bluuebunny/crossref_metadata_2025 huggingface dataset:
A3 Identifying barriers and facilitators to improving prehospital care of asthma: views of ambulance clinicians
Authors: Shaw D , Knowles S , Siriwardena A N
Published: October 2011

Background

In 2008/2009 there were nearly 80 000 emergency hospital admissions for asthma. Current UK guidelines emphasise the importance of evidence-based prehospital assessment and treatment of asthma for improving patient outcomes and reducing hospitalisation, morbidity and mortality. National benchmarking of ambulance clinical performance indicators for asthma have revealed important unexplained variations in care across ambulance services. Little research has been undertaken to understand the reasons for poor levels of care.

Objective

The aim of this study was to gather data on ambulance clinicians' perceptions and beliefs around prevailing and best practice for management of asthma. This was used to identify the factors which prevent or enable better asthma care in ambulance services.

Methods

We used a phenomenological qualitative approach, which addresses how individuals use their experiences to make sense of their world, focusing on participants' lived experiences of care delivery for asthma. We used focus groups of ambulance clinicians to gather data on barriers and facilitators to better asthma care. Recordings and notes were taken, transcribed and then analysed using QSR NVivo 8. A coding framework was developed based on a priori concepts but with emergent themes added during the analysis.

Results

Two focus groups were conducted with eight and five participants respectively. A number of preliminary themes and subthemes were identified. The study identified issues relating to clarity of ambulance guidelines, conflicts between training and guidance, misconceptions about the importance of objective assessment and over reliance on non-objective assessment. Some practitioners believed that hospital staff were not interested in prehospital peak flow assessments.

Conclusion

Our findings will inform improved systems of care for asthma and the effect on indicators will be measured using time series methods. This approach could be used more widely to improve management of specific clinical conditions where quality of care is demonstrated to be suboptimal.
A5 Characteristics of ambulance category B calls
Authors: Turner J , Bjarkoy M
Published: October 2011

Background

One of the key recommendations of the 2005 policy document “Taking Healthcare to the patient” was that the category B 19-min response standard be replaced with more clinically focused performance measures. Before developing these new measures a clear description of the nature and type of calls within category B was needed in order to understand the case-mix of this group. We have conducted a descriptive observational study of category B ambulance calls.

Methods

The study was conducted in two parts. First, a national survey of all ambulance services in England was conducted requesting information on total number of category B calls for 1 year (2007/2008) and the numbers allocated to each AMPDS dispatch category. Secondly, we obtained 2 months of category B call dispatch records and scanned anonymised clinical patient record data from one ambulance service. This information was used to describe clinical acuity and frequency of clinical assessment and interventions.

Results

National survey—7/11 ambulance services returned data. We found that 50% of the total category B call volume is accounted for by 5 of the 32 main dispatch categories. Diabetic problems and falls were the main categories.

Analyses of clinical data—After removing duplicate records 26 882 cases were used. A quarter (25%) of cases had no assessment or intervention other than basic vital sign measurement, 50% had additional clinical assessment but no intervention and 25% required an intervention. The most frequent intervention was oxygen administration. Only 10% of cases required drugs, airway management or other procedures.

Conclusions

Category B calls comprise a population of patients without time dependant conditions and response time is therefore a poor indicator of the quality of care for this patient group.
A6 Left bundle branch block: simplified Sgarbossa criteria applied to prehospital ECGs
Authors: Viner A , Mclean S , Fitzpatrick D , Flapan A
Published: October 2011

Introduction

In patients presenting with chest pain, the presence of Left Bundle Branch Block (LBBB) on the ECG may obscure the diagnosis of acute myocardial infarction (AMI). Patients with LBBB caused by AMI are shown to benefit significantly from rapid provision of reperfusion therapy, yet evidence suggests this is often underprovided. Difficulties in the identification of AMI in these patients is the most commonly cited reason.

Aims

To determine whether the application of the simplified Sgarbossa criteria to undifferentiated chest pain patients presenting with ECG changes of LBBB, transmitted during the prehospital phase of care, will be positively predictive of a discharge diagnosis of AMI.

Methods

785 ECGs were reviewed retrospectively and categorised based on their features. Those displaying LBBB and complete patient data were evaluated using the simplified Sgarbossa criteria and a decision made as to whether the patient had suffered AMI, a process which was blind peer reviewed. Results of cardiac biomarkers were traced and the diagnosis of AMI confirmed or refuted.

Results

Of the 785 ECGs reviewed and categorised 56 (7.1%) displayed the features of LBBB and 18 were eligible for inclusion in the study. The sensitivity and specificity of the Sgarbossa criteria were 50% and 75% respectively. Inter-observer reliability was κ=0.93 (almost perfect).

Conclusion

Despite excellent inter-observer agreement, the Sgarbossa criteria is too insensitive to be implemented in clinical practice as it cannot be relied upon to identify correctly, patients who have suffered AMI. Instead, diagnosis and management should proceed according to clinical judgement with reperfusion therapy administered following evaluation of risk verses benefit.
A9 Temperature variation in pre hospital environments
Authors: Black S , Allen K
Published: October 2011

Introduction

Research from outside the UK has demonstrated that the temperature variation experienced in pre hospital emergency vehicles can exceed the recommended limits of drug companies and may be outside the operating restrictions set down by medical device manufacturers. This study aimed to engage ambulance clinicians in research by participating in a longitudinal study measuring the temperature in a variety of emergency service vehicles and mediation storage facilities. The study used data loggers capable of recording temperatures up to extreme levels at routine intervals. These were placed in variety of environments to monitor the temperature variation in both pre hospital vehicles and static sites such as drug cupboards.

Methods

Measurement was phased over 2 years, covering both the summer and winter periods to capture seasonal differences in the minimum and maximum temperatures experienced. Data loggers were placed in a range of vehicles, from emergency ambulances to rapid response cars where the location of drug storage facilities differ. Comparisons are drawn between vehicles which spent time garaged and those that were not. Temperature loggers were placed within ambulance drug bags and also attached to equipment housing within the vehicle to establish the temperature variation which may affect the operation of medical devices.

Results

Results show a wide variation in temperatures, from −7.5°C to over 30°C some of which were sustained for periods of several hours. More variation was observed in vehicles than in static sites such as station drug stores.

Conclusion

Although this project did not look at the pharmacological degradation of emergency drugs, the variation in temperature found has implications which may impact on the efficacy of pre hospital medications and for the operating efficiency of medical devices.
Can data collected from marine protected areas improve estimates of life-history parameters?
Authors: Garrison Thomas M. , Hamel Owen S. , Punt André E.
Published: October 2011

One of the argued research-related benefits of marine protected areas (MPAs) to fisheries management is that because there is no fishing inside of an MPA, it may be possible to precisely estimate the rate of natural mortality and better determine growth and maturity rates, parameters that are often prespecified in stock assessments. This study assesses the degree to which having an MPA increases the ability to estimate these parameters in a integrated stock assessment model, Stock Synthesis; how long it would take for these benefits to be reflected in improved estimates of management quantities; and the extent to which these improvements will be reduced or lost if there is movement of adults (i.e., spillover) from the MPA to the fished area. A two-area, age- and length-structured simulation model is used to examine these benefits on estimation performance for Stock Synthesis. Given the data and process assumptions explored here, the extent of improvement in estimation of growth and maturity parameters with data collected from MPAs is small, but estimation of natural mortality is substantially improved compared with directly estimating these parameters using fishery data. The extent of this improvement depends on the degree of spillover and the complexity of the assessment model.
Skeletal muscle apoptotic response to physical activity: potential mechanisms for protection
Authors: Quadrilatero Joe , Alway Stephen E. , Dupont-Versteegden Esther E.
Published: October 2011

Apoptosis is a highly conserved type of cell death that plays a critical role in tissue homeostasis and disease-associated processes. Skeletal muscle is unique with respect to apoptotic processes, given its multinucleated morphology and its apoptosis-associated differences related to muscle and (or) fiber type as well as mitochondrial content and (or) subtype. Elevated apoptotic signaling has been reported in skeletal muscle during aging, stress-induced states, and disease; a phenomenon that plays a role in muscle dysfunction, degradation, and atrophy. Exercise is a strong physiological stimulus that can influence a number of extracellular and intracellular signaling pathways, which may directly or indirectly influence apoptotic processes in skeletal muscle. In general, acute strenuous and eccentric exercise are associated with a proapoptotic phenotype and increased DNA fragmentation (a hallmark of apoptosis), whereas regular exercise training or activity is associated with an antiapoptotic environment and reduced DNA fragmentation in skeletal muscle. Interestingly, the protective effect of regular activity on skeletal muscle apoptotic processes has been observed in healthy, aged, stress-induced, and diseased rodent models. Several mechanisms for this protective response have been proposed, including altered anti- and proapoptotic protein expression, increased mitochondrial biogenesis and improved mitochondrial function, and reduced reactive oxygen species generation and (or) enhanced antioxidant status. Given the current literature, we propose that regular physical activity may represent an effective strategy to decrease apoptotic signaling, and possibly muscle wasting and dysfunction, during aging and disease.
Forearm muscle size, strength, force, and power in relation to pQCT-derived bone strength at the radius in adults
Authors: Lorbergs Amanda L. , Farthing Jonathan P. , Baxter-Jones Adam D.G. , Kontulainen Saija A.
Published: October 2011

We aimed to examine the relationship between forearm muscle cross-sectional area (MCSA), muscle force, or rate of torque development (RTD) and 2 estimated radius bone strength indices — compressive bone strength index (BSI) at the wrist and strength strain index in torsion (SSIp) at the shaft — in healthy middle-aged males and females. Distal (4%) and shaft (65%) sites of nondominant forearms were scanned using peripheral quantitative computed tomography (pQCT) in a sample of 48 adults (mean age ± SD, 49.4 ± 2.4 y) to obtain estimated bone strength indices and MCSA. Muscle force, measured by grip dynamometry and wrist flexion RTD, was obtained using an isokinetic dynamometer. Hierarchical linear regressions, adjusted for weight, explained 27% and 36% of the BSI variance at the 4% site in males and premenopausal females, respectively (p < 0.05). At the radius shaft, weight explained 26% (p < 0.05) and 83% (p < 0.01) of SSIp variance. The unique variance of BSI explained by MCSA was 16% in males (p < 0.05) and 31% in females (p < 0.01). Grip force predicted variance in SSIp in males (p < 0.01) and BSI in females (p < 0.05). RTD did not explain any variance in BSI or SSIp. Body weight was the only significant predictor (p < 0.05) of SSIp in females. Although forearm muscle size and grip strength are associated with estimates of radius bone strength at midlife, this relationship appears to be sex dependent. The differences observed between muscle size and strength properties and bone strength at distal and shaft sites of the radius suggest a property-, sex-, and site-specific relationship between muscle and bone in the forearm.
Deacetylation of PGC-1α by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis
Authors: Gurd Brendon J.
Published: October 2011

Activation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-mediated transcription is important for both the determination of mitochondrial content and the induction of mitochondrial biogenesis in skeletal muscle. SIRT1 (silent mating type information regulator 2 homolog 1) deactetylation is proposed as a potential activator of PGC-1α transcriptional activity. The current review examines the importance of SIRT1 deacetylation of PGC-1α in skeletal muscle. Models of SIRT1 overexpression and pharmacological activation are examined, but changes in SIRT1 expression and deacetylase activity following acute and chronic contractile activity will be emphasized. In addition, potential mechanisms of SIRT1 activation in skeletal muscle will be examined. The importance of the PGC-1α acetyltransferase GCN5 will also be briefly discussed. The current evidence supports the contribution of SIRT1 deacetylation of PGC-1α to exercise-induced mitochondrial biogenesis. Further research examining exercise-mediated activation of SIRT1 and the role of GCN5 in regulating PGC-1α transcriptional activity in skeletal muscle is required.
Functional analysis of the human concentrative nucleoside transporter-1 variant hCNT1S546P provides insight into the sodium-binding pocket
Authors: Cano-Soldado Pedro , Gorraitz Edurne , Errasti-Murugarren Ekaitz , Casado F. Javier , Lostao M. Pilar , Pastor-Anglada Marçal
Published: October 2011

SLC28 genes, encoding concentrative nucleoside transporter proteins (CNT), show little genetic variability, although a few single nucleotide polymorphisms (SNPs) have been associated with marked functional disturbances. In particular, human CNT1S546P had been reported to result in negligible thymidine uptake. In this study we have characterized the molecular mechanisms responsible for this apparent loss of function. The hCNT1S546P variant showed an appropriate endoplasmic reticulum export and insertion into the plasma membrane, whereas loss of nucleoside translocation ability affected all tested nucleoside and nucleoside-derived drugs. Site-directed mutagenesis analysis revealed that it is the lack of the serine residue itself responsible for the loss of hCNT1 function. This serine residue is highly conserved, and mutation of the analogous serine in hCNT2 (Ser541) and hCNT3 (Ser568) resulted in total and partial loss of function, respectively. Moreover, hCNT3, the only member that shows a 2Na+/1 nucleoside stoichiometry, showed altered Na+ binding properties associated with a shift in the Hill coefficient, consistent with one Na+ binding site being affected by the mutation. Two-electrode voltage-clamp studies using the hCNT1S546P mutant revealed the occurrence of Na+ leak, which was dependent on the concentration of extracellular Na+ indicating that, although the variant is unable to transport nucleosides, there is an uncoupled sodium transport.
Transgenic hCFTR expression fails to correct β-ENaC mouse lung disease
Authors: Grubb B. R. , O'Neal W. K. , Ostrowski L. E. , Kreda S. M. , Button B. , Boucher R. C.
Published: October 2011

The relationships between airway epithelial Cl− secretion-Na+ absorption balance, airway surface liquid (ASL) homeostasis, and lung disease were investigated in selected transgenic mice. 1) To determine if transgenic overexpression of wild-type (WT) human CFTR (hCFTR) accelerated Cl− secretion and regulated Na+ absorption in murine airways, we utilized a Clara cell secretory protein (CCSP)-specific promoter to generate mice expressing airway-specific hCFTR. Ussing chamber studies revealed significantly (∼2.5-fold) elevated basal Cl− secretory currents in CCSP-hCFTR transgenic mouse airways. Endogenous murine airway Na+ absorption was not regulated by hCFTR, and these mice exhibited no lung disease. 2) We tested whether hCFTR, transgenically expressed on a transgenic mouse background overexpressing the β-subunit of the epithelial Na+ channel (β-ENaC), restored ion transport balance and ASL volume homeostasis and ameliorated lung disease. Both transgenes were active in CCSP-hCFTR/β-ENaC transgenic mouse airways, which exhibited an elevated basal Cl− secretion and Na+ hyperabsorption. However, the airway disease characteristic of β-ENaC mice persisted. Confocal studies of ASL volume homeostasis in cultured tracheal cells revealed ASL autoregulation to a height of ∼6 μm in WT and CCSP-hCFTR cultures, whereas ASL was reduced to <4 μm in β-ENaC and CCSP-hCFTR/β-ENaC cultures. We conclude that 1) hCFTR overexpression increases basal Cl− secretion but does not regulate Na+ transport in WT mice and 2) transgenic hCFTR produces increased Cl− secretion, but not regulation of Na+ channels, in β-ENaC mouse airways and does not ameliorate β-ENaC mouse lung disease.
Influence of a single loading episode on gene expression in healing rat Achilles tendons
Authors: Eliasson Pernilla , Andersson Therese , Aspenberg Per
Published: October 2011

Mechanical loading stimulates tendon healing via mechanisms that are largely unknown. Genes will be differently regulated in loaded healing tendons, compared with unloaded, just because of the fact that healing processes have been changed. To avoid such secondary effects and study the effect of loading per se, we therefore studied the gene expression response shortly after a single loading episode in otherwise unloaded healing tendons. The Achilles tendon was transected in 30 tail-suspended rats. The animals were let down from the suspension to load their tendons on a treadmill for 30 min once, 5 days after tendon transection. Gene expression was studied by Affymetrix microarray before and 3, 12, 24, and 48 h after loading. The strongest response in gene expression was seen 3 h after loading, when 150 genes were up- or downregulated (fold change ≥2, P ≤ 0.05). Twelve hours after loading, only three genes were upregulated, whereas 38 were downregulated. Fewer than seven genes were regulated after 24 and 48 h. Genes involved in the inflammatory response were strongly regulated at 3 and 12 h after loading; this included upregulation of iNOS, PGE synthase, and IL-1β. Also genes involved in wound healing/coagulation, angiogenesis, and production of reactive oxygen species were strongly regulated by loading. Microarray results were confirmed for 16 selected genes in a repeat experiment ( N = 30 rats) using real-time PCR. It was also confirmed that a single loading episode on day 5 increased the strength of the healing tendon on day 12. In conclusion, the fact that there were hardly any regulated genes 24 h after loading suggests that optimal stimulation of healing requires a mechanical loading stimulus every day.
Determinants of arterial gas embolism after scuba diving
Authors: Ljubkovic Marko , Zanchi Jaksa , Breskovic Toni , Marinovic Jasna , Lojpur Mihajlo , Dujic Zeljko
Published: October 2011

Scuba diving is associated with breathing gas at increased pressure, which often leads to tissue gas supersaturation during ascent and the formation of venous gas emboli (VGE). VGE crossover to systemic arteries (arterialization), mostly through the patent foramen ovale, has been implicated in various diving-related pathologies. Since recent research has shown that arterializations frequently occur in the absence of cardiac septal defects, our aim was to investigate the mechanisms responsible for these events. Divers who tested negative for patent foramen ovale were subjected to laboratory testing where agitated saline contrast bubbles were injected in the cubital vein at rest and exercise. The individual propensity for transpulmonary bubble passage was evaluated echocardiographically. The same subjects performed a standard air dive followed by an echosonographic assessment of VGE generation (graded on a scale of 0–5) and distribution. Twenty-three of thirty-four subjects allowed the transpulmonary passage of saline contrast bubbles in the laboratory at rest or after a mild/moderate exercise, and nine of them arterialized after a field dive. All subjects with postdive arterialization had bubble loads reaching or exceeding grade 4B in the right heart. In individuals without transpulmonary passage of saline contrast bubbles, injected either at rest or after an exercise bout, no postdive arterialization was detected. Therefore, postdive VGE arterialization occurs in subjects that meet two criteria: 1) transpulmonary shunting of contrast bubbles at rest or at mild/moderate exercise and 2) VGE generation after a dive reaches the threshold grade. These findings may represent a novel concept in approach to diving, where diving routines will be tailored individually.
X-ray powder diffraction data of layered cobaltites with the compositions Ca3−xSrxCo4O9
Authors: Yoon Sejin , Kwon O-Jong , Jung Myung-Jin , Yoo Jaeun , Park Chan , Chae Keun Hwa
Published: October 2011

Ca3−xSrxCo4O9 with different compositions (x=0, 0.15, 0.3, and 0.45) were synthesized from stoichiometric mixtures of Co3O4, CaCO3, and SrCO3, and their unit-cell parameters were determined. The powders were mixed with silicon standard powder, and XRD patterns were collected and analyzed using TOPAS. The compounds were determined to be monoclinic with space group of P2. Unit-cell parameters changed from a=4.8329(3) Å, b=4.5727(1) Å, c=10.8360(4) Å, and β=98.093(7)° when x=0, to a=4.8432(1) Å, b=4.6100(3) Å, c=10.8668(3) Å, and β=98.110(5)° when x=0.3. An unidentified second phase was observed when x=0.45.
X-ray powder diffraction data for a new succinylcholine iodide polymorph, 2,2′-[(1,4-dioxobutane-1,4-diyl)bis(oxy)] bis(N,N,N-trimethyl-ethanaminium) iodide
Authors: Pažout R. , Maixner J. , Cibulková J. , Kratochvíl B.
Published: October 2011

X-ray powder diffraction data, unit-cell parameters, and space group for a new succinylcholine iodide polymorph II, C14H30O4N2I2, are reported [a=13.908(3) Å, b=13.184(3) Å, c=11.717(2) Å, β=92.501(3)°, unit-cell volume V=2146,28 Å3, Z=4, space group P21/c]. All measured lines with the exception of one were indexed and are consistent with the P21/c space group. No detectable impurities were observed.
Brentuximab Vedotin (SGN-35)
Authors: Katz Jessica , Janik John E. , Younes Anas
Published: October 2011

Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) directed against the CD30 antigen expressed on Hodgkin lymphoma and anaplastic large cell lymphoma. SGN-35 consists of the cAC10 chimerized IgG1 monoclonal antibody SGN30, modified by the addition of a valine-citrulline dipeptide linker to permit attachment of the potent inhibitor of microtubule polymerization monomethylauristatin E (MMAE). In phase II trials, SGN-35 produced response rates of 75% in patients with Hodgkin lymphoma (n = 102) and 87% in patients with anaplastic large cell lymphoma (n = 30). Responses to SGN-35 might be related not only to the cytotoxic effect due to release of MMAE within the malignant cell but also to other effects. First, SGN-35 may signal malignant cells through CD30 ligation to deliver an apoptotic or proliferative response. The former would amplify the cytotoxicity of MMAE. A proliferative signal delivered in the context of MMAE intoxication could enhance cell death. Second, the efficacy of SGN-35, particularly in Hodgkin lymphoma, might be attributed to its effect on the tumor microenvironment. Diffusion of free MMAE from the targeted tumor cells could result in a bystander effect that kills the normal supporting cells in close proximity to the malignant cells. The elimination of T regulatory cells that inhibit cytotoxic effector cells and elimination of cells that provide growth factor support for Hodgkin/Reed–Sternberg cells could further enhance the cytotoxic activity of SGN-35. Here we review the biology of SGN-35 and the clinical effects of SGN-35 administration. Clin Cancer Res; 17(20); 6428–36. ©2011 AACR.
Polo-like Kinase 1 Inhibitors and Their Potential Role in Anticancer Therapy, with a Focus on NSCLC
Authors: Medema René H. , Lin Chia-Chi , Yang James Chih-Hsin
Published: October 2011

Cytotoxic platinum-doublet chemotherapy that includes antimitotic agents is a current standard of care in advanced non–small cell lung cancer (NSCLC). Microtubule-targeting antimitotics, taxanes, and Vinca alkaloids are effective anticancer therapeutics that affect both dividing and nondividing cells. A new generation of antimitotic agents that target regulatory proteins—mitotic kinases and kinesins—has the potential to overcome the limitations related to the role of tubulin in nondividing cells that are associated with traditional antimitotics. This review concentrates on Polo-like kinase 1, a key regulator of mitosis, outlines a rationale for its development as an anticancer target, and discusses data from preclinical and clinical studies of Plk1 inhibitors with a particular focus on NSCLC. Clin Cancer Res; 17(20); 6459–66. ©2011 AACR.
Trastuzumab Emtansine: A Unique Antibody-Drug Conjugate in Development for Human Epidermal Growth Factor Receptor 2–Positive Cancer
Authors: LoRusso Patricia M. , Weiss Denise , Guardino Ellie , Girish Sandhya , Sliwkowski Mark X.
Published: October 2011

Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor (HER2)–targeted antibody-drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine), in phase III development for HER2-positive cancer. Extensive analysis of T-DM1 in preclinical studies has shown that T-DM1 combines the distinct mechanisms of action of both DM1 and trastuzumab, and has antitumor activity in trastuzumab- and lapatinib-refractory experimental models. Clinically, T-DM1 has a consistent pharmacokinetics profile and minimal systemic exposure to free DM1, with no evidence of DM1 accumulation following repeated T-DM1 doses. Although a few covariates were shown to affect interindividual variability in T-DM1 exposure and clearance in population-pharmacokinetics analyses, the magnitude of their effect on T-DM1 exposure was not clinically relevant. Phase I and phase II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are recruiting patients: EMILIA (NCT00829166) is evaluating T-DM1 compared with lapatinib plus capecitabine, and MARIANNE (NCT01120184) is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Additional combinations of T-DM1 (for example, with GDC-0941) and additional disease settings (early-stage HER2-positive breast cancer) are also under investigation. Data from the phase III trials and other studies of T-DM1–containing agents are eagerly awaited. Clin Cancer Res; 17(20); 6437–47. ©2011 AACR.
Ileal Pouch Anal Anastomosis with Close Rectal Dissection Using Automated Vessel Sealers for Ulcerative Colitis: A Promising Alternative
Authors: de Zeeuw Sharonne , Ahmed Ali Usama , van der Kolk Marion B.M. , van Laarhoven Kees C.J.H.M.
Published: October 2011

Background: Despite decennia of experience, ileal pouch anal anastomosis for ulcerative colitis is still associated with high complication rates. The development of automatic vessel sealers has resulted in the revival of a promising surgical alternative to the conventional procedure: close rectal dissection. By preserving the mesorectal layer it is hypothesized that nerve-related and other postoperative complications can be reduced. Methods: All patients with ulcerative colitis with indication for restorative proctocolectomy at our institution during the pilot study underwent the close rectal pouch procedure with temporary diverting ileostomy. Standardized clinical history, anorectal physiology measurements, and endoscopic and histological examination were carried out before and after surgery. Results: The procedure was technically successful in all 10 patients, with a median age of 41 years and a median postoperative follow-up period of 16 months. There were no cases of pelvic sepsis and bladder or sexual dysfunction. The median daytime defecation frequency was 6.0. Endoscopic and histological examination showed no abnormalities. The anorectal physiology supported the good functional results. Conclusion: The preliminary results of the close rectal pouch procedure are promising, with good functional results and a low complication rate after 1 year.
Current Application of Selective Decontamination of the Digestive Tract, Perioperative Antibiotics and Mechanical Bowel Preparation in Surgical Departments in the Netherlands
Authors: Mutsaers S.N. , Roos D. , Oudemans-van Straaten H.M. , de Wit L.T. , Gouma D.J. , Gerhards M.F.
Published: October 2011

Objective:To study the current application of selective decontamination of the digestive tract (SDD), the use of preoperative antibiotics and mechanical bowel preparation (MBP) in elective gastrointestinal (GI) surgery in surgical departments in the Netherlands. Methods:A point prevalence survey was carried out and an online questionnaire was sent to GI surgeons of 86 different hospitals. Results:The response rate was 74%. Only 4/64 (6.3%) of the Dutch surgical wards are currently using perioperative SDD as a prophylactic strategy to prevent postoperative infectious complications. The 4 hospitals using SDD on their surgical wards also use it on their ICUs. All hospitals make use of perioperative intravenous antibiotic prophylaxis in elective GI surgery. In most hospitals, a cephalosporin and metronidazole are applied (81.3 and 76.6%). MBP was used in 58 hospitals (90.6%) mainly in left colonic surgery. Conclusions: Perioperative SDD is rarely used in elective GI surgery in the Netherlands. Perioperative intravenous antibiotic prophylaxis is given in all Dutch hospitals, conforming to guidelines. Although the recent literature does not recommend MBP before surgery, it is still selectively used in 90.6% of the Dutch surgical departments, mainly in open or laparoscopic left colonic surgery (including sigmoid resections).
Derivation of Smooth Muscle Cells with Neural Crest Origin from Human Induced Pluripotent Stem Cells
Authors: Wang Aijun , Tang Zhenyu , Li Xian , Jiang Yisu , Tsou Danielle A. , Li Song
Published: October 2011

The heterogeneity of vascular smooth muscle cells (SMCs) is related to their different developmental origins such as the neural crest and mesoderm. Derivation of SMCs from different origins will provide valuable in vitro models for the investigation of vascular development and diseases. From the perspective of regenerative medicine and tissue engineering, an expandable cell source of SMCs is required for the construction of tissue-engineered blood vessels. In this study, we developed a robust protocol to derive neural crest stem cells (NCSCs) from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). NCSCs derived from ESCs and iPSCs were expandable with similar cell doubling times. NCSCs were capable of differentiating into neural and mesenchymal lineages. TGF-β1 induced the expression of SMC markers calponin-1, SM22α, and smooth muscle myosin heavy chain and resulted in the assembly of smooth muscle α-actin, calponin-1, and SM22α into stress fibers. This work provides a basis for using iPSCs to study SMC biology and deriving vascular cells for tissue engineering.
Additional Chromosome Abnormalities, BCR-ABL Tyrosine Kinase Domain Mutations and Clinical Outcome in Hungarian Tyrosine Kinase Inhibitor-Resistant Chronic Myelogenous Leukemia Patients
Authors: Meggyesi Nóra , Kozma András , Halm Gabriella , Nahajevszky Sarolta , Bátai Árpád , Fekete Sándor , Barta Anikó , Ujj György , Lueff Sándor , Sipos Andrea , Ádám Emma , Bors András , Reményi Péter , Masszi Tamás , Tordai Attila , Andrikovics Hajnalka
Published: October 2011

Background: Additional chromosome abnormalities (ACAs), mutations of the BCR-ABL tyrosine kinase domain (TKD) and BCR-ABL splice variants may cause resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myelogenous leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoid leukemia (ALL). Methods: Karyotyping and BCR-ABL TKD mutation screening were performed in 71 imatinib-resistant CML patients and 6 Ph+ ALL patients. A total of 56 out of these 77 patients received second-generation TKI. Results: ACAs were present in 30 of 65 imatinib-resistant patients (46%). In 27 of 74 imatinib-resistant patients (36%), 15 different BCR-ABL TKD mutations were detected. Mutations were found in 25% of chronic-phase patients (12/47), 33% of accelerated-phase patients (5/15), 71% of blast crisis CML patients (5/7) and 100% of ALL patients. In nilotinib-resistant patients, Y253H, T315I and F359I/V mutations were detected; in dasatinib-resistant patients, L248M, E279K and T315I mutations were detected. T315I was found more frequently in patients on dasatinib than on imatinib therapy. The presence of ACAs predicted shorter survival during first- and second-generation TKI therapy, while TKD mutations only influenced survival during second-generation TKI therapy. Conclusion: For patients with TKI resistance, mutation and ACA screening may play a role in identifying patients with poorer prognosis.
A New Landscape for Stroke Prevention in Atrial Fibrillation
Authors: Banerjee Amitava , Marín Francisco , Lip Gregory Y.H.
Published: October 2011

Background—

Worldwide, atrial fibrillation is the most common arrhythmia, and its symptoms and sequelae cause an enormous burden to patients and health systems. Stroke is associated with the greatest mortality and morbidity in patients with atrial fibrillation (AF). The last decade has seen great advances in scientific and therapeutic approaches to AF.

Purpose—

This review considers recent changes to stroke prevention, particularly focusing on new anticoagulants, antiarrhythmic drugs, and devices as well as future research directions.

Summary of Review—

A semi-systematic literature review was performed using search terms “atrial fibrillation” and “novel therapy” within the PubMed database from 2005 to 2011. The area of greatest progress has been novel anticoagulants with direct thrombin inhibitors and factor Xa inhibitors. Dabigatran is the only novel agent currently licensed for use in AF patients, but with several trials of novel agents pending and favorable results so far, other agents are likely to follow. Novel antiarrhythmic drugs, left atrial appendage occlusion, and upstream therapies all represent potential new approaches but require further research.

Conclusions—

Novel anticoagulant and arrhythmic agents are changing treatment guidelines and choices available to both patients and clinicians for stroke prevention in AF, but bring new considerations and long-term data are required, because most patients will require lifelong therapy. Future research must incorporate patient values and preferences, because novel therapies can potentially give very different treatment options, which must be explained for patients to make informed choices.
Transthoracic Echocardiography to Rule Out Paroxysmal Atrial Fibrillation as a Cause of Stroke or Transient Ischemic Attack
Authors: Stahrenberg Raoul , Edelmann Frank , Haase Beatrice , Lahno Rosine , Seegers Jochen , Weber-Krüger Mark , Mende Meinhard , Wohlfahrt Janin , Kermer Pawel , Vollmann Dirk , Hasenfuß Gerd , Gröschel Klaus , Wachter Rolf
Published: October 2011

Background and Purpose—

We assessed whether echocardiography can predict paroxysmal atrial fibrillation (PAF) in patients with cerebral ischemia presenting in sinus rhythm.

Methods—

Within the prospective Find-AF cohort, 193 consecutive patients with cerebral ischemia and sinus rhythm on presentation had evaluation of echocardiographic parameters of left atrial size and function. PAF was diagnosed by 7-day Holter monitoring.

Results—

In 26 patients with PAF, late diastolic Doppler (A) and tissue Doppler (a′) velocities were lower whereas left atrial diameter, left atrial volume index (LAVI), LAVI/A, and LAVI/a′ were larger (
P
<0.05 for all) than they were in 167 patients without PAF. In multivariate models A, a′, LAVI/A, and LAVI/a′ predicted the presence of PAF. Area under the receiver operating characteristic curve to diagnose PAF was highest for LAVI/a′ (0.813 [0.738; 0.889]). A previously suggested cut-off of LAVI/a′ <2.3 had 92% sensitivity, 55.8% specificity, and 98% negative predictive value for PAF.

Conclusions—

LAVI/a′ <2.3 can effectively rule out PAF in patients with cerebral ischemia.
Juvenile Penalties for “Lawyering Up”
Authors: Armstrong Gaylene S. , Kim Bitna
Published: October 2011

The presence of counsel for juveniles in the courtroom seems advantageous from a due process perspective, yet some studies suggest that juveniles receive harsher dispositions when represented by an attorney. This study tested whether a “counsel penalty” existed regardless of attorney type and, guided by prior sentencing literature, used a more comprehensive model to determine the influence of extralegal and contextual factors that may amplify the counsel penalty. Utilizing official data from a Northeastern state in a multilevel modeling strategy, this study found that regardless of the type of counsel retained, harsher sentences were received as compared with cases in which a juvenile was not represented by counsel even after controlling for offense type. Moreover, minority youth with public defenders and males with private counsel received harsher sentences while community characteristics did not appear to have a significant influence on sentencing decisions.
Comorbid social withdrawal (hikikomori) in outpatients with social anxiety disorder: Clinical characteristics and treatment response in a case series
Authors: Nagata Toshihiko , Yamada Hisashi , Teo Alan R. , Yoshimura Chiho , Nakajima Takenori , van Vliet Irene
Published: October 2011

Background:

Severe social withdrawal (called hikikomori, and defined as isolation lasting more than six months and not due to an apparent mental disorder) has drawn increasing public attention in Japan. It is unclear whether hikikomori is merely a symptom or syndrome of social withdrawal.

Aim:

To evaluate this phenomenon in relationship to social anxiety disorder (SAD), as few previous studies have.

Methods:

One hundred and forty-one consecutive patients with SAD diagnosed according to DSM-IV criteria by a semi-structured interview were treated with a combination of psychotherapy, pharmacotherapy and group activity.

Results:

Twenty-seven (19%) SAD patients fulfilled the criteria for hikikomori, and these patients had earlier onset, more symptoms and less education than non- hikikomori SAD patients. Only 33% of hikikomori SAD patients spontaneously complained of SAD symptoms at first visit. There were no diagnostic differences between hikikomori and non- hikikomori SAD patients, except that comorbid obsessive–compulsive disorder was more frequent in hikikomori SAD patients. Functional impairment in 10 (37%) hikikomori SAD patients improved after several years of combination therapy.

Conclusion:

Hikikomori may serve as a proxy for a severe form of SAD. Patients with comorbid SAD and hikikomori have lower treatment response rates than those with SAD alone.
Risky Business: How Professionals and Professional Fields (Must) Deal with Organizational Issues
Authors: Noordegraaf Mirko
Published: October 2011

As professionals belong to occupational systems but also increasingly work inside organizations, new linkages between occupational and organizational domains are required, but they are difficult to develop. Occupational principles and professional standards are usually considered to be at odds with managerial and organizational control principles. This generates academic and practical dualisms. Either a return to professionalism is advocated in order to protect occupational spaces and ‘rescue’ professional work, or there is a move beyond professionalism in order to restrict autonomies and discipline professional work. This article argues that both stances are unsatisfactory and that new forms of organized professionalism are called for. Changing circumstances force professional services to respond to external changes that call for organizational capacities, also inside professional domains: (a) professionals develop new work preferences and seek organized work conditions; (b) professionals face new cases, which are difficult to categorize and call for well-organized multi-professional acts; (c) due to critical attention for case treatment and incidents, professionals face new risks that have to be managed. The article shows how these realities are incorporated in professional practices – albeit slowly – and it draws normative conclusions. Professionals must take organizing and managing more seriously and will have to develop organizational capacities. In addition, connective organizational standards must be established in order to strengthen the viability and legitimacy of professional services in demanding times.
A Market for Weather Risk? Conflicting Metrics, Attempts at Compromise, and Limits to Commensuration
Authors: Huault Isabelle , Rainelli-Weiss Hélène
Published: October 2011

In this paper, we examine the process of risk commodification involved in the creation of a market for weather derivatives in Europe. We approach this issue through an in-depth qualitative study in which we focus on the commensuration process by which promoters try to draw weather risk into the financial world. By offering a concrete description of a derivatives market as a meeting place between different metrics, our results highlight the failure of a process of commensuration – a phenomenon rarely studied empirically in the literature – and its unexpected results. Compared to existing research, we use the theoretical framework provided by Boltanski and Thévenot (2006) to enrich the literature on commensuration specifically as regards the different forms of agreement to which commensuration attempts can lead. Our results highlight the crucial role of a common interest for commensuration to succeed, and the conditions necessary for this common interest to occur. We conclude that there are limits to the thesis of financial theory, according to which all kinds of risk can be transformed into financial risk, and exchanged on financial markets.
Individual and country-level factors affecting support for foreign aid
Authors: Paxton Pamela , Knack Stephen
Published: October 2011

The determinants of public opinion on foreign aid in donor countries have received little attention. This paper examines support for foreign aid with a large, multi-level, cross-national study. Hypotheses are tested with multi-level models, including both individual-level and country-level variables, to predict positive attitudes. Two datasets are used to measure attitudes in donor countries: (1) the 1995 World Values Survey, which has information from approximately 6,000 individuals in nine countries and asks a rich battery of questions at the individual level; (2) the 2002 Gallup Voice of the People survey, asks fewer questions of individuals but contains 17 donor countries. Using both surveys combines their distinct strengths and allows tests of individual- and national-level theories across disparate samples. Results generally support the predictions that attitudes toward aid are influenced by religiosity, beliefs about the causes of poverty, awareness of international affairs, and trust in people and institutions.
Political attitudes and political participation: A panel study on socialization and self-selection effects among late adolescents
Authors: Quintelier Ellen , Hooghe Marc
Published: October 2011

The expectation that participation entails socialization effects on political attitudes is not routinely tested in a longitudinal manner. In this article, we report on a two-year panel study among 4325 late adolescents in Belgium. By means of a cross-lagged structural equation model, it was ascertained that the relationship between participation and attitudes is reciprocal. The relationship between participation (at Time1) and attitudes (at Time2) was significantly stronger than the relationship between attitudes (at Time1) and participation (at Time2). Therefore, the current study supports the socialization perspective. Individual and collective forms of participation have equally strong socialization effects.
Evaluation of Factors Concerning the Olfaction Using the Sniffin’ Sticks Test
Authors: Orhan Kadir Serkan , Karabulut Burak , Keleş Nesil , Değer Kemal
Published: October 2011

Objective

This study aimed to research the normative values of olfactory function in the Turkish population using the Sniffin’ Sticks test and to relate olfactory performance to age, sex, smoking, educational level, and the side examined. It also aimed to compare the results with other countries’ normative values, especially Europe, using the same test and procedure.

Study Design

Prospective clinical study.

Setting

Tertiary referral center.

Subjects and Methods

This study was a prospective clinical trial conducted in a tertiary clinic. A total of 100 healthy subjects were included in the study. Of these, 50 were men and 50 were women. The mean (SD) age of the subjects was 37.7 (14.8) years (range, 18‐77 years).

Results

Odor scores were lower than the scores of other countries, and the scores decreased significantly with age. There was no relationship between olfaction and sex or smoking. Subjects with a lower educational status had lower scores compared with the scores of median and highly educated subjects.

Conclusion

This is the first study that evaluated the relationship between education level and olfaction. According to the results, the cultural differences, education level, and age seemed to influence odor scores. The Sniffin’ Sticks test can be used to assess olfactory performance in a Turkish population, but identification of odors in this test battery may show variability because of local and cultural factors.