © 2003 Wiley-Liss, Inc.

Over the past 20 years, the incidence of cutaneous malignant melanoma (CMM) has increased dramatically worldwide. A positive family history of the disease is among the most established risk factors for CMM; it is estimated that 10% of CMM cases result from an inherited predisposition. Although mutations in two genes, CDKN2A and CDK4, have been shown to confer an increased risk of CMM, they account for only 20%-25% of families with multiple cases of CMM. Therefore, to localize additional loci involved in melanoma susceptibility, we have performed a genomewide scan for linkage in 49 Australian pedigrees containing at least three CMM cases, in which CDKN2A and CDK4 involvement has been excluded. The highest two-point parametric LOD score (1.82; recombination fraction [theta] 0.2) was obtained at D1S2726, which maps to the short arm of chromosome 1 (1p22). A parametric LOD score of 4.65 (theta=0) and a nonparametric LOD score of 4.19 were found at D1S2779 in nine families selected for early age at onset. Additional typing yielded seven adjacent markers with LOD scores3 in this subset, with the highest parametric LOD score, 4.95 (theta=0) (nonparametric LOD score 5.37), at D1S2776. Analysis of 33 additional multiplex families with CMM from several continents provided further evidence for linkage to the 1p22 region, again strongest in families with the earliest mean age at diagnosis. A nonparametric ordered sequential analysis was used, based on the average age at diagnosis in each family. The highest LOD score, 6.43, was obtained at D1S2779 and occurred when the 15 families with the earliest ages at onset were included. These data provide significant evidence of a novel susceptibility gene for CMM located within chromosome band 1p22.

Background & Aims Small intestinal carcinoids are rare and difficult to diagnose and patients often present with advanced incurable disease. Although the disease occurs sporadically, there have been reports of family clusters. Hereditary small intestinal carcinoid has not been recognized and genetic factors have not been identified. We performed a genetic analysis of families with small intestinal carcinoids to establish a hereditary basis and find genes that might cause this cancer. Methods We performed a prospective study of 33 families with at least 2 cases of small intestinal carcinoids. Affected members were characterized clinically and asymptomatic relatives were screened and underwent exploratory laparotomy for suspected tumors. Disease-associated mutations were sought using linkage analysis, whole-exome sequencing, and copy number analyses of germline and tumor DNA collected from members of a single large family. We assessed expression of mutant protein, protein activity, and regulation of apoptosis and senescence in lymphoblasts derived from the cases. Results Familial and sporadic carcinoids are clinically indistinguishable except for the multiple synchronous primary tumors observed in most familial cases. Nearly 34% of asymptomatic relatives older than age 50 were found to have occult tumors; the tumors were cleared surgically from 87% of these individuals (20 of 23). Linkage analysis and whole-exome sequencing identified a germline 4-bp deletion in the gene inositol polyphosphate multikinase ( IPMK ), which truncates the protein. This mutation was detected in all 11 individuals with small intestinal carcinoids and in 17 of 35 family members whose carcinoid status was unknown. Mutant IPMK had reduced kinase activity and nuclear localization, compared with the full-length protein. This reduced activation of p53 and increased cell survival. Conclusions We found that small intestinal carcinoids can occur as an inherited autosomal-dominant disease. The familial form is characterized by multiple synchronous primary tumors, which might account for 22%–35% of cases previously considered sporadic. Relatives of patients with familial carcinoids should be screened to detect curable early stage disease. IPMK haploinsufficiency promotes carcinoid tumorigenesis.

Objective: Air medical transport (AMT) teams play an essential role in the care of the critically ill and injured. Their work, however, is not without risk. Since the inception of the industry numerous AMT accidents have been reported. The objective of this research is to gain a better understanding of the post-accident sequelae for professionals who have survived AMT accidents. The hope is that this understanding will empower the industry to better support survivors and plan for the contingencies of post-accident recovery. Methods: Qualitative methods were used to explore the experience of flight crew members who have survived an AMT accident. "Accident" was defined using criteria established by the National Transportation Safety Board. Traditional focus group methodology explored the survivors' experiences following the accident. Results: Seven survivors participated in the focus group. Content analysis revealed themes in four major domains that described the experience of survivors: Physical, Psychological, Relational and Financial. Across the themes survivors reported that industry and company response varied greatly, ranging from generous support, understanding and action to make safety improvements, to little response or action and lack of attention to survivor needs. Conclusion: Planning for AMT post-accident response was identified to be lacking in scope and quality. More focused efforts are needed to assist and support the survivors as they regain both their personal and professional lives following the accident. This planning should include all stakeholders in safe transport; the individual crewmember, air medical transport companies, and the industry at large.

Examined self-reported depressive symptoms in 72 young people with spina bifida, ages 9 to 18:11, and matched able-bodied comparison subjects, using the Dimensions of Depression Profile for Children and Adolescents (Harter & Nowakowski, 1987). Independent variables included gender, self-perceptions (including physical appearance), and perceived social support. Young people with spina bifida were at greater risk of depressive mood, low self-worth, and suicidal ideation. Girls, independent of disability, were at greater risk of depressive mood, low self-worth, and self-blame. Multiple regression analyses suggest that global self-worth serves as a mediating variable for the effect of physical appearance self-concept on depressed mood (particularly in young people with spina bifida), and that perceived parental social support has a direct effect on depressed mood (particularly in girls).

Autosomal recessive ataxias represent genetic and clinical heterogeneity. Unsteady gait is often accompanied by poor coordination of limbs, speech, and eye movements. To date, seven genes have been identified. In addition, five chromosomal loci have been localized in non-related families. Here, we report homozygosity mapping of a novel locus to a 19.5-cM region on chromosome 20q11-q13 in a large inbred Norwegian family with infantile non-progressive ataxia.

International audience; Smith-Magenis syndrome (SMS) is a disorder characterized by multiple congenital anomalies and behavior problems, including abnormal sleep patterns. It is most commonly due to a 3.5 Mb interstitial deletion of chromosome 17 band p11.2. Secretion of melatonin, a hormone produced by the pineal gland, is the body's signal for nighttime darkness. Published reports of 24-hr melatonin secretion patterns in two independent SMS cohorts (US and France) document an inverted endogenous melatonin pattern in virtually all cases (96%), suggesting that this finding is pathognomic for the syndrome. We report on a woman with SMS due to an atypical large proximal deletion ( approximately 6Mb; cenTNFRSFproteinB) of chromosome band (17)(p11.2p11.2) who presents with typical sleep disturbances but a normal pattern of melatonin secretion. We further describe a melatonin light suppression test in this patient. This is the second reported patient with a normal endogenous melatonin rhythm in SMS associated with an atypical large deletion. These two patients are significant because they suggest that the sleep disturbances in SMS cannot be solely attributed to the abnormal diurnal melatonin secretion versus the normal nocturnal pattern.

In most Dutch melanoma families, a founder deletion in the melanoma susceptibility gene CDKN2A (which encodes p16) is present. This founder deletion (p16-Leiden) accounts for a significant proportion of the increased melanoma risk. However, it does not account for the Atypical Nevus (AN) phenotype that segregates in both p16-Leiden carriers and non-carriers. The AN-affected p16-Leiden family members are therefore a unique valuable resource for unraveling the genetic etiology of the AN phenotype, which is considered both a risk factor and a precursor lesion for melanoma. In this study, we performed a genome-wide scan for linkage in four p16-Leiden melanoma pedigrees, classifying family members with five or more AN as affected. The strongest evidence for an atypical nevus susceptibility gene was mapped to chromosome band 7q21.3 (two-point LOD score=2.751), a region containing candidate gene CDK6.

We describe a pulsed green and ultraviolet laser source based on a frequency converted photonic crystal fiber (PCF) amplifier. The flexible-format all-fiber polarization maintaining (PM) seed source consists of cascaded ytterbium doped amplifiers seeded by a directly modulated 1064 nm laser diode. The seed generates pulses fixed at 3.5 ns duration from 20 kHz to 10 MHz. Up to 2.9 W of 532 nm (green) and 1 W of 355 nm (UV) output were obtained in tests from 20-100 kHz using LBO crystals for both the doubling and tripling conversion process. Scaling the pulse energies demonstrated at low repetition rates, to the high repetition rate operation possible with the flexible format seed source, shows the potential for high power, high repetition rate pulsed green and UV output for advanced applications.

We demonstrate passive phasing in a four channel high power passively phase-locked Yb fiber laser array. We achieved an output power of 710W with high fringe visibility from an array of LMA Yb fiber lasers.

BACKGROUND The African American Hereditary Prostate Cancer (AAHPC) Study was designed to recruit families with early-onset disease fulfilling criteria of ≥4 affected. METHODS We present a ∼10 cM genome-wide linkage (GWL) analysis on 77 families including 254 affected and 274 unaffected genotyped. RESULTS Linkage analysis revealed three chromosomal regions with GENEHUNTER multipoint HLOD scores ≥1.3 for all 77 families at 11q22, 17p11, and Xq21. One family yielded genome-wide significant evidence of linkage (LOD = 3.5) to the 17p11 region with seven other families ≥2.3 in this region. Twenty-nine families with no-male-to-male (MM) transmission gave a peak HLOD of 1.62 (α = 0.33) at the Xq21 locus. Two novel peaks ≥0.91 for the 16 families with ‘>6 affected’ occurred at 2p21 and 22q12. CONCLUSIONS These chromosomal regions in the genome warrant further follow-up based on the hypothesis of multiple susceptibility genes with modest effects, or several major genes segregating in small subsets of families. Prostate 67:22–31, 2007. © 2006 Wiley-Liss, Inc.

Background In contrast to gene-mapping studies of simple Mendelian disorders, genetic analyses of complex traits are far more challenging, and high quality data management systems are often critical to the success of these projects. To minimize the difficulties inherent in complex trait studies, we have developed GeneLink, a Web-accessible, password-protected Sybase database. Results GeneLink is a powerful tool for complex trait mapping, enabling genotypic data to be easily merged with pedigree and extensive phenotypic data. Specifically designed to facilitate large-scale (multi-center) genetic linkage or association studies, GeneLink securely and efficiently handles large amounts of data and provides additional features to facilitate data analysis by existing software packages and quality control. These include the ability to download chromosome-specific data files containing marker data in map order in various formats appropriate for downstream analyses (e.g., GAS and LINKAGE). Furthermore, an unlimited number of phenotypes (either qualitative or quantitative) can be stored and analyzed. Finally, GeneLink generates several quality assurance reports, including genotyping success rates of specified DNA samples or success and heterozygosity rates for specified markers. Conclusions GeneLink has already proven an invaluable tool for complex trait mapping studies and is discussed primarily in the context of our large, multi-center study of hereditary prostate cancer (HPC). GeneLink is freely available at http://research.nhgri.nih.gov/genelink.

In a recent genome-wide linkage (GWL) analysis of Finnish families at high risk for prostate cancer, we found two novel putative susceptibility loci at 3p25-p26 and 11q14. Here, we report the fine-mapping of these two critical regions at high resolution with 39 microsatellite markers in 16 families, including multiplex families that were not used in the GWL scan. The maximum multipoint HLOD was 3.39 at 3p26 and 1.42 at 11q14. The highest LOD scores were seen around markers D3S1270 and D3S4559 (α=0.89), covering approximately two megabases. The two known genes in this region CHL1 (cell adhesion molecule with homology to L1CAM) and CNTN6 (contactin 6) were screened for exonic mutations in the families showing the strongest linkage, but no disease-segregating sequence variants were observed. The recombination map pointed to a region proximal to the area of best linkage, suggesting that more genes may need to be investigated as candidates. These results provide strong evidence for the existence of a prostate cancer susceptibility gene at 3p26 in Finnish prostate cancer families. This locus has not been strongly linked with hereditary prostate cancer in other populations. However, the mildly positive 3p LOD scores in a recent GWL analysis of patients from the United States suggest that the locus may also be important in other populations.

Forensic and clinical laboratories benefit from DNA standard reference materials (SRMs) that provide the quality control and assurance that their results from sequencing unknown samples are correct. Therefore, the mitochondrial DNA (mtDNA) genome of HL-60, a promyelocytic leukemia cell line, has been completely sequenced by four laboratories and will be available to the forensic and medical communities in the spring of 2003; it will be called National Institute of Standards and Technology (NIST) SRM 2392-I. NIST human mtDNA SRM 2392 will continue to be available and includes the DNA from two apparently healthy individuals. Both SRM 2392 and 2392-I contain all the information (e.g. the sequences of 58 unique primer sets) needed to use these SRMs as positive controls for the amplification and sequencing any DNA. Compared to the templates in SRM 2392, the HL-60 mtDNA in SRM 2392-I has two tRNA differences and more polymorphisms resulting in amino acid changes. Four of these HL-60 mtDNA polymorphisms have been associated with Leber Hereditary Optic Neuropathy (LHON), one as an intermediate mutation and three as secondary mutations. The mtDNA from a cell line (GM10742A) from an individual with LHON was also completely sequenced for comparison and contained some of the same LHON mutations. The combination of these particular LHON associated mutations is also found in phylogenetic haplogroup J and its subset, J2, and may only be indicative that HL-60 belongs to haplogroup J, one of nine haplogroups that characterize Caucasian individuals of European descent or may mean that haplogroup J is more prone to LHON. Both these mtDNA SRMs will provide enhanced quality control in forensic identification, medical diagnosis, and single nucleotide polymorphism detection.

Currently in Great Britain 12.9% of the workforce are unemployed — over three million people. Within this overall total there are considerable variations in the levels of employment in different parts of the country. Even within individual local authorities there will be sizeable differences in the actual size of unemployment from one town to another.

The contractile properties of single rat cardiac myocytes isolated from normal and hypertrophied right ventricles have been investigated and then correlated with the isoenzyme pattern of ventricular myosin. The isoprenaline-stimulated contraction and the beta-adrenoceptor sensitivity were also investigated. Right ventricle hypertrophy was obtained by injecting monocrotaline, an alkaloid which induces severe pulmonary hypertension. The contractile parameters, namely contraction amplitude and speed of shortening, were obtained by means of an inverted microscope TV-system and edge-detection-device. Hypertrophied cells showed a significantly decreased speed of shortening and contraction amplitude when contraction was induced by maximum calcium and maximum isoprenaline. A statistically significant correlation existed between myosin alpha-chain percentage and both contraction parameters. Isoprenaline sensitivity expressed in terms of ED50, p kappa a and Hill coefficient were similar in the control and monocrotaline treated animals. Moreover no correlation between the degree of ventricular hypertrophy and ED50 existed. These results suggest that, in this animal model, the depressed contractile function which characterizes the hypertrophic myocardium depends on changes in isomyosin pattern while beta-adrenoceptor desensitization does not occur.

I just had a nervous tick. I was messy. I wasn't taking care of myself. That's why I just had to let it go. I had to get to the point that it's not that I didn't care, I just had to stop caring about being the best. Just let it go.--Augusta (1) Augusta's words provide a glimpse of her response to the realities of the classroom in her first days as a teacher. Augusta was a paid-intern completing her accelerated Masters of Arts in Teaching (M.A.T) degree while also beginning her first year teaching. During the course of her internship semester, her university supervisor, Lila, sought out the University Coordinator of Field Experiences to voice concerns about Augusta's transition to teaching. While Lila's other interns were experiencing a reasonably smooth transition into the classroom, Augusta seemed to be having an extremely difficult time. Lila expressed concerns about Augusta's severe anxiety; emotional distress, (i.e., crying); lack of self-care, (i.e., not eating and/or sleeping); and a desire to quit teaching. While some of these challenges are common to first year teachers (Chang, 2009; Fimian & Blanton, 1987; Kyriacou, 2011) it was the severity of Augusta's issues that alarmed Lila. The Field Experience Coordinator heard similar concerns from several university supervisors; she investigated and discovered the interns had been placed at different schools, at different grade levels, and had different university supervisors, yet each of them were reporting similar issues and all of them were part of the same cohort of M.A.T. students. The Field Experience Coordinator realized something unusual was occurring with this cohort and convened a meeting of the university supervisors involved to discuss if further investigation was warranted; we agreed the intensity of the emotional challenges expressed by the paidinterns justified further investigation. To understand the phenomena fully so that it may be corrected and prevented in the future, we conducted a phenomenological case study with Augusta and her cohort. The authors of this study represent the research team that was formed to initiate the inquiry, which includes the Field Experience Coordinator, the University Supervisors, a professor, and an additional doctoral student. Together, we endeavored collaboratively to examine the concerns of the cohort in response to what we identified as a problem of practice. From our perspectives and collective experience, we recognized that in order to support these non-traditional students, we needed a better understanding of the nature of their concerns. After obtaining IRB approval, our initial investigation revealed Augusta's concerns seemed to be rooted in her expectations of teaching. We wondered if her expectations could be considered typical (whatever that was), and if not, why? We suspected her expectations might be behind some of the difficulties and concerns she was experiencing. The following questions guided our investigation: 1) What are the expectations about teaching of a student in an accelerated M.A.T. program who is also a first-year teacher completing a paid internship? 2) In what ways are those expectations addressed? Alternative Teacher Preparation Programs To meet the demands for new teachers, alternative certification programs, such as accelerated MAT programs, are often designed to attract talented content specialists to the profession (Cooperman, 2000; Tigchelaar, 2010; Zumwalt, 1996). Alternative certification programs have similar standards and methods as traditional college and university programs, but they may have differing characteristics, such as, accelerated time frames for completion and reduced credit requirements and admission standards (Darling-Hammond, 1990). The perceived problems of traditionally prepared beginning teachers in their years are well documented and include problems with classroom discipline, motivating students, dealing with individual differences, assessing students' work, relationships with parents, organization of class work, and insufficient or inadequate teaching materials and supplies (Brindley & Parker, 2010; Good et al. …