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This chapter discusses the development and implementation of the Kansas Study of Instructional Costs and Productivity, which collects and reports data on community college instructional costs and faculty workloads. The project provides data for both intra- and inter-institutional comparisons about how much community college faculty teach and the cost of that instruction at the discipline level. (Contains 1 table.)

Population genetic studies can be useful for informing conservation and management. In Atlantic salmon, Salmo salar L., population structuring frequently occurs between river systems, but contrasting patterns occur within rivers, highlighting the need for catchment-specific studies to inform management. Here, population structure of Atlantic salmon was examined in the River Tamar, United Kingdom, using 12 microsatellite loci. Gene diversity and allelic richness ranged from 0.80 to 0.84 and from 8.96 to 10.24, respectively. Some evidence of genetic structure was found, including significant genetic differentiation between samples in different subcatchments (pairwise θ and tests of genic differentiation), results from assignment tests and a pattern of isolation by distance. Conversely, revealed only one population cluster, and an analysis of molecular variance showed no significant variation between subcatchments. Evidence of population bottlenecks depended on the mutation model assumed and is discussed with reference to catchment-specific studies of stock abundance. Implications for implementing management actions are considered. [ABSTRACT FROM AUTHOR]

Introduction: A large of amount of literature exists on the factors that influence the recruitment and retention of rural general practitioners (GPs) in Australia and other countries. The selection of a rural practice location is known to be influenced by professional, personal and family, community and economic factors. Most of this research has been undertaken on the either the baby boomer generation or their predecessors, and this is likely to have influenced the responses gained. Generation X and Y doctors are known to have a different perception regarding workload, lifestyle and the support required to practise. The aim of this study was to explore, from a Generation X perspective, factors deemed important by general practice graduates in selecting a rural practice at completion of their training. The study also aimed to identify the process general practice graduates use to identify a potential rural practice, and when they commence this process. Methods: Semi-structured interviews were held with 15 rural pathway general practice registrars in their final year of training with 2 regional training providers in South Australia. The interview topics included source of information on potential practices, their ideal rural practice and community, the process used to select a practice, and when they commenced this process. Phenomenological hermeneutic thematic analysis of interview transcripts was undertaken to identify themes and sub-themes. Results: For an ideal rural practice, registrars wished to work in a practice with a friendly atmosphere, good business structure, support from senior GPs and in close proximity to a hospital. They also wanted reasonable on-call arrangements, the chance to develop further skills (such as anaesthetics or obstetrics) and the freedom to practise according to their interests. They also emphasised the importance of a good team and an ethical practice. In terms of community, registrars wanted a positive living place, access to amenities such as childcare, good schools and the opportunity of work for their spouses. They also appreciated attractions such as the beach, or green farmland. Word of mouth, referrals by colleagues and experience of a practice were the most common approaches to finding a suitable rural practice. The majority of the registrars commenced selection of a rural practice in their last 6 months of training. Conclusions: Many of the factors identified by the Generation X registrars were similar to those identified by the previous generation. However, they also identified factors such as a positive team environment and practice with good ethics as important. The results can be used to tailor the marketing of rural practices to Generation X general practice registrars. [ABSTRACT FROM AUTHOR]

CDK (cyclin-dependent kinase) inhibitors have shown remarkable activity in CLL, where its efficacy has been linked to inhibition of the transcriptional CDKs (7 and 9) and deregulation of RNA polymerase and short-lived pro-survival proteins such as MCL1. Furthermore, ER (endoplasmic reticulum) stress has been implicated in CDK inhibition in CLL. Here we conducted a pre-clinical study of a novel orally active kinase inhibitor P1446A in CLL B-cells. P1446A inhibited CDKs at nanomolar concentrations and induced rapid apoptosis of CLL cells in vitro, irrespective of chromosomal abnormalities or IGHV mutational status. Apoptosis preceded inactivation of RNA polymerase, and was accompanied by phosphorylation of stress kinases JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase). Pharmacologic inhibitors of JNK/p38 MAPK conferred protection from P1446A-mediated apoptosis. Treatment with P1446A led to a dramatic induction of NOXA in a JNK-dependent manner, and sensitized CLL cells to ABT-737, a BH3-mimetic. We observed concurrent activation of apoptosis stress-inducing kinase 1 (ASK1) and its interaction with inositol-requiring enzyme 1 (IRE1) and tumor necrosis factor receptor-associated factor 2 (TRAF2) in CLL cells treated with P1446A, providing insights into upstream regulation of JNK in this setting. Consistent with previous reports on limited functionality of ER stress mechanism in CLL cells, treatment with P1446A failed to induce an extensive unfolded protein response. This study provides rationale for additional investigations of P1446A in CLL.

Abstract Background Alport syndrome (AS) is a progressive renal disease with cochlear and ocular involvement. The majority of AS cases are X-linked (XLAS) and due to mutations in the COL4A5 gene. Although the disease may appear early in life and progress to end stage renal disease (ESRD) in young adults, in other families ESRD occurs in middle age. Few of the more than four hundred mutations described in COL4A5 are associated with adult type XLAS, but the families may be very large. Methods We classified adult type AS mutation by prevalence in the US and we developed a molecular assay using a set of hybridization probes that identify the three most common adult type XLAS mutations; C1564S, L1649R, and R1677Q. Results The test was validated on samples previously determined to contain one or none of these mutations. In the US, the test's clinical specificity and sensitivity are estimated to be higher than 99% and 75% respectively. Analytical specificity and sensitivity are above 99%. Conclusion This test may be useful for presymptomatic and carrier testing in families with one of the mutations and in the diagnosis of unexplained hematuria or chronic kidney disease.

Background: Alport syndrome (AS) is a progressive renal disease with cochlear and ocular involvement. The majority of AS cases are X-linked (XLAS) and due to mutations in the COL4A5 gene. Although the disease may appear early in life and progress to end stage renal disease (ESRD) in young adults, in other families ESRD occurs in middle age. Few of the more than four hundred mutations described in COL4A5 are associated with adult type XLAS, but the families may be very large.Methods: We classified adult type AS mutation by prevalence in the US and we developed a molecular assay using a set of hybridization probes that identify the three most common adult type XLAS mutations; C1564S, L1649R, and R1677Q.Results: The test was validated on samples previously determined to contain one or none of these mutations. In the US, the test's clinical specificity and sensitivity are estimated to be higher than 99% and 75% respectively. Analytical specificity and sensitivity are above 99%.Conclusion: This test may be useful for presymptomatic and carrier testing in families with one of the mutations and in the diagnosis of unexplained hematuria or chronic kidney disease. [ABSTRACT FROM AUTHOR]

We describe humoral immune responses in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 Omicron variant infection. In dried blood spot (DBS) collected within 5 days of illness onset and during convalescence, we measured binding antibody (bAb) against ancestral spike protein receptor binding domain (RBD) and nucleocapsid (N) protein using a commercial multiplex bead assay. Geometric mean bAb concentrations against RBD increased by a factor of 2.5 from 1258 to 3189 units/mL and by a factor of 47 against N protein from 5.5 to 259 units/mL between acute illness and convalescence; lower concentrations were associated with greater geometric mean ratios. Paired DBS specimens may be used to evaluate humoral response to SARS-CoV-2 infection., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Objective: Describe available data on birth defects and pregnancy loss in women with systemic lupus erythematosus (SLE) exposed to belimumab., Methods: Data collected from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports up to 8 March 2020 were described. Belimumab exposure timing, concomitant medications and potential confounding factors were summarised descriptively., Results: Among 319 pregnancies with known outcomes (excluding elective terminations), 223 ended in live births from which birth defects were identified in 4/72 (5.6%) in belimumab-exposed pregnancies and 0/9 placebo-exposed pregnancies across 18 clinical trials, 10/46 (21.7%) belimumab-exposed pregnancies in the BPR prospective cohort (enrolled prior to pregnancy outcome) and 0/4 belimumab-exposed pregnancies in the BPR retrospective cohort (enrolled after pregnancy outcome), and 1/92 (1.1%) in belimumab-exposed pregnancies from postmarketing/spontaneous reports. There was no consistent pattern of birth defects across datasets. Out of pregnancies with known outcomes (excluding elective terminations), pregnancy loss occurred in 31.8% (35/110) of belimumab-exposed women and 43.8% (7/16) of placebo-exposed women in clinical trials; 4.2% (2/48) of women in the BPR prospective cohort and 50% (4/8) in the BPR retrospective cohort; and 31.4% (43/137) of belimumab-exposed women from postmarketing/spontaneous reports. All belimumab-exposed women in clinical trials and the BPR received concomitant medications and had confounding factors and/or missing data., Conclusions: Observations reported here add to limited data published on pregnancy outcomes following belimumab exposure. Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use., Competing Interests: Competing interests: KG, MKh, RAL, AL, RM, MBC, KW, JHNH, HQ, PJ and DAR are employees of GSK and hold shares in the company. KG is a previous employee of Novartis and holds shares in the company. At the time of the study, MKu, PM and JMP were employees of GSK and hold shares in the company. MP received grant support from GSK and is a member of the BPR Scientific Advisory Committee. HL received royalties/licences from UpToDate Inc (Wolters Kluwer Health), has received consulting fees from AMAG Pharmaceuticals and is a member of the BPR Scientific Advisory Committee. KS is employed by the University of North Carolina at Chapel Hill to assist GSK with research. HT is a member of the BPR Scientific Advisory Committee and a GSK retiree. MEBC received grants from GSK and UCB, and acted as a consultant to GSK and UCB. RAL is the guarantor., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Musculoskeletal pain is a common reason to seek outpatient physical therapy care. Generational differences regarding attitudes and beliefs have been found in many areas, but it has not been explored regarding pain., Objectives: This study aimed to examine generational differences in attitudes and beliefs regarding pain and the potential differences between beneficial and non-beneficial treatment options in patients receiving care in outpatient physical therapy clinics., Design: Cross-sectional descriptive survey., Method: A survey was developed to explore attitudes, beliefs, and treatment preferences. The survey was emailed out to past and current physical therapy patients as part of the customer satisfaction survey over a four-month period., Results/findings: 2260 surveys were completed during the collection period. Generational differences were found between the different generational groups. Younger generations were more in line with current pain neuroscience, understanding that pain is normal and part of the survival mechanism and less likely to believe that pain meant something wrong with one's tissues. Younger generations also reported more agreeance to the ability to cope without medication. However, significant variations existed in treatment choices that were most beneficial and least beneficial between respondents., Conclusion: Generational differences do exist in some areas of pain attitudes and beliefs. Less variation was noted in treatment options between generations, but there were significant variations within all patient respondents., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

On November 10, 2021, the Michigan Department of Health and Human Services (MDHHS) was notified of a rapid increase in influenza A(H3N2) cases by the University Health Service (UHS) at the University of Michigan in Ann Arbor. Because this outbreak represented some of the first substantial influenza activity during the COVID-19 pandemic, CDC, in collaboration with the university, MDHHS, and local partners conducted an investigation to characterize and help control the outbreak. Beginning August 1, 2021, persons with COVID-19-like* or influenza-like illness evaluated at UHS received testing for SARS-CoV-2, influenza, and respiratory syncytial viruses by rapid multiplex molecular assay. † During October 6-November 19, a total of 745 laboratory-confirmed influenza cases were identified. § Demographic information, genetic characterization of viruses, and influenza vaccination history data were reviewed. This activity was conducted consistent with applicable federal law and CDC policy. ¶ ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Emily T. Martin reports grants from Merck, outside the submitted work. Adam S. Lauring reports personal fees from Sanofi and personal fees from Roche, outside the submitted work. No other potential conflicts of interest were disclosed.

Background: Defining an intraoperative radiographic view to best determine the radial styloid screw position in locked volar plating of distal radius fractures may improve fixation and aid in decreasing cortical penetration and implant complication. We used a cadaveric model to demonstrate a reproducible, oblique radiographic view to identify the radial styloid screw position. Methods: Nine fresh-frozen elbow-to-fingertip cadavers were used for this study. A 2.4-mm variable angle volar distal radius locking plate was applied to the distal radius. A Kirschner wire (K-wire) was inserted into the radial styloid through the plate. Placement of the K-wire through the tip of the styloid at the cortical edge was confirmed through a separate radial incision. A second K-wire was placed through the radius shaft into the ulna to aid in angular measurements. Live fluoroscopic imaging was used as the forearm was brought from full 90° of supination toward neutral. Once the K-wire was abutting the cortical edge, rotation ceased, and a goniometer was used to measure the angle of forearm rotation. This was repeated for a total of 3 repetitions on each specimen. Results: The average angle of supination best depicting the position of the radial styloid screw was 68.5° (range = 64.3°-70.5°). Conclusions: Radial styloid screw fixation in locked volar plating of distal radius fractures increases the ultimate strength to failure, but screw penetration and tendon irritation can occur. The 70° supinated oblique intraoperative view provides the most accurate evaluation of the position of the radial styloid screw.

Background: Understanding risk factors for readmission may help decrease the rate of these costly events. The purpose of this study is to define the incidence of 30-day readmission and unscheduled health care contact (UHC) after distal radius fracture (DRF). In addition, we aim to define risk factors for readmission and UHC. Methods: A retrospective review of patients who sustained a DRF at our trauma center was performed. We recorded baseline demographics, fracture characteristics, and treatment. Any UHC or readmission (including emergency department [ED] visits) was documented. Reasons for readmission and UHC were stratified by cause. We utilized a case-control design comparing patients readmitted within 30 days after DRF versus those who were not, as well as patients with and without UHC. Results: About 353 patients were identified. The 30-day incidence of readmission after DRF was 7% with 2% of patients readmitted for reasons related to their fracture. Twenty percent of patients had UHC within 30 days, most frequently due to pain. Patients with anxiety or depression and those with open fractures were more likely to be readmitted. Patients with UHC were younger, more likely to have depression or anxiety, and more likely to have undergone operative treatment. Conclusions: For patients sustaining DRF, we report a 30-day readmission rate of 7% with 20% of patients having UHC. Patients with depression or anxiety were more likely to be both readmitted and have UHC. Identifying risk factors for readmission during initial presentation may help reduce readmissions. Improving pain relief strategies early may aid in decreasing the burden of UHC.

Background: Acute respiratory infections (ARIs) are the leading indication for antibacterial prescriptions despite a viral etiology in the majority of cases. The lack of available diagnostics to discriminate viral and bacterial etiologies contributes to this discordance. Recent efforts have focused on the host response as a source for novel diagnostic targets although none have explored the ability of host-derived microRNAs (miRNA) to discriminate between these etiologies. Methods: In this study, we compared host-derived miRNAs and mRNAs from human H3N2 influenza challenge subjects to those from patients with Streptococcus pneumoniae pneumonia. Sparse logistic regression models were used to generate miRNA signatures diagnostic of ARI etiologies. Generalized linear modeling of mRNAs to identify differentially expressed (DE) genes allowed analysis of potential miRNA:mRNA relationships. High likelihood miRNA:mRNA interactions were examined using binding target prediction and negative correlation to further explore potential changes in pathway regulation in response to infection. Results: The resultant miRNA signatures were highly accurate in discriminating ARI etiologies. Mean accuracy was 100% [88.8-100; 95% Confidence Interval (CI)] in discriminating the healthy state from S. pneumoniae pneumonia and 91.3% (72.0-98.9; 95% CI) in discriminating S. pneumoniae pneumonia from influenza infection. Subsequent differential mRNA gene expression analysis revealed alterations in regulatory networks consistent with known biology including immune cell activation and host response to viral infection. Negative correlation network analysis of miRNA:mRNA interactions revealed connections to pathways with known immunobiology such as interferon regulation and MAP kinase signaling. Conclusion: We have developed novel human host-response miRNA signatures for bacterial and viral ARI etiologies. miRNA host response signatures reveal accurate discrimination between S. pneumoniae pneumonia and influenza etiologies for ARI and integrated analyses of the host-pathogen interface are consistent with expected biology. These results highlight the differential miRNA host response to bacterial and viral etiologies of ARI, offering new opportunities to distinguish these entities.

Somatic PIK3CA mutations may relate to pathogenesis of isolated macrodactyly. We set up to test the association between PIK3CA mutations with isolated macrodactyly in order to establish a more accurate and molecular mechanism-based diagnosis and classification. DNA extracted from affected tissues in 12 individuals with isolated macrodactyly was tested for PIK3CA mutation using targeted Sanger DNA sequencing. Ten patients had macrodactyly in the foot and two in the hand. Nine of the 12 patients were found to carry a low-level, mosaic PIK3CA mutation. The mutations identified, p.His1047Arg, p.His1047Leu, p.Glu545Lys, and p.Glu542Lys, are codons frequently mutated in cancers. Among all tissues tested, adipose had the highest mutation detection rate, followed by nerve and skin. Our results indicate that a high proportion of isolated macrodactyly patients carry a pathogenic PIK3CA mutation. Affected adipose, nerve and skin tissues are ideal for PIK3CA mutation analysis.

We describe the cases of two children who both presented in infancy with recurrent severe pulmonary hypertensive crises. Exhaustive clinical work-up failed to identify an underlying aetiology. The patients had no clinical response to steroids, immunoglobulins, or pulmonary vasodilators. Post-mortem examination revealed extensive invasive pulmonary capillary haemangiomatosis. There was no evidence of pulmonary venous occlusive disease. Given the lethal nature of this condition, early consideration of referral to a lung transplant centre should be considered in selected patients.

We present a method in which noncontinuously binding (loop-out) primers are used to exclude regions of DNA that typically interfere with PCR amplification and/or analysis by Sanger sequencing. Several scenarios were tested using this design principle, including M13-tagged PCR primers, non-M13-tagged PCR primers, and sequencing primers. With this technique, a single oligonucleotide is designed in two segments that flank, but do not include, a short region of problematic DNA sequence. During PCR amplification or sequencing, the problematic region is looped-out from the primer binding site, where it does not interfere with the reaction. Using this method, we successfully excluded regions of up to 46 nucleotides. Loop-out primers were longer than traditional primers (27 to 40 nucleotides) and had higher melting temperatures. This method allows the use of a standardized PCR protocol throughout an assay, keeps the number of PCRs to a minimum, reduces the chance for laboratory error, and, above all, does not interrupt the clinical laboratory workflow., (Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Psychological therapies for psychosis are well evidenced; however, service user preferences for psychological treatment and trial participation have been little researched., Aims: To investigate preferences for psychological treatments for psychosis and trial participation decisions within a sample of people with experience of psychosis., Method: Hypothetical preferences were assessed in 90 individuals diagnosed with non-affective psychosis: (a) willingness/unwillingness to participate in a psychological therapy trial; (b) willingness/unwillingness to be randomised to treatment condition; (c) preference for mode of therapy; (d) reasons for preferences; (e) socio-demographic and clinical characteristics associated with preferences., Results: Most participants reported willingness to participate in a therapy trial and preferred not to be randomly allocated. Reasons for preferences were diverse, and preferences were not associated with socio-demographic or clinical variables., Conclusions: The need for treatment choice in services for psychosis and further research in this area has been highlighted.

Background and Purpose: To assess whether prophylactic postoperative intraaortic balloon counterpulsation (IABC) reduces the risk of poor outcome because of vasospasm following aneurysmal subarachnoid haemorrhage relative to conventional hypervolemic therapy (HT)., Methods: This was a single-center, parallel group randomized controlled trial. Patients suffering a subarachnoid hemorrhage at high risk of vasospasm were eligible. Patients were randomly allocated to receive prophylactic IABC (n=35) or HT (n=36). The primary end point was Glasgow Outcome and SF-36 scores assessed at 6 months by a blinded and independent observer and analyzed by intention to treat. Secondary analysis of physiological parameters was by treatment performed., Results: Twenty-seven patients in each arm had a good outcome (P=0.55). There was no statistical difference in mean SF-36 score (t=0.39, P=0.70). There were no long-term complications secondary to IABC. There were no differences in preload (pulmonary artery wedge pressure, P=0.97) or afterload (mean arterial pressure, P=0.97). IABC was associated with a lower cardiac output (P=0.002) and higher systemic vascular resistance (P=0.005), although for both groups mean cardiac output was >6 L/min. Cerebral blood flow was not different between groups: HT=41.5 (SD 7.2), IABP=44.9 (SD 8.6) mL/100 g/min (P=0.14)., Conclusions: In this study, prophylactic IABC did not improve perfusion indices or confer any clinical benefit following subarachnoid haemorrhage in patients with normal cardiac function. The study was small, however, and cannot be extrapolated to patients with cardiac failure and medically refractory symptomatic cerebral vasospasm. Clinical Trial Registration- This trial was not registered because enrolment began prior to July 1, 2005.

Hereditary hemochromatosis is an inherited disorder of iron metabolism, characterized by high absorption of iron by the gastrointestinal tract leading to a toxic accumulation of iron in various organs and impaired organ function. Three variants in the HFE gene (p.C282Y, p.H63D, and p.S65C) are commonly associated with the development of the disease. Of these, p.C282Y homozygotes are at the highest risk. Compound heterozygotes of p.C282Y along with p.H63D or p.S65C have reduced penetrance. Furthermore, p.H63D homozygotes are not at an increased risk and little is known about the risk associated with homozygocity for p.S65C. Our current clinical assay for the three common HFE variants utilizes the LightCycler platform and paired probes employing fluorescent resonance energy transfer. To increase throughput and decrease costs, we developed a method whereby automated extraction was combined with unlabeled probes and differential melt profiles to detect these variants using the LightCycler 480 instrument. Using this approach, 43 samples extracted with three different extraction platforms were correctly genotyped. These data demonstrate that the newly developed assay to genotype the HFE mutations p.C282Y, p.H63D, and p.S65C, combined with high-throughput extraction platforms, is accurate and reproducible and represents an alternative to previously described tests.

Legius syndrome (LS) is an autosomal dominant disorder caused by germline loss-of-function mutations in the sprouty-related, EVH1 domain containing 1 (SPRED1) gene. The phenotype of LS is multiple café au lait macules (CALM) with other commonly reported manifestations, including intertriginous freckling, lipomas, macrocephaly, and learning disabilities including ADHD and developmental delays. Since the earliest signs of LS and neurofibromatosis type 1 (NF1) syndrome are pigmentary findings, the two are indistinguishable and individuals with LS may meet the National Institutes of Health diagnostic criteria for NF1 syndrome. However, individuals are not known to have an increased risk for developing tumors (compared with NF1 patients). It is therefore important to fully characterize the phenotype differences between NF1 and LS because the prognoses of these two disorders differ greatly. We have developed a mutation database that characterizes the known variants in the SPRED1 gene in an effort to facilitate this process for testing and interpreting results. This database is free to the public and will be updated quarterly.

Deletions and duplications of single or multiple exons in specific genes are associated with human diseases. Multiplex ligation-dependant probe amplification (MLPA), a technique recently introduced to clinical laboratories, can detect deletions or duplications at the exon level. MLPA kits have a high multiplexing capability containing mixtures of exon-specific probes that target the gene of interest and control probes that hybridize to other genomic areas before PCR amplification. To verify each probe set, known positive samples with a single-exon deletion or duplication and normal samples are ideally used. Often, positive samples do not exist for each exon and normal samples are not suited to verify the identity of each probe set. We designed a straightforward approach using mixes of exon-specific PCR products as template to unequivocally verify each probe set in MLPA kits. This method can be used to verify the identity of MLPA probes for exons when positive samples are unavailable. Exon-specific probes from 15 MLPA kits were shown to hybridize to the targeted exons of interest. In one kit, this method identified probes that also bind a pseudogene, making them unreliable for clinical analysis. Incorporating this methodology in the analytical validation process will help ensure that MLPA results are interpreted correctly.

Objective: To explore the practice of delivering non-invasive ventilation (NIV) in non-designated areas within a large university teaching hospital by critical care outreach nurses., Methods: Local audit was prospectively conducted over a five-month period of all patients commenced on NIV in non-designated areas. The audit was repeated a year later and again four years later., Main Outcome Measures: Documentation of patient diagnosis and management plan including whether they were suitable for attempted cardiopulmonary resuscitation and endotracheal intubation as per British Thoracic Society guidelines (2002). Patient outcome (to hospital discharge) and arterial blood gas results pre and post commencement of NIV., Results: 115 patients received NIV for the treatment of acute respiratory failure. The mortality rate for the first 2 years data combined (n75) was 57% and attributed to the fact that patients were elderly, acidotic and had diagnoses associated with a poor response to NIV. 86% of patients had a documented resuscitation status and management plan. Resuscitation status (p=0.01) and arterial blood gas improvement within two hours of therapy had a significant effect on patient outcome (p=0.001). Four years later the mortality rate had reduced to 35% possibly due to appropriate patient selection. More patients were deemed suitable for resuscitation, were transferred to designated areas and electively ventilated., Conclusion: Inappropriate use of NIV in non-designated areas is associated with a high mortality. Critical care outreach nurses can play a pivotal role in influencing appropriate patient selection for NIV., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The Factor V Leiden mutation (FVL; c.1601G>A, p.Arg534Gln), the most common aberration underlying activated Protein C resistance, results in disruption of a major anticoagulation pathway and is a leading cause of inherited thrombophilia. A high-throughput assay for FVL mutation detection was developed using a single unlabeled probe on a high-resolution platform, the 96-well Roche 480 LightCycler (LC480) instrument. This method replaced the U.S. Food and Drug Administration-approved Roche Factor V Leiden kit assay on the LightCycler PCR instrument, decreasing total cost by 48%. The analytical sensitivity and specificity of the LC480 high-resolution assay approached 100% for the FVL mutation. Factor V mutations in proximity to the FVL locus may influence probe binding efficiency and melt characteristics. One out of three very rare variants tested in a separate study, 1600delC, was not distinguishable from FVL using the described high-resolution assay. However, a c.1598G>A variant, which changes the amino acid sequence from arginine to lysine at position 533, was detected by this high-resolution assay and confirmed by bidirectional sequencing. In the labeled probe LightCycler assay, the c.1598G>A variant was indistinguishable from the heterozygous FVL control. The c.1598G>A variant has not been described previously and its clinical significance is uncertain. In conclusion, the LC480 FVL assay is cost effective in a high-throughput setting, with capability to detect both previously described and novel FV variants.