Search

Purpose: The purpose of this study was to assess the association between speech sound articulation and childhood stuttering in a relatively large sample of preschool-age children who do and do not stutter, using the Goldman-Fristoe Test of Articulation-2 (GFTA-2; Goldman & Fristoe, 2000)., Method: Participants included 277 preschool-age children who do (CWS; n=128, 101 males) and do not stutter (CWNS; n=149, 76 males). Generalized estimating equations (GEE) were performed to assess between-group (CWS versus CWNS) differences on the GFTA-2. Additionally, within-group correlations were performed to explore the relation between CWS' speech sound articulation abilities and their stuttering frequency and severity, as well as their sound prolongation index (SPI; Schwartz & Conture, 1988)., Results: No significant differences were found between the articulation scores of preschool-age CWS and CWNS. However, there was a small gender effect for the 5-year-old age group, with girls generally exhibiting better articulation scores than boys. Additional findings indicated no relation between CWS' speech sound articulation abilities and their stuttering frequency, severity, or SPI., Conclusions: Findings suggest no apparent association between speech sound articulation-as measured by one standardized assessment (GFTA-2)-and childhood stuttering for this sample of preschool-age children (N=277)., Educational Objectives: After reading this article, the reader will be able to: (1) discuss salient issues in the articulation literature relative to children who stutter; (2) compare/contrast the present study's methodologies and main findings to those of previous studies that investigated the association between childhood stuttering and speech sound articulation; (3) identify future research needs relative to the association between childhood stuttering and speech sound development; (4) replicate the present study's methodology to expand this body of knowledge., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A reduction in urinary nitrogen (N) excretion from dairy cows fed pasture containing a high N concentration in the dry matter (DM) will have environmental benefits, because losses to soil water and air by leachate and nitrous oxides (N2O) will be reduced. Condensed tannins (CT) reduce digestion of N, and provision as a dietary additive could have nutritional benefits for production, but the amount required and the responses to different sources of CT on milk production have not been defined. Two experiments were conducted to evaluate effects of supplementation with CT extracted from black wattle (Acacia mearnsii De Wild.) on milk production and faecal N concentration by lactating dairy cows grazing a vegetative Perennial ryegrass (Lolium perenne L.)-based pasture. In one experiment, CT was administered as a drench, twice daily, to 38 multiparous Holstein-Friesian cows assigned to four treatments; control (CONT, 0 g/day), low CT (LCT, 111 g/day), medium CT (MCT, 222 g/day) and high CT (HCT, 444 g/day), grazing as a single group. The CT supplementation affected milk yield (P < 0.001) with a trend of declining milk yield as CT concentration increased from about 0.6 to about 2.9% of dietary DM. Milk urea nitrogen (MUN) decreased at MCT and HCT levels of supplementation (P < 0.01) but milk fat, CP and lactose percentage were not affected by CT supplementation. The CT supplementation increased N concentration in faeces for LCT and MCT treatments (P < 0.05), suggesting partitioning of dietary N away from urine. When CT was pelleted with grain, in a second experiment and fed twice daily as a supplement at milking, it reduced the acceptability relative to pellets without CT, and tended to lower milk production from 25.4 to 24.5 kg/day, although the decline was not significant (P > 0.05). The diet of cows fed pellets with CT contained about 1.2% CT in the DM but neither milk constituents nor MUN were affected by CT-supplemented grain (P > 0.05). These findings demonstrate beneficial effects for production of low concentrations (c. 0.6% DM) of CT from black wattle when given to cows grazing pasture with an N concentration of 3.8%, and suggest a diversion of N from urine, but when CT exceeded about 1.4% of dietary DM, milk production was depressed. The value of supplementing a pasture diet for lactating dairy cows with black wattle tannin extract will depend on costs of supplementation, returns from milk production and liabilities associated with N losses to urine.

Shale gas production represents a large potential source of natural gas for the nation. The scale and rapid growth in shale gas development underscore the need to better understand its environmental implications, including water consumption. This study estimates the water consumed over the life cycle of conventional and shale gas production, accounting for the different stages of production and for flowback water reuse (in the case of shale gas). This study finds that shale gas consumes more water over its life cycle (13-37 L/GJ) than conventional natural gas consumes (9.3-9.6 L/GJ). However, when used as a transportation fuel, shale gas consumes significantly less water than other transportation fuels. When used for electricity generation, the combustion of shale gas adds incrementally to the overall water consumption compared to conventional natural gas. The impact of fuel production, however, is small relative to that of power plant operations. The type of power plant where the natural gas is utilized is far more important than the source of the natural gas.

Background: Single-incision laparoscopic (SIL) colectomy has gained significant momentum with anticipated benefit of improved cosmesis. Feasibility and safety of SIL colectomy have been shown; however, benefits are not well defined. The purpose of this study is to directly compare outcomes of SIL sigmoid colectomy for diverticular disease with standard multiport laparoscopic (LAP) technique., Methods: SIL sigmoid colectomy cases performed for diverticular disease between August 2009 and July 2011 were case matched for age, gender, body mass index, American Society of Anesthesiologists score, previous abdominal operation, and need to mobilize the splenic flexure and compared with an equal number of LAP cases. Data analyzed included operative time, estimated blood loss, procedure conversion, incision length, length of hospital stay (LOS), 30-d hospital readmission, and postoperative pain scores., Results: Twenty patients were analyzed in each group with no significant differences found in the six case-matching criteria. Operative time, conversions, estimated blood loss, surgical site infection, and hospital readmissions were similar. The mean incision length for both groups was 5cm (P=0.72). LOS was 3.7d for the SIL group, which was >1d shorter than that for the LAP group (5.0d; P<0.05). Pain score at post-anesthesia care unit discharge and total amount of narcotic pain medication delivered in the post-anesthesia care unit was significantly less in the SIL group (P<0.05), as was maximum visual analog scale pain score on postoperative day 1 and postoperative day 2 (P≤0.01)., Conclusions: SIL sigmoid colectomy is associated with noncosmetic benefits, including a reduction in early postoperative pain and decreased LOS. These findings may be related to reduced abdominal wall trauma., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: The aim of this single-site, randomized, controlled, double-blind, 3-arm parallel study was to determine the effectiveness of a prophylaxis paste containing 15% calcium sodium phosphosilicate (CSPS; NovaMin(®) ) with and without fluoride in reducing dentine hypersensitivity immediately after a single application and 28 days following dental scaling and root planing., Materials & Methods: Overall, 151 subjects were enrolled in this study. All subjects received a scaling and root planing procedure followed by a final prophylaxis step using one of three different prophylaxis pastes: Test-A (15% NovaMin(®) and NaF), Test-B (15% NovaMin(®) ) and a control. Dentine hypersensitivity was assessed by tactile stimulus (Yeaple Probe(®) ) and by air blast (Schiff scale) at baseline, immediately after and 28 days after a prophylaxis procedure. One hundred and forty-nine subjects completed the study., Results: Subjects having received the test prophylaxis pastes showed statistically lower (anova, p < 0.05) dentine hypersensitivity compared with the control group immediately after the prophylaxis procedure (Yeaple Probe(®) : Test-A = 20.9 ± 12.6, Test-B = 22.7 ± 12.9, Control=11.2 ± 3.1; Schiff score: Test-A = 1.1 ± 0.6, Test-B = 1.1 ± 0.6, Control = 2.0 ± 0.7) and after 28 days (Yeaple probe: Test-A = 21.5 ± 11.9, Test-B = 20.6 ± 11.3, Control = 11.8 ± 6.0; Schiff score: Test-A = 1.0 ± 0.6, Test-B = 1.0 ± 0.6, Control = 2.0 ± 0.7)., Conclusions: In conclusion, the single application of both fluoridated and non-fluoridated prophylaxis pastes containing 15% CSPS (NovaMin(®) ) provided a significant reduction of dentine hypersensitivity up to at least 28 days., (© 2013 John Wiley & Sons A/S.)

Background: Full thickness rectal prolapse (FTRP) is managed with an abdominal or perineal operation. Traditionally, the approach has been determined by patient age and comorbidities. Our aim was to determine operative trends and outcomes for repair of FTRP in elderly patients using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database., Study Design: We queried the ACS NSQIP database from 2006 to 2009 for patients with FTRP who were 70 years of age or older. Patients were grouped according to type of surgical repair: laparoscopic (LR), open (OR), or perineal (PR) technique. We reviewed demographics, operative trends of surgical technique, and short-term outcomes for each group., Results: A total of 816 patients were analyzed; 596 (73%) PR, 130 (16%) OR, and 90 (11%) LR patients. Patients who received OR and LR had lower mean American Society of Anesthesiologists (ASA) scores than PR patients (2.6, 2.5, and 2.7, respectively, p < 0.001). The percentage of LR and OR procedures decreased as age increased by decade; the inverse was seen for PR (p < 0.001). The distribution of operative techniques has not changed from year to year. Length of stay was significantly shorter for LR (3.77 days) and PR (3.44 days) patients vs OR patients (6.23 days) (p = 0.01). Complication rates were 2.22%, 8.72%, and 12.31% for LR, PR, and OR, respectively (p = 0.021). Open surgery was the only factor associated with an increased complication rate, with an odds ratio of 6.29 (95% CI 1.38 to 28.6, p < 0.02)., Conclusions: Despite the appeal of perineal proctectomy in the elderly and debilitated patient, the approach to FTRP is slowly evolving in the era of laparoscopic surgery. Laparoscopic repair of FTRP in the elderly is associated with improved short-term outcomes when compared with OR and PR., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The primary objective of this study was to compare the effectiveness of NUPRO Sensodyne Prophylaxis Paste with NovaMin, with and without fluoride, to a standard prophylaxis paste without fluoride (control) in reducing dentin hypersensitivity immediately after a single application following dental scaling and root planing. The secondary objective was to compare the duration of sensitivity relief up to 28 days after a single application of the NUPRO pastes with NovaMin compared to the control paste., Methods: This was a randomized, single-center, controlled, three-treatment, parallel-group study conducted at Salus Research in Fort Wayne, Indiana. Male and female subjects who met all inclusion/exclusion criteria and had two non-adjacent sensitive teeth based on tactile (Yeaple probe) and air blast assessments, were enrolled in the study. At baseline, tactile and air blast stimuli were administered and subjects were stratified according to their baseline air blast (Schiff) scores into one of three treatment groups: Group A (NovaMin without fluoride), Group B (NovaMin with fluoride) or Group C (NUPRO classic prophylaxis paste without fluoride). Subjects were then assessed post-treatment and at a 28-day follow-up using tactile and air blast methods., Results: A total of 139 patients completed the study. Subjects having received the NovaMin containing prophylaxis pastes (Groups A and B) showed statistically lower (ANOVA, P< 0.05) dentin hypersensitivity compared to the control group immediately after the prophylaxis procedure. Group A tactile improvements were 86% immediate, and 88% after 28 days; air blast improvements were 49% immediate, and 50% after 28 days. Group B tactile improvements were 67% immediate, and 65% after 28 days; air blast improvements were 43% immediate, and 34% after 28 days. Group C experienced little improvement in tactile and air blast scores, 9% and 4% respectively, immediately following treatment, and 10% and 1% respectively after 28 days. At both time points, the reduction in sensitivity was meaningful and significantly better than in the group receiving a standard prophylaxis paste as the comparator (P< 0.05). Both NovaMin pastes were effective and there was no statistical difference between the pastes with and without fluoride. There were no adverse events reported during the course of this study.

Cancer-associated inflammation is thought to be a barrier to immune surveillance, particularly in pancreatic ductal adenocarcinoma (PDA). Gr-1(+) CD11b(+) cells are a key feature of cancer inflammation in PDA, but remain poorly understood. Using a genetically engineered mouse model of PDA, we show that tumor-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) is necessary and sufficient to drive the development of Gr-1(+) CD11b(+) cells that suppressed antigen-specific T cells. In vivo, abrogation of tumor-derived GM-CSF inhibited the recruitment of Gr-1(+) CD11b(+) cells to the tumor microenvironment and blocked tumor development-a finding that was dependent on CD8(+) T cells. In humans, PDA tumor cells prominently expressed GM-CSF in vivo. Thus, tumor-derived GM-CSF is an important regulator of inflammation and immune suppression within the tumor microenvironment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The purpose of the present study was to investigate the underlying constructs of the Communication Attitude Test for Preschool and Kindergarten Children Who Stutter (KiddyCAT; Vanryckeghem & Brutten, 2007), especially those related to awareness of stuttering and negative speech-associated attitudes., Method: Participants were 114 preschool-age children who stutter (CWS; n=52; 15 females) and children who do not stutter (CWNS; n=62; 31 females). Their scores on the KiddyCAT were assessed to determine whether they differed with respect to talker group (CWS vs. CWNS), chronological age, younger versus older age groups, and gender. A categorical data principal components factor analysis (CATPCA) assessed the quantity and quality of the KiddyCAT dimensions., Results: Findings indicated that preschool-age CWS scored significantly higher than CWNS on the KiddyCAT, regardless of age or gender. Additionally, the extraction of a single factor from the CATPCA indicated that one dimension-speech difficulty-appears to underlie the KiddyCAT items., Conclusions: As reported by its test developers, the KiddyCAT differentiates between CWS and CWNS. Furthermore, one factor, which appears related to participants' attitudes towards speech difficulty, underlies the questionnaire. Findings were taken to suggest that children's responses to the KiddyCAT are related to their perception that speech is difficult, which, for CWS, may be associated with relatively frequent experiences with their speaking difficulties (i.e., stuttering)., Learning Outcomes: After reading this article, the reader will be able to: (1) Better understand the concepts of attitude and awareness; (2) compare historical views with more recent empirical findings regarding preschool-age CWS' attitudes/awareness towards their stuttering; (3) describe the underlying dimension of the KiddyCAT questionnaire; (4) interpret KiddyCAT results and describe implications of those results., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Laparoscopic colorectal surgery has advantages over open surgery including shorter postoperative length of hospital stay, early return of bowel function, decreased complications and reduced postoperative pain. Innovative minimally invasive surgery techniques such as single-incision laparoscopic surgery (SIL) have emerged to further enhance outcomes of conventional laparoscopy. This technique uses a single small incision for access of all instruments and specimen extraction. This concept has been proposed to improve cosmesis and enhance recovery. Technological advances have been introduced to overcome the challenges of co-axial instrument movement and collision that is inherent to SIL surgery. The application of SIL techniques to colorectal surgery is in its infancy, but gaining significant momentum. Early case reports and series have shown feasibility and safety. Emerging comparative studies of SIL colectomy to standard laparoscopic techniques are providing evidence of equivalency with potential benefit in outcomes such as reduced early postoperative pain and shortened length of hospital stay. The application of the SIL platform to robotics and transanal surgery demonstrates the broadening scope of this innovative field. However, we must be cognizant of the impact on surgeon training and resident education. In this review we present the current evidence supporting the application of SIL to colorectal surgery.

Objective: To determine whether a difference in systolic blood pressure readings between arms can predict a reduced event free survival after 10 years., Design: Cohort study., Setting: Rural general practice in Devon, United Kingdom., Participants: 230 people receiving treatment for hypertension in primary care., Intervention: Bilateral blood pressure measurements recorded at three successive surgery attendances., Main Outcome Measures: Cardiovascular events and deaths from all causes during a median follow-up of 9.8 years., Results: At recruitment 24% (55/230) of participants had a mean interarm difference in systolic blood pressure of 10 mm Hg or more and 9% (21/230) of 15 mm Hg or more; these differences were associated with an increased risk of all cause mortality (adjusted hazard ratio 3.6, 95% confidence interval 2.0 to 6.5 and 3.1, 1.6 to 6.0, respectively). The risk of death was also increased in 183 participants without pre-existing cardiovascular disease with an interarm difference in systolic blood pressure of 10 mm Hg or more or 15 mm Hg or more (2.6, 1.4 to 4.8 and 2.7, 1.3 to 5.4). An interarm difference in diastolic blood pressure of 10 mm Hg or more was weakly associated with an increased risk of cardiovascular events or death., Conclusions: Differences in systolic blood pressure between arms can predict an increased risk of cardiovascular events and all cause mortality over 10 years in people with hypertension. This difference could be a valuable indicator of increased cardiovascular risk. Bilateral blood pressure measurements should become a routine part of cardiovascular assessment in primary care.

Background: Differences in systolic blood pressure (SBP) of 10 mm Hg or more or 15 mm Hg or more between arms have been associated with peripheral vascular disease and attributed to subclavian stenosis. We investigated whether an association exists between this difference and central or peripheral vascular disease, and mortality., Methods: We searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Medline In Process databases for studies published before July, 2011, showing differences in SBP between arms, with data for subclavian stenosis, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or survival. We used random effects meta-analysis to combine estimates of the association between differences in SBP between arms and each outcome., Findings: We identified 28 eligible studies for review, 20 of which were included in our meta-analyses. In five invasive studies using angiography, mean difference in SBP between arms was 36·9 mm Hg (95% CI 35·4-38·4) for proven subclavian stenosis (>50% occlusion), and a difference of 10 mm Hg or more was strongly associated with subclavian stenosis (risk ratio [RR] 8·8, 95% CI 3·6-21·2). In non-invasive studies, pooled findings showed that a difference of 15 mm Hg or more was associated with peripheral vascular disease (nine cohorts; RR 2·5, 95% CI 1·6-3·8; sensitivity 15%, 9-23; specificity 96%, 94-98); pre-existing cerebrovascular disease (five cohorts; RR 1·6, 1·1-2·4; sensitivity 8%, 2-26; specificity 93%, 86-97); and increased cardiovascular mortality (four cohorts; hazard ratio [HR] 1·7, 95% CI 1·1-2·5) and all-cause mortality (HR 1·6, 1·1-2·3). A difference of 10 mm Hg or higher was associated with peripheral vascular disease (five studies; RR 2·4, 1·5-3·9; sensitivity 32%, 23-41; specificity 91%, 86-94)., Interpretation: A difference in SBP of 10 mm Hg or more, or of 15 mm Hg or more, between arms might help to identify patients who need further vascular assessment. A difference of 15 mm Hg or more could be a useful indicator of risk of vascular disease and death., Funding: Royal College of General Practitioners, South West GP Trust, and Peninsula Collaboration for Leadership in Applied Health Research and Care., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The technologies and practices that have enabled the recent boom in shale gas production have also brought attention to the environmental impacts of its use. It has been debated whether the fugitive methane emissions during natural gas production and transmission outweigh the lower carbon dioxide emissions during combustion when compared to coal and petroleum. Using the current state of knowledge of methane emissions from shale gas, conventional natural gas, coal, and petroleum, we estimated up-to-date life-cycle greenhouse gas emissions. In addition, we developed distribution functions for key parameters in each pathway to examine uncertainty and identify data gaps such as methane emissions from shale gas well completions and conventional natural gas liquid unloadings that need to be further addressed. Our base case results show that shale gas life-cycle emissions are 6% lower than conventional natural gas, 23% lower than gasoline, and 33% lower than coal. However, the range in values for shale and conventional gas overlap, so there is a statistical uncertainty whether shale gas emissions are indeed lower than conventional gas. Moreover, this life-cycle analysis, among other work in this area, provides insight on critical stages that the natural gas industry and government agencies can work together on to reduce the greenhouse gas footprint of natural gas.

In all multicellular animals, successful embryogenesis is dependent on the ability of cells to detect the status of the local environment and respond appropriately. The nature of the extracellular environment is communicated to the intracellular compartment by ligand/receptor interactions at the cell surface. The Wnt canonical and non-canonical signalling pathways are found in the most primitive metazoans, and they play an essential role in the most fundamental developmental processes in all multicellular organisms. Vertebrates have expanded the number of Wnts and Frizzled receptors and have additionally evolved novel Wnt receptor families (Ryk, Ror). The multiplicity of potential interactions between Wnts, their receptors and downstream effectors has exponentially increased the complexity of the signal transduction network. Signalling through each of the Wnt pathways, as well as crosstalk between them, plays a critical role in the establishment of the complex architecture of the vertebrate central nervous system. In this review, we explore the signalling networks triggered by non-canonical Wnt/receptor interactions, focussing on the emerging roles of the non-conventional Wnt receptors Ryk and Ror. We describe the role of these pathways in neural tube formation and axon guidance where Wnt signalling controls tissue polarity, coordinated cell migration and axon guidance via remodelling of the cytoskeleton., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To examine the implications of an ontology of aggressive behavior which divides aggression into reactive, affective, defensive, impulsive (RADI) or "emotionally hot"; and planned, instrumental, predatory (PIP) or "emotionally cold." Recent epidemiological, criminological, clinical and neuroscience studies converge to support a connection between emotional and trauma related psychopathology and disturbances in the emotions, self-regulation and aggressive behavior which has important implications for diagnosis and treatment, especially for delinquent populations., Method: Selective review of preclinical and clinical studies in normal, clinical and delinquent populations., Results: In delinquent populations we observe an increase in psychopathology, and especially trauma related psychopathology which impacts emotions and self-regulation in a manner that hotly emotionally charged acts of aggression become more likely. The identification of these disturbances can be supported by findings in cognitive neuroscience. These hot aggressive acts can be delineated from planned or emotionally cold aggression., Conclusion: Our findings support a typology of diagnostic labels for disruptive behaviors, such as conduct disorder and oppositional defiant disorder, as it appears that these acts of hot emotional aggression are a legitimate target for psychopharmacological and other trauma specific interventions. The identification of this subtype of disruptive behavior disorders leads to more specific clinical interventions which in turn promise to improve hitherto unimpressive treatment outcomes of delinquents and patients with disruptive behavior.

T cells often make sequential contacts with multiple DCs in the lymph nodes and are likely to be equipped with mechanisms that allow them to sum up the successive signals received. We found that a period of stimulation as short as two hours could imprint on a T cell a "biochemical memory" of that activation signal that persisted for several hours. This was evidenced by more rapid induction of activation markers and earlier commitment to proliferation upon subsequent stimulation, even when that secondary stimulation occurred hours later. Upregulation of the immediate early gene product c-fos, a component of the AP-1 transcription factor, was maximal by 1-2 hours of stimulation, and protein levels remained elevated for several hours after stimulus withdrawal. Moreover, phosphorylated forms of c-fos that are stable and transcriptionally active persisted for a least a day. Upon brief antigenic stimulation in vivo, we also observed a rapid upregulation of c-fos that could be boosted by subsequent stimulation. Accumulation of phosphorylated c-fos may therefore serve as a biochemical fingerprint of previous suboptimal stimulation, leaving the T cell poised to rapidly resume its activation program upon its next encounter with an antigen-bearing DC.

Background: Previous reviews demonstrate uncertainty about the effectiveness of nurse-led interventions in the management of hypertension. No specific reviews in diabetes have been identified. We have systematically reviewed the evidence for effectiveness of nurse-led interventions for people with diabetes mellitus., Methods: In this systematic review and meta-analysis, searches of Medline, Embase, CINAHL and the Cochrane Central Trials register were undertaken to identify studies comparing any intervention conducted by nurses in managing hypertension in diabetes with usual doctor-led care. Additional citations were identified from papers retrieved and correspondence with authors. Outcome measures were absolute systolic and diastolic blood pressure, change in blood pressure, proportions achieving study target blood pressure and proportions prescribed anti-hypertensive medication., Results:   Eleven studies were identified. Interventions included adoption of treatment algorithms, nurse-led clinics and nurse prescribing. Meta-analysis showed greater reductions in blood pressure in favour of any nurse-led interventions (systolic weighted mean difference -5.8 mmHg, 95% CI -9.6 to -2.0; diastolic weighted mean difference -4.2 mmHg, 95% CI -7.6 to -0.7) compared with usual doctor-led care. No overall superiority in achievement of study targets or in the use of medication was evident for any nurse-based interventions over doctor-led care., Conclusions: There is some evidence for improved blood pressure outcomes with nurse-led interventions for hypertension in people with diabetes compared with doctor-led care. Nurse-based interventions require an algorithm to structure care and there is some preliminary evidence for better outcomes with nurse prescribing. Further work is needed to elucidate which nurse-led interventions are most effective., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Colonic vascular ectasia is a condition characterized by dilated submucosal veins, venules, or capillaries found commonly in patients with lower gastrointestinal hemorrhage. We present a case of colorectal ectasia associated with ischemia and an inferior mesenteric artery aneurysm. These pathologic findings may be the result of the vascular ectasia and may add to the natural history of this condition., (Copyright © 2011 Annals of Vascular Surgery Inc. All rights reserved.)

Aims: To assess the efficacy of herb and plant extracts in the management of asthma., Method: Systematic review and meta-analysis. Multiple database searches identified randomised placebo controlled trials of herbal interventions reporting at least one primary outcome measure. Where possible data were combined for meta-analysis. Primary outcome measures were lung function, exacerbations and reduction in corticosteroid use. Secondary outcome measures were symptoms and symptom scores, use of reliever medications, changes in rates of consultation and adverse effects., Results: Twenty-six studies reporting on 20 herbal preparations were included. Two of six studies reporting change in FEV1 were positive. Little data was available on frequency of exacerbations. For primary outcomes single studies of Boswellia, Mai-Men-Dong-Tang, Pycnogenol, Jia-Wei-Si-Jun-Zi-Tang and Tylophora indica showed potential to improve lung function, and a study of 1.8-Cineol (eucalyptol) showed reduced daily oral steroid dosage., Conclusions: Improvements in symptoms were not strongly supported by objective changes. Most trials were of small sample size, short duration, and poor methodology. Further adequately powered trials are needed to assess these compounds. Such trials should conform to CONSORT guidance, report standardised spirometry, and use validated symptom and severity scores. No recommendations for herbal treatment of asthma can be made from the current evidence.

Objective: To review trials of nurse led interventions for hypertension in primary care to clarify the evidence base, establish whether nurse prescribing is an important intervention, and identify areas requiring further study., Design: Systematic review and meta-analysis., Data Sources: Ovid Medline, Cochrane Central Register of Controlled Trials, British Nursing Index, Cinahl, Embase, Database of Abstracts of Reviews of Effects, and the NHS Economic Evaluation Database., Study Selection: Randomised controlled trials of nursing interventions for hypertension compared with usual care in adults., Data Extraction: Systolic and diastolic blood pressure, percentages reaching target blood pressure, and percentages taking antihypertensive drugs. Intervention effects were calculated as relative risks or weighted mean differences, as appropriate, and sensitivity analysis by study quality was undertaken., Data Synthesis: Compared with usual care, interventions that included a stepped treatment algorithm showed greater reductions in systolic blood pressure (weighted mean difference -8.2 mm Hg, 95% confidence interval -11.5 to -4.9), nurse prescribing showed greater reductions in blood pressure (systolic -8.9 mm Hg, -12.5 to -5.3 and diastolic -4.0 mm Hg, -5.3 to -2.7), telephone monitoring showed higher achievement of blood pressure targets (relative risk 1.24, 95% confidence interval 1.08 to 1.43), and community monitoring showed greater reductions in blood pressure (weighted mean difference, systolic -4.8 mm Hg, 95% confidence interval -7.0 to -2.7 and diastolic -3.5 mm Hg, -4.5 to -2.5)., Conclusions: Nurse led interventions for hypertension require an algorithm to structure care. Evidence was found of improved outcomes with nurse prescribers from non-UK healthcare settings. Good quality evidence from UK primary health care is insufficient to support widespread employment of nurses in the management of hypertension within such healthcare systems.

Capturing urine and spreading it evenly across a paddock reduces the risk of nitrogen loss to the environment. This study investigated the effect of 16h/d removal from pasture on the capture of urination events, milk production, pasture intake, and animal welfare from cows grazing fresh pasture in early and late lactation. Forty-eight Holstein-Friesian cows in early [470+/-47kg of body weight (BW); 35+/-9 days in milk] and late (498+/-43kg of BW; 225+/-23 days in milk) lactation were allocated to 3 treatment groups. Cows had access to pasture for either 4h after each milking (2 x 4), for 8h between morning and afternoon milkings (1 x 8), or for 24h, excluding milking times (control). When not grazing, the 2 x 4 and 1 x 8 groups were confined to a plastic-lined loafing area with a woodchip surface. In early lactation, the proportion of urinations on pasture and laneways was reduced from 89% (control) to 51% (1 x 8) and 54% (2 x 4) of total urinations. The 1 x 8 cows ate less pasture [10.9kg of dry matter (DM)/cow per day] than the control (13.6kg of DM/cow per day) and 2 x 4 (13.0kg of DM/cow per day) cows, which did not differ from each other. The 1 x 8 and 2 x 4 cows produced less milk (21 and 22kg of milk/cow per day, respectively) compared with control cows (24kg of milk/cow per day). There were no differences in BW or body condition score (BCS) change across treatment groups, with all groups gaining BW and BCS during the experimental period. In late lactation, there was no difference in pasture intake (mean=8.8kg of DM/cow per day), milk production (mean=10kg of milk/cow per day), and BW or BCS change (mean=3.7kg and -0.2U/cow per week, respectively) between treatment groups. As in early lactation, urinations on pasture and laneways were reduced from 85% (control) to 56% (1 x 8) and 50% (2 x 4) of total urinations. These findings highlight an opportunity to maintain performance and welfare of grazing cows in early and late lactation while capturing additional urine. This can subsequently be spread evenly across pasture to minimize nitrogen loss to the environment., (Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Trp53 loss of function has previously been shown to rescue tissue maintenance and developmental defects resulting from DNA damage or DNA-repair gene mutations. Here, we report that p53 deficiency severely exacerbates tissue degeneration caused by mosaic deletion of the essential genome maintenance regulator Atr. Combined loss of Atr and p53 (Trp53(-/-)Atr(mKO)) led to severe defects in hair follicle regeneration, localized inflammation (Mac1(+)Gr1(+) infiltrates), accelerated deterioration of the intestinal epithelium and synthetic lethality in adult mice. Tissue degeneration in Trp53(-/-)Atr(mKO) mice was characterized by the accumulation of cells maintaining high levels of DNA damage. Moreover, the elevated frequency of these damaged cells in both progenitor and downstream compartments in Trp53(-/-)Atr(mKO) skin coincided with delayed compensatory tissue renewal from residual ATR-expressing cells. Together, our results indicate that the combined loss of Atr and Trp53 in adult mice leads to the accumulation of highly damaged cells, which, consequently, impose a barrier to regeneration from undamaged progenitors.

This study investigated the effect of restricting grazing time on circulating concentrations of ghrelin, nonesterified fatty acids (NEFA), and glucose before, and foraging behavior of dairy cows during, the first grazing session of the day (GS, 0800-1200 h). Forty-eight Holstein-Friesian cows (470 +/- 47 kg of BW; 35 +/- 9 d in milk) were strip-grazed on a perennial ryegrass pasture for either 4 h after each milking (2 x 4), 8 h between milkings (1 x 8), or the 24-h period excluding milking times (CTL). Cows were bled before the GS; plasma was analyzed for ghrelin and serum for glucose and NEFA. Herbage mass was measured pregrazing (0730 h), during and at the end of the GS (1200 h), and postgrazing (24 h after the first measurement). Herbage mass data were fitted to a model to estimate herbage disappearance rates. Herbage intake and bite mass were calculated using herbage mass disappearance and behavioral measurements. Bite rate, eating, searching, ruminating, and idling time were determined during the GS for each cow. No difference in glucose concentration was found between treatments. Concentrations of NEFA and ghrelin were the greatest for cows in the 1 x 8 treatment. Daily herbage intake did not differ between treatments; however, during the GS 1 x 8 had a greater herbage intake than 2 x 4 and CTL. Bite mass differed between treatments and throughout the GS. Bite mass was smallest for CTL during the first 60 min and greatest during the last 90 min, when cows in the 2 x 4 treatment had the smallest bite mass. Cows in 1 x 8 spent the longest time eating and the least time searching and ruminating. Eating time was greatest for 1 x 8 during the first 60 and last 90 min of the GS. Searching time only differed in the second 60 min, when it was the lowest for 1 x 8. Cows from all treatments did not ruminate during the first 120 min. Cows in CTL had the greatest rumination time during the last 90 min. The model fitted to represent dynamics of herbage mass disappearance presented differences in the fractional herbage disappearance rate. There was an interaction between treatment and time in herbage depletion rate. The results of this study present a fuller picture of foraging dynamics during the first 4 h of grazing and its potential relationship with physiological markers of hunger as affected by grazing management.

The resurgent theory of cancer immunosurveillance holds that the immune system plays an important role in the suppression of tumors, particularly in the elimination of early neoplastic lesions. Tumors with reduced immunogenicity or those that have acquired mechanisms to suppress immune effector functions, however, can emerge from this selection pressure and grow progressively. This is an especially important issue in pancreatic cancer, which although inflammatory in vivo is nevertheless highly aggressive and nearly always lethal. Here, we review emerging data obtained from novel genetically defined mouse models of pancreatic adenocarcinoma that suggest that the immune system may be complicit in the inception and progression of pancreatic cancer. Host immune cells with suppressive properties infiltrate the pancreas early during tumorigenesis, even at the earliest stages of neoplasia, preceding and effectively undermining any lymphocytes with potential antitumor function. Thus, in pancreatic adenocarcinoma, the failure of immunosurveillance is likely an early event during tumorigenesis, a concept that carries important implications for the design of novel immunotherapeutics in this disease.

Background: Previous studies have identified a substantial prevalence of a blood pressure difference between arms in various populations, but not patients with type 2 diabetes. Recognition of such a difference would be important as a potential cause of underestimation of blood pressure., Aim: To measure prevalence of an inter-arm blood pressure difference in patients with type 2 diabetes, and to estimate how frequently blood pressure measurements could be erroneously underestimated if an inter-arm difference is unrecognised., Design of Study: Cross-sectional study., Setting: Five surgeries covered by three general practices, Devon, England., Method: Patients with type 2 diabetes underwent bilateral simultaneous blood pressure measurements using a validated protocol. Mean blood pressures were calculated for each arm to derive mean systolic and diastolic differences, and to estimate point prevalence of predefined magnitudes of difference., Results: A total of 101 participants were recruited. Mean age was 66 years (standard deviation [SD] = 13.9 years); 59% were male, and mean blood pressure was 138/79 mmHg (SD = 15/10 mmHg). Ten participants (10%; 95% confidence interval [CI] = 4 to 16) had a systolic inter-arm difference > or =10 mmHg; 29 (29%; 95% CI = 20 to 38) had a diastolic difference >/=5 mmHg; and three (3%; 95% CI = 0 to 6) a diastolic difference > or =10 mmHg. No confounding variable was observed to account for the magnitude of an inter-arm difference., Conclusion: A systolic inter-arm difference > or =10 mmHg was observed in 10% of patients with diabetes. Failure to recognise this would misclassify half of these as normotensive rather than hypertensive using the lower-reading arm. New patients with type 2 diabetes should be screened for an inter-arm blood pressure difference.

Background: Herb and plant based preparations are a popular treatment for asthma, although there remain concerns as to their efficacy and safety. In Western societies, motivations for using such treatments may be both positive and negative, with their perceived safety and dissatisfaction with conventional medicine among them. In China such treatments are more commonly used and many compounds considered 'conventional' are derived from herbs or plants., Objectives: To assess the efficacy and safety of herb and plant extracts in the management of chronic asthma., Search Strategy: The Cochrane Airways Group Trials Register, CENTRAL, MEDLINE, EMBASE and AMED were searched with pre-defined terms. Searches are current as of February 2007., Selection Criteria: Randomised placebo controlled trials of any herb or plant extract were eligible. Study participants had to have a primary diagnosis of asthma. Studies in both adults and children were eligible for the review., Data Collection and Analysis: Two reviewers assessed studies for suitability. Data were extracted and double-checked., Main Results: Twenty-seven studies (29 experimental groups) met the review entry criteria, randomising a total of 1925 participants. The studies identified assessed the effects of 21 different herbal preparations. Study quality varied considerably, and the sample sizes were often small. For primary outcomes (exacerbations, steroids use and lung function measurements): Two out of six studies reporting change in FEV1 were positive, with very few data available on the frequency of exacerbations. One study which did report these data was negative. Health-related quality of life was only measured in one trial., Authors' Conclusions: The evidence base for the effects of herbal treatments is hampered by the variety of treatments assessed, poor reporting quality of the studies and lack of available data. The data that are available from the studies provide only a small insight into the long-term efficacy and harm profiles of these treatments. The absence of common endpoint measurements limits the validity of our findings further. Positive findings in this review warrant additional well-designed trials in this area.

Rynaxypyr is a highly potent and selective activator of insect ryanodine receptors with exceptional activity on a broad range of Lepidoptera. A strong correlation between insecticidal activity and ryanodine receptor activation is observed along with selective activity against insect over mammalian receptors. The synthesis and biological results are presented.

The human telomerase reverse transcriptase (hTERT) is nearly universally overexpressed in human cancer, contributes critically to oncogenesis, and is recognized by cytotoxic T cells that lyse tumors. CD8+ T cells specific for hTERT naturally occur in certain populations of cancer patients in remission, but it remains poorly understood whether such T cells could contribute to tumor immunosurveillance. To address this issue, we induced hTERT-specific T cells in vivo via peptide vaccination in 19 patients with metastatic breast cancer who otherwise had no measurable T-cell responses to hTERT at baseline. Tumor-infiltrating lymphocytes (TIL) were evident after, but not before vaccination, with 4% to 13% of postvaccine CD8+ TIL specific for the immunizing hTERT peptide. Induction of TIL manifested clinically with tumor site pain and pruritus and pathologically with alterations in the tumor microenvironment, featuring histiocytic accumulation and widespread tumor necrosis. hTERT-specific CD8+ T cells were also evident after vaccination in the peripheral blood of patients and exhibited effector functions in vitro including proliferation, IFN-gamma production, and tumor lysis. An exploratory landmark analysis revealed that median overall survival was significantly longer in those patients who achieved an immune response to hTERT peptide compared with patients who did not. Immune response to a control cytomegalovirus peptide in the vaccine did not correlate with survival. These results suggest that hTERT-specific T cells could contribute to the immunosurveillance of breast cancer and suggest novel opportunities for both therapeutic and prophylactic vaccine strategies for cancer.

The dynamics of cancer immunosurveillance remain incompletely understood, hampering efforts to develop immunotherapy of cancer. We evaluated the evolving in vivo immune response to a spontaneous tumor in a genetically defined mouse model of pancreatic ductal adenocarcinoma from the inception of preinvasive disease to invasive cancer. We observed a prominent leukocytic infiltration even around the lowest grade preinvasive lesions, but immunosuppressive cells, including tumor-associated macrophages, myeloid-derived suppressor cells (MDSC), and regulatory T cells (Treg), dominated the early response and persisted through invasive cancer. Effector T cells, however, were scarce in preinvasive lesions, found in only a subset of advanced cancers, and showed no evidence of activation. The lack of tumor-infiltrating effector T cells strongly correlated with the presence of intratumoral MDSC with a near mutual exclusion. In vitro, we found that MDSC suppressed T-cell proliferation. Overall, our results show that suppressive cells of the host immune system appear early during pancreatic tumorigenesis, preceding and outweighing antitumor cellular immunity, and likely contribute to disease progression. Thus, in contrast to the hypothesis that an early "elimination phase" of cancer immunosurveillance is eventually overwhelmed by a growing invasive tumor, our findings suggest that productive tumor immunity may be undermined from the start. Efforts to test potent inhibitors of MDSC, tumor-associated macrophages, and Treg, particularly early in the disease represent important next steps for developing novel immunotherapy of cancer.

Background: A blood pressure (BP) difference between the upper limbs is often encountered in primary care. Knowledge of its prevalence and importance in the accurate measurement of BP is poor, representing a source of error. Current hypertension guidelines do not emphasize this., Objectives: To establish the prevalence of an inter-arm blood pressure difference (IAD) and explore its association with other indicators of peripheral vascular disease (PVD) in a hypertensive primary care population., Methods: This was a cross-sectional study. Primary care, one rural general practice, was the setting of the study. The methods were controlled simultaneous measurement of brachial BPs, ankle-brachial pressure index (ABPI) and tiptoe stress testing in 94 subjects., Results: In all, 18 of 94 [19%, 95% confidence interval (CI) 11-27%] subjects had mean systolic inter-arm difference (sIAD) > or =10 mmHg and seven of 94 (7%, 95% CI 2-12%) had mean diastolic inter-arm difference (dIAD) > or =10 mmHg. Nineteen of 91 (20%, 95% CI 12-28%) had a reduced ABPI <0.9. There was negative correlation between systolic (Pearson's correlation coefficient - 0.378; P = 0.01) and diastolic (Pearson's correlation coefficient - 0.225; P = 0.05) magnitudes of IAD with ABPI. On tiptoe testing, 9/90 subjects (10%, 95% CI 4-16%) had a pressure drop > or =20%., Conclusions: An IAD and asymptomatic PVD are common in a primary care hypertensive population. Magnitude of the IAD is inversely correlated with ABPI, supporting the hypotheses that IADs are causally linked to PVD, and that IAD is a useful marker for the presence of PVD. Consequently, detection of an IAD should prompt the clinician to screen subjects for other signs of vascular disease and target them for aggressive cardiovascular risk factor modification.

Objectives of this study were to measure the prevalence of a difference in blood pressure (BP) between arms and determine whether a difference is associated with increased risk of cardiovascular events or death. A prospective cohort study of 247 patients with hypertension was undertaken in one rural general practice in England. The main outcome measures were mean difference in BP between arms and new episodes of myocardial infarction, cerebrovascular event, onset of angina or peripheral vascular disease or death. A total of 57/247 (23%) patients had a mean difference in systolic BP between arms of >or=10 mm Hg and 8/247 (3%) had a mean difference of >or=20 mm Hg. A total of 15/247 (6%) patients had a mean difference in diastolic BP between arms of >or=10 mm Hg. Survival analysis after 4.7 years (range 3.3-5.9) showed a shorter mean survival time without event or death for patients with a difference in systolic BP of >or=10 mm Hg compared with a difference of <10 mm Hg (3.7 (95% confidence interval, 3.2-4.2) versus 4.8 (4.6-5.1) years; P<0.001; hazard ratio 2.5 (1.5-4.2), P=0.001). Difference in systolic BP of >or=10 mm Hg between arms is common in this primary care population and is associated with a shorter survival time to death or new cardiovascular event. Detection of a difference between arms may identify hypertensive patients at increased risk of cardiovascular events. Such an approach would allow more effective targeting of resources in primary prevention strategies.

A blood pressure (BP) difference between arms was first reported over 100 years ago. Knowledge of its prevalence and relevance to the accurate measurement of BP remains poor. Current hypertension guidelines do not emphasise it. The objectives of this study were to establish the best estimate of prevalence of the inter-arm difference (IAD) in the population, to consider its implications for accurate BP measurement and treatment, and to discuss its aetiology and potential as a risk marker for cardiovascular disease. Systematic literature review was carried out. The data sources were Medline EMBASE and CINAHL databases, and Index of Theses. Studies reporting prevalence rates of IAD were retrieved and considered for inclusion against explicit methodological criteria. Point prevalence rates were extracted and weighted mean prevalence rates calculated. The main outcome measures were weighted mean prevalences of systolic IAD > or =10 and > or =20 mm Hg and of diastolic IAD > or =10 mm Hg. Thirty-one studies were identified. Most had methodological weaknesses; only four met the inclusion criteria. Pooled prevalences of the IAD from these four studies were 19.6% systolic > or =10 mm Hg (95% CI 18.0-21.3%), 4.2% systolic > or =20 mm Hg (95% CI 3.4-5.1%) and 8.1% diastolic > or =10 mm Hg (95%CI 6.9-9.2%). In conclusion, an IAD is present in a substantial number of patients and should be looked for whenever diagnosis and treatment depend on accurate measurements of BP. The importance of an IAD should be better emphasised in current hypertension management guidelines. There is evidence associating an IAD with peripheral vascular disease, raising the possibility that its presence may predict cardiovascular events.

A novel class of anthranilic diamides has been discovered with exceptional insecticidal activity on a range of Lepidoptera. These compounds have been found to exhibit their action by release of intracellular Ca2+ stores mediated by the ryanodine receptor. The discovery, synthesis, structure-activity, and biological results are presented.

Aims: The salmeterol/fluticasone combination inhaler (Seretide) has been shown to be effective in the management of asthma by randomised controlled trials. This study examined whether it was also effective in clinical use in primary care., Methods: Patients attending the surgery asthma clinic with persistent symptoms despite regular inhaled corticosteroid therapy were offered Seretide. Outcome measures were symptom scores, peak flow measurements, prescriptions for relief bronchodilators, mean daily inhaled steroid dosage, and asthma treatment costs. Patients were assessed at baseline, 9 and 19 months, comparing Seretide users with other asthma clinic attenders., Results: Fifty patients were studied, 20 started Seretide. Symptom scores at entry were higher for Seretide patients than the comparison group (total score 4.2 vs 1.5; p<0.001), and reduced with Seretide, to levels below those seen in the comparison group. Study patients use of relief devices was similar at outset but significantly lower at 9 month follow up (mean 0.7 vs 2.1; 95%CI difference 0.4 to 2.4; p<0.01). Daily dosages of inhaled steroid were significantly higher at entry for the Seretide group (mean 908mcgs vs 648; p=0.041) and were reduced with Seretide to 476mcgs at 9 months (p=0.002) and 467mcgs (p=0.008) at 19 months. Mean 6 month treatment costs for study patients were higher at entry (£146.85 vs £82.74; p=0.12), rose with the addition of Seretide at 9 months (£165.27 vs £80.92; p=0.001) but were significantly reduced at 19 months(£97.35 vs £72.96; p=0.35, Seretide patients' mean cost reduction £67.92; 95%CI £21.24 to £114.60; p<0.01)., Conclusions: Seretide is effective in treating symptomatic asthma in primary care, reducing symptom scores, reliever use, and mean daily steroid requirements. When symptoms are taken into account, it also appears to be cost-effective, and treatment costs are reduced after extended follow up without loss of benefit., (Copyright © 2003 General Practice Airways Group.)

Background: Patients sometimes have differences of > or =20/10 mmHg in their blood pressure depending on which arm is measured. The prevalence and prognostic value of this finding in general practice are unknown. If these differences are due to peripheral vascular disease, these patients may be at increased risk of cardiovascular or cerebrovascular events., Objective: Our aim was to establish the frequency and prognostic value of a blood pressure difference between arms in one rural general practice., Methods: Paired blood pressure readings were collected from patients attending the surgery. The outcome measures of myocardial infarction, new diagnosis of angina, a cerebrovascular event or death were recorded prospectively., Results: A total of 280 patients were examined, and of these 13.6% had a systolic blood pressure difference (SBPD) of > or =20 mmHg, and 23.2% a diastolic blood pressure difference (DBPD) of > or =10 mmHg. Eighty-three patients were followed-up for 5.6 years. Patients with a DBPD of > or =10 mmHg showed a mean event-free survival of 3.3 years [95% confidence interval (CI) 2.2-4.4] compared with 5.0 years (95% CI 4.7-5.3) for those with a DBPD of <10 mmHg (P < 0.0001). Patients with an SBPD of > or =20 mmHg showed a mean event-free survival of 3.5 years (95% CI 2.3-4.7) compared with 4.9 years (95% CI 4.5-5.2) for an SBPD of <20 mmHg (P = 0.043)., Conclusions: During a single assessment of blood pressure, there will be a minority of patients with a difference of > or =20/10 mmHg between their right and left arms. Measurement of both arms is therefore necessary to diagnose and treat hypertension accurately. This study suggests an association between blood pressure difference and increased morbidity and mortality. Priority should be given to managing other risk factors aggressively in those patients with a reproducible blood pressure difference of > or =20/10 mmHg.