bluuebunny/crossref_metadata_2025 huggingface dataset:
Topiramate in Children With West Syndrome: A Retrospective Multicenter Evaluation of 100 Patients
Authors: Korinthenberg Rudolf , Schreiner Andreas
Published: May 2007

The aim of this study is to investigate the efficacy and tolerability of topiramate in a large number of children with West syndrome. The authors performed a retrospective, questionnaire-based data collection in specialized epilepsy units in Germany. Patients with West syndrome and hypsarrhythmia could be included if topiramate treatment had started at an age of ≤3 years. Data of 100 patients were evaluated. Nearly all patients were severely affected and had been treated with multiple antiepileptic drugs with insufficient effect. Topiramate was introduced at a median age of 11.9 months. The median starting dosage was 1.6 mg/kg body weight per day, increased to a median maximum dosage of 12.0 mg/kg. Sixty-one patients received between 1 and 3 antiepileptic drugs in addition to topiramate. The median daily dose considered by the attending physicians to be most effective regarding seizure reduction was 10 mg/kg. A significant reduction in the number of seizures per week was achieved. A total of 17.5% of patients became free of seizures, and in 47%, the seizure frequency decreased by at least 50%. Hypsarrhythmia or status-like electroencephalography patterns remitted in 18 of 83 cases. Side effects were reported in 25% of children and included mostly sedation, loss of appetite, weight loss, and metabolic acidosis. These side effects were statistically related to the number of additional antiepileptic drugs but not to the topiramate dosage. In 17% of patients, topiramate treatment was discontinued because of side effects and in a further 4% because of worsening of seizures. In 44% of patients, treatment was continued for more than 3 months. In conclusion, the data suggest that topiramate is a useful drug in treating West syndrome. However, because of the inherent limitations of the retrospective study design, future prospective controlled studies should be performed.
Representation in Nonprofit and Voluntary Organizations: A Conceptual Framework
Authors: Chao Guo  , Musso Juliet A.
Published: May 2007

It is held that nonprofit and voluntary organizations contribute to democratic governance by representing the interests of their constituents to the state. Yet little is known about the capacities of these organizations to represent effectively their constituents and the larger community. This study proposes a framework for understanding the varieties of representation in nonprofit and voluntary organizations. The authors argue that the nature of representation within an organization is indicated by five dimensions: substantive, symbolic, formal, descriptive, and participatory representation. Formal, descriptive, and participatory representation are different means of achieving substantive and symbolic representation; the latter being measures of the extent to which organizations “act for” and “stand for” particular constituencies. They further suggest that this conceptual framework serves as a useful first step toward examining the representational capacities of nonprofit organizations. Two illustrative cases of community-based organizations are presented to tease out the complexity of representational mixes found in nonprofits.
An Investigation of Innovation in Nonprofit Organizations: The Role of Organizational Mission
Authors: McDonald Robert E.
Published: May 2007

Nonprofit organizations are experiencing increasing pressures to be more business-like and to focus on financial outcomes for sustainability and growth. There have been questions whether this attention on performance might come at the cost of serving an organization's mission. The research presented here indicates that a nonprofit organization's mission can facilitate innovation, which has been shown to be a key mediating step in achieving superior organizational performance. Two studies were conducted among nonprofit hospitals in the United States to investigate the role of the nonprofit organization's mission in the innovation process. The findings indicate that a clear, motivating organizational mission helps an organization to focus its attention on those innovations that will most likely support the accomplishment of that mission. Such a mission also creates a climate in which innovations are given a fair chance to succeed. As a result, firms with clear, motivating missions tend to be more innovative.
The Relationship Among Organizational-Based Self-Esteem and Various Factors Motivating Volunteers
Authors: Mayer Brad W. , Fraccastoro Katherine A. , McNary Lisa D.
Published: May 2007

Organizational-based self-esteem (OBSE) reflects the perception individuals have of themselves as important, meaningful, effectual, and worthwhile within their organization. Employees with high OBSE participate in activities valued by their organization and in other organization-related behaviors that will benefit the organization to display organizational citizenship behavior (OCB). The purpose of this study is to examine the effect of OBSE on the extent of voluntarism and the perceived motives behind why individuals volunteer. Using survey research, this study tested eight hypotheses and found six relating OBSE to the amount of time volunteered and the reasons for volunteering. The implications for organizations and employees are discussed.
The Multiple Sources of Mission Drift
Authors: Jones Marshall B.
Published: May 2007

This article examines Weisbrod's contention that nonprofits should avoid unrelated business activities, primarily because of their potential for mission drift. The conclusion reached is that commercial ventures are only one among several paths to mission drift, and not the most threatening. Furthermore, the bottom line retains its potential for mission drift, even in nonprofits that have no unrelated business activities. However, if mission drift has multiple sources, then the exclusion of one relatively minor source is not an adequate remedy.
Static Aeroelastic Response of Chiral-core Airfoils
Authors: Spadoni A. , Ruzzene M.
Published: May 2007

Extensive research is being devoted to the analysis and application of cellular solids for the design of innovative structural components. The chiral geometry in particular features a unique mechanical behavior which is here exploited for the design of 2D airfoils with morphing capabilities. A coupled-physics model, comprising computational fluid dynamics and structural analyses, investigates the influence of the chiral core on the aerodynamic behavior of the airfoil. Specifically, the model predicts the static deflection of the airfoil as a result of given flow conditions. The morphing capabilities of the airfoil, here quantified as camber changes, are evaluated for various design configurations of the core.
3*3 Coupler-Based Mach-Zehnder Interferometer and Its Application in the Delamination Detection in FRP Composite
Authors: Yi Jiang  , Ying Xu  , Leung Christopher K.Y.
Published: May 2007

This article focuses on the development and application of a 3 * 3 coupler-based Mach-Zehnder interferometer. The software for signal demodulation is developed. Based on waveforms obtained at intermediate steps, plausible errors are analyzed and found to be small. The interferometer is then applied to the delamination detection in fiber-reinforced polymer (FRP) composites. Test results indicate the feasibility of detecting both the size and location of delamination by applying quasi-impulse loadings.
Feasibility of Renal Artery Stenting Before, During, and After Endovascular Aneurysm Repair With Suprarenal Fixation Endograft
Authors: Melissano Germano , Civilini Efrem , Baccellieri Domenico , Montorfano Matteo , Chiesa Roberto
Published: May 2007

Suprarenal fixation by means of proximal bare stent may help prevent endograft migration and proximal endoleak. It seems not to compromise renal perfusion and function; however, it is still unclear whether its presence is in conflict with stenting of the renal arteries to treat associated renal stenosis. We report five cases of renal artery stenting performed before, at the same time, or after endovascular treatment of abdominal aortic aneurysm with a suprarenal fixation endograft (Zenith; Cook, Biaverskov, Denmark). Suprarenal fixation endograft seems to not affect renal artery stenting regardless the timing of the procedure.
Evolution of Bacterial Arteritis Into a Mycotic Aortic Aneurysm
Authors: Phade Sachin V. , deFreitas Dorian , Powell Charles S. , Stoner Michael
Published: May 2007

Arteritis and mycotic aneurysms have been well described for more than 100 years. The authors report a case of bacterial arteritis that presented with pneumatosis of the aortic wall and that evolved over 1 week into an infected abdominal aortic aneurysm. This case documents the rapid progression from arteritis to mycotic aneurysm, highlighting the need for close radiologic follow-up and aggressive medical and surgical management.
Defective cytotoxic lymphocyte degranulation in syntaxin-11–deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients
Authors: Bryceson Yenan T. , Rudd Eva , Zheng Chengyun , Edner Josefine , Ma Daoxin , Wood Stephanie M. , Bechensteen Anne Grete , Boelens Jaap J. , Celkan Tiraje , Farah Roula A. , Hultenby Kjell , Winiarski Jacek , Roche Paul A. , Nordenskjöld Magnus , Henter Jan-Inge , Long Eric O. , Ljunggren Hans-Gustaf
Published: May 2007

Familial hemophagocytic lymphohistiocytosis (FHL) is typically an early onset, fatal disease characterized by a sepsislike illness with cytopenia, hepatosplenomegaly, and deficient lymphocyte cytotoxicity. Disease-causing mutations have been identified in genes encoding perforin (PRF1/FHL2), Munc13-4 (UNC13D/FHL3), and syntaxin-11 (STX11/FHL4). In contrast to mutations leading to loss of perforin and Munc13-4 function, it is unclear how syntaxin-11 loss-of-function mutations contribute to disease. We show here that freshly isolated, resting natural killer (NK) cells and CD8+ T cells express syntaxin-11. In infants, NK cells are the predominant perforin-containing cell type. NK cells from FHL4 patients fail to degranulate when encountering susceptible target cells. Unexpectedly, IL-2 stimulation partially restores degranulation and cytotoxicity by NK cells, which could explain the less severe disease progression observed in FHL4 patients, compared with FHL2 and FHL3 patients. Since the effector T-cell compartment is still immature in infants, our data suggest that the observed defect in NK-cell degranulation may contribute to the pathophysiology of FHL, that evaluation of NK-cell degranulation in suspected FHL patients may facilitate diagnosis, and that these new insights may offer novel therapeutic possibilities.
Identification of candidate regulatory sequences in mammalian 3' UTRs by statistical analysis of oligonucleotide distributions
Authors: Corà Davide , Di Cunto Ferdinando , Caselle Michele , Provero Paolo
Published: May 2007

Background

3' untranslated regions (3' UTRs) contain binding sites for many regulatory elements, and in particular for microRNAs (miRNAs). The importance of miRNA-mediated post-transcriptional regulation has become increasingly clear in the last few years.

Results

We propose two complementary approaches to the statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of candidate binding sites for regulatory elements. The first method is based on the identification of sets of genes characterized by evolutionarily conserved overrepresentation of an oligonucleotide. The second method is based on the identification of oligonucleotides showing statistically significant strand asymmetry in their distribution in 3' UTRs.

Conclusion

Both methods are able to identify many previously known binding sites located in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are proposed for experimental verification.
Refining intra-protein contact prediction by graph analysis
Authors: Frenkel-Morgenstern Milana , Magid Rachel , Eyal Eran , Pietrokovski Shmuel
Published: May 2007

Background

Accurate prediction of intra-protein residue contacts from sequence information will allow the prediction of protein structures. Basic predictions of such specific contacts can be further refined by jointly analyzing predicted contacts, and by adding information on the relative positions of contacts in the protein primary sequence.

Results

We introduce a method for graph analysis refinement of intra-protein contacts, termed GARP. Our previously presented intra-contact prediction method by means of pair-to-pair substitution matrix (P2PConPred) was used to test the GARP method. In our approach, the top contact predictions obtained by a basic prediction method were used as edges to create a weighted graph. The edges were scored by a mutual clustering coefficient that identifies highly connected graph regions, and by the density of edges between the sequence regions of the edge nodes. A test set of 57 proteins with known structures was used to determine contacts. GARP improves the accuracy of the P2PConPred basic prediction method in whole proteins from 12% to 18%.

Conclusion

Using a simple approach we increased the contact prediction accuracy of a basic method by 1.5 times. Our graph approach is simple to implement, can be used with various basic prediction methods, and can provide input for further downstream analyses.
Differential development of neuronal physiological responsiveness in two human neural stem cell lines
Authors: Donato Roberta , Miljan Erik A , Hines Susan J , Aouabdi Sihem , Pollock Kenneth , Patel Sara , Edwards Frances A , Sinden John D
Published: May 2007

Background

Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to neurodegenerative disease. Overexpression of the myc family transcription factors in human primary cells from developing cortex and mesencephalon has produced two stable multipotential NSC lines (ReNcell VM and CX) that can be continuously expanded in monolayer culture.

Results

In the undifferentiated state, both ReNcell VM and CX are nestin positive and have resting membrane potentials of around -60 mV but do not display any voltage-activated conductances. As initially hypothesized, using standard methods (stdD) for differentiation, both cell lines can form neurons, astrocytes and oligodendrocytes according to immunohistological characteristics. However it became clear that this was not true for electrophysiological features which designate neurons, such as the firing of action potentials. We have thus developed a new differentiation protocol, designated 'pre-aggregation differentiation' (preD) which appears to favor development of electrophysiologically functional neurons and to lead to an increase in dopaminergic neurons in the ReNcell VM line. In contrast, the protocol used had little effect on the differentiation of ReNcell CX in which dopaminergic differentiation was not observed. Moreover, after a week of differentiation with the preD protocol, 100% of ReNcell VM featured TTX-sensitive Na+-channels and fired action potentials, compared to 25% after stdD. Currents via other voltage-gated channels did not appear to depend on the differentiation protocol. ReNcell CX did not display the same electrophysiological properties as the VM line, generating voltage-dependant K+ currents but no Na+ currents or action potentials under either stdD or preD differentiation.

Conclusion

These data demonstrate that overexpression of myc in NSCs can be used to generate electrophysiologically active neurons in culture. Development of a functional neuronal phenotype may be dependent on parameters of isolation and differentiation of the cell lines, indicating that not all human NSCs are functionally equivalent.
Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase
Authors: Freistadt Marion S , Vaccaro Joseph A , Eberle Karen E
Published: May 2007

Background

Putative high mutation rates of RNA viruses are believed to mediate undesirable phenomena, such as emergence of drug resistance. However, very little is known about biochemical fidelity rates for viral RNA-dependent RNA polymerases. Using a recently developed in vitro polymerase assay for poliovirus polymerase 3Dpol [Arnold and Cameron (2000) JBC 275:5329], we measured fidelity for each possible mismatch. Polymerase fidelity, in contrast to sequence error rate, is biochemically defined as k

pol
/K

d
of {(correct plus incorrect) divided by incorrect} incorporations, such that a larger value connotes higher fidelity.

Results

To derive k

pol
/K

d
for correct base incorporation, we performed conventional pre-steady state single turnover measurements, yielding values that range from 0.62 to 9.4 μM-1 sec-1. Pre-steady state measurements for incorrect base incorporation were less straightforward: several anomalous phenomena interfered with data collection. To obtain pre-steady state kinetic data for incorrect base incorporation, three strategies were employed. (1) For some incorrect bases, a conventional approach was feasible, although care was taken to ensure that only single turnovers were being assessed. (2) Heparin or unlabeled RNA traps were used to simulate single turnover conditions. (3) Finally, for some incorrect bases, incorporation was so poor that single datapoints were used to provide kinetic estimates. Overall, we found that fidelity for poliovirus polymerase 3Dpol ranges from 1.2 × 104 to 1.0 × 106 for transition mutations and 3.2 × 105 to 4.3 × 107 for transversion mutations.

Conclusion

These values are unexpectedly high showing that high RNA virus sequence variation is not due to intrinsically low polymerase fidelity. Based on unusual enzyme behavior that we observed, we speculate that RNA mismatches either directly or indirectly cause enzyme RNA dissociation. If so, high sequence variation of RNA viruses may be due to template-switch RNA recombination and/or unknown fitness/selection phenomena. These findings may lead to a mechanistic understanding of RNA virus error catastrophe and improved anti-viral strategies.
Predicting a low cortisol response to adrenocorticotrophic hormone in the critically ill: a retrospective cohort study
Authors: de Jong Margriet FC , Beishuizen Albertus , Spijkstra Jan-Jaap , Girbes Armand RJ , Strack van Schijndel Rob JM , Twisk Jos WR , Groeneveld AB Johan
Published: May 2007

Introduction

Identification of risk factors for diminished cortisol response to adrenocorticotrophic hormone (ACTH) in the critically ill could facilitate recognition of relative adrenal insufficiency in these patients. Therefore, we studied predictors of a low cortisol response to ACTH.

Methods

A retrospective cohort study was conducted in a general intensive care unit of a university hospital over a three year period. The study included 405 critically ill patients, who underwent a 250 μg ACTH stimulation test because of prolonged hypotension or need for vasopressor/inotropic therapy. Plasma cortisol was measured before and 30 and 60 min after ACTH injection. A low adrenal response was defined as an increase in cortisol of less than 250 nmol/l or a peak cortisol level below 500 nmol/l. Various clinical variables were collected at admission and on the test day.

Results

A low ACTH response occurred in 63% of patients. Predictors, in multivariate analysis, included sepsis at admission, low platelets, low pH and bicarbonate, low albumin levels, high Sequential Organ Failure Assessment score and absence of prior cardiac surgery, and these predictors were independent of baseline cortisol and intubation with etomidate. Baseline cortisol/albumin ratios, as an index of free cortisol, were directly related and increases in cortisol/albumin were inversely related to disease severity indicators such as the Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score (Spearman r = -0.21; P < 0.0001).

Conclusion

In critically ill patients, low pH/bicarbonate and platelet count, greater severity of disease and organ failure are predictors of a low adrenocortical response to ACTH, independent of baseline cortisol values and cortisol binding capacity in blood. These findings may help to delineate relative adrenal insufficiency and suggest that adrenocortical suppression occurs as a result of metabolic acidosis and coagulation disturbances.
Excess Weight Gain during the Early Postnatal Period Is Associated with Permanent Reprogramming of Brown Adipose Tissue Adaptive Thermogenesis
Authors: Xiao Xiao Qiu , Williams Sarah M. , Grayson Bernadette E. , Glavas Maria M. , Cowley Michael A. , Smith M. Susan , Grove Kevin L.
Published: May 2007

Excess weight gain during the early postnatal period increases the risk of persistent obesity into adulthood and impacts on the subsequent risk for metabolic and cardiovascular diseases. The current study investigated the long-term effect of early excess weight gain, through reduced nursing litter size, on body weight regulation and its relation to brown adipose tissue (BAT) thermogenesis. Animals raised in a small litter (SL, three pups per litter) were compared with those raised in a normal litter size (NL, eight pups per litter). BAT from young adult NL and SL rats, maintained under either ambient or cold conditions, were used for gene expression, morphological, and functional analysis. Compared with NL, SL rats showed excess weight gain, and adult SL animals had a reduced thermogenic capacity as displayed by lower levels of uncoupling protein 1 (UCP1). When exposed to cold, BAT from SL rats was less active and demonstrated reduced responsiveness to cold. Furthermore, reduction in transcript abundance of several lipid lipases and transcriptional regulators was observed in SL rats either at ambient temperature or under cold conditions. Finally, the expression of sympathetic β3-adrenergic receptor and the response to the sympathetic receptor agonist isoproterenol were decreased in SL rats. Overall, these observations provide the first evidence that postnatal excess weight gain results in abnormalities in BAT thermogenesis and sympathetic outflow, which likely increases susceptibility to obesity in adulthood.
Musculoskeletal Tuberculosis in Bradford – A 6-Year Review
Authors: Talbot JC , Bismil Q , Saralaya D , Newton DAG , Frizzel RM , Shaw DL
Published: May 2007

INTRODUCTION

Tuberculosis (TB) remains the most common cause of death from infectious disease world-wide. In the UK, the incidence of TB has risen by 25% over the last 10 years; extrapulmonary diagnosis remains challenging and can be delayed. This study evaluates the epidemiology of musculoskeletal tuberculosis in a large multi-ethnic UK city.

PATIENTS AND METHODS

A review of prospectively recorded data of incidence, anatomical site, ethnic distribution, treatment and drug resistance of musculoskeletal tuberculosis over a 6-year period was performed.

RESULTS

From January 1999 to December 2004, there were 729 TB notifications; 61 cases (8.4%) had musculoskeletal involvement. Of the patients, 74% were immigrants from the Indian subcontinent; nearly 50% had spinal involvement; 24 patients underwent surgical intervention; 29 were subjected to either diagnostic or therapeutic radiological intervention; and resolution of symptoms was achieved in 59 out of 61 cases.

CONCLUSIONS

This study highlights the high proportion of musculoskeletal TB in immigrant patients in an area with a relatively large at-risk population, but will also serve to alert physicians, in areas with smaller at-risk populations, of the possibility of musculoskeletal TB.
A Study of the Routine Use of Venous Photoplethysmography in a One-Stop Vascular Surgery Clinic
Authors: Beraldo S , Satpathy A , Dodds SR
Published: May 2007

INTRODUCTION

The decision to offer surgical treatment for varicose veins should be based on objective evidence of venous dysfunction and not only the subjective appearance or the reported symptoms. Special tests are required to identify the sub-group of patients with functional superficial venous reflux accurately. The initial test should be simple, cheap, objective, sensitive and easy to perform by a wide range of staff in order to screen out patients without reflux. The final test should be anatomically specific to identify the appropriate surgical procedure. The aim of this study was to test the feasibility of using photoplethysmography (PPG) as the initial test as part of a one-stop vascular clinic assessment protocol.

PATIENTS AND METHODS

All patients referred to one consultant over a 68-week period were assessed using standard practice for the first 22 weeks and with an objective assessment protocol based on PPG for the subsequent 46 weeks.

RESULTS

A total of 347 out-patient appointments for patients with venous disease were booked: 239 (69%) were new referrals. Of the new patients, 59% were CEAP C2/3 and 23% were CEAP C4-6. The introduction of the objective assessment protocol was associated with a reduction in patients offered surgery from 39% to 24% overall and 51% to 28% in new patients with CEAP C2. There was a corresponding increase in the number of patients discharged back to the GP from 19% to 29% overall and 17% to 32%, respectively. The number of patients referred for duplex ultrasound fell slightly from 26% to 22%. Overall, there was a significant change in practice between the two periods (χ2 = 13.3; df = 3; P = 0.004).

CONCLUSIONS

The introduction of an objective assessment protocol based on PPG as the initial objective test reduces the number of patients offered surgery based on objective evidence of venous dysfunction.
Pre-Operative Oral Iron Supplementation Reduces Blood Transfusion in Colorectal Surgery – A Prospective, Randomised, Controlled Trial
Authors: Lidder PG , Sanders G , Whitehead E , Douie WJ , Mellor N , Lewis SJ , Hosie KB
Published: May 2007

INTRODUCTION

Allogeneic blood transfusion confers a risk to the recipient. Recent trials in colorectal surgery have shown that the most significant factors predicting blood transfusion are pre-operative haemoglobin, operative blood loss and presence of a transfusion protocol. We report a randomised, controlled trial of oral ferrous sulphate 200 mg TDS for 2 weeks' pre-operatively versus no iron therapy.

PATIENTS AND METHODS

Patients diagnosed with colorectal cancer were recruited from out-patient clinic and haematological parameters assessed. Randomisation was co-ordinated via a telephone randomisation centre.

RESULTS

Of the 49 patients recruited, 45 underwent colorectal resection. There were no differences between those patients not receiving iron (n = 23) and the iron-supplemented group (n = 22) for haemoglobin at recruitment, operative blood loss, operation duration or length of hospital stay. At admission to hospital, the iron-supplemented group had a higher haemoglobin than the non-iron treated group (mean haemoglobin concentration 13.1 g/dl [range, 9.6–17 g/dl] versus 11.8 g/dl [range, 7.8–14.7 g/dl]; P = 0.040; 95% CI 0.26–0.97) and were less likely to require operative blood transfusion (mean 0 U [range, 0–4 U] versus 2 U [range, 0–11 U] transfused; P = 0.031; 95% CI 0.13–2.59). This represented a cost reduction of 66% (47 U of blood = £4700 versus oral FeSO4 at £30 + 15 U blood at £1500). At admission, ferritin in the iron-treated group had risen significantly from 40 μg/l (range, 15–222 μg/l) to 73 μg/l (range, 27–386 μg/l; P = 0.0036; 95% CI 46.53–10.57).

CONCLUSIONS

Oral ferrous sulphate given pre-operatively in patients undergoing colorectal surgery offers a simple, inexpensive method of reducing blood transfusions.
Unplanned General Surgical Re-Admissions – How Many, Which Patients and Why?
Authors: Adeyemo Dayo , Radley Simon
Published: May 2007

INTRODUCTION

The unplanned re-admission rate is a national key performance indicator employed by the UK Department of Health. An adjusted figure, based on admission information data on the hospital electronic Patient Administration System (PAS), but adjusted to take account of case mix is compared with a calculated ‘expected’. While previous studies have investigated unplanned re-admission rates in age-, procedure- or process-specific conditions, ‘all-cause’ general surgical re-admission rate is yet to be studied. The aim of this study was to assess the accuracy of hospital unplanned re-admission data, and identify patterns or possible causes of unplanned general surgical re-admissions.

PATIENTS AND METHODS

Retrospective audit of case note records of all patients identified from the hospital electronic PAS as unplanned, general surgical re-admissions over a period of 4 consecutive months.

RESULTS

Of all 161 re-admissions in this study, 46 (29%) were unrelated to the index admission, planned or involved patient self-discharge during the index admission. Of the ‘genuine’, unplanned re-admissions, 80 (78%) followed an emergency index admission, 58 (56%) had chronic or recurrent symptoms, for which 26 (25%) were on waiting lists. Fourteen (14%) were multiple admissions of 4 patients, while 8 (8%) re-admissions required further surgery for significant postoperative complications.

CONCLUSIONS

Unplanned. general surgical re-admission rates collated from hospital PAS systems may be inaccurate. Nearly half of ‘genuine’, unplanned re-admissions involved patients with chronic and/or recurrent symptoms, which are predictable and may be preventable. Significant postoperative complications accounted for few re-admissions in this study.
AAA Benchmarking by Dr Foster: A Cause for Concern?
Authors: Pandey VA , Kerle MI , Jenkins MP , Wolfe JHN
Published: May 2007

INTRODUCTION

The publication of interpretable performance data for hospitals is an important service. In November 2002, the medical benchmarking company Dr Foster published a league table based on the results of abdominal aortic aneurysm (AAA) repair. The purpose of our study was to establish the validity of the data used in benchmarking.

PATIENTS AND METHODS

Data on elective infra-renal AAA (IRAAA) repair was obtained from three sources. Data used by Dr Foster was based on the hospital PAS system. The databases for both Dr Foster and PAS were analysed and cross-referenced to the vascular unit database maintained by a separately employed audit co-ordinator.

RESULTS

Of 395 total aortic aneurysm repairs, 223 (56%) were identified as elective IRAAA repairs on the unit database. Of these, 125 were identified on the PAS database and 115 on the Dr Foster database. The number of deaths was the same in both the unit and Dr Foster databases (n = 11) but the Dr Foster database included deaths in patients who had undergone juxtarenal (n = 1), Type III TAAA (n = 2) and Type IV TAAA (n = 4) repairs and omitted 7 deaths following IRAAA. The sensitivity and specificity for the PAS dataset was 0.51 and 0.93, respectively. For Dr Foster, the results were worse with a sensitivity and specificity of 0.41 and 0.86, respectively. The accuracy of the data was 0.6 and 0.69 for Dr Foster and PAS, respectively. Standardised mortality ratios (SMRs) were used to rank hospitals. Dr Foster's published SMR for elective AAA repair for our unit was 160. The actual SMR was 67.

CONCLUSIONS

Robust and accurate published league tables should be supported and commended but currently available data appear to be misleading and may cause unnecessary concern to patients.
Testicular Prostheses: Development and Modern Usage
Authors: Bodiwala D , Summerton DJ , Terry TR
Published: May 2007

INTRODUCTION

Testicular prostheses produced from various materials have been in use since 1941. The absence of a testicle has been shown to be a psychologically traumatic experience for males of all ages. The indications for insertion of a prosthesis include absence or following orchidectomy from a number of causes such as malignancy, torsion and orchitis. The most common substance used around the world in the manufacture of these implants is silicone; however, in the US, this material is currently banned because of theoretical health risks. This has led to the development of saline-filled prostheses as an alternative.

PATIENTS AND METHODS

A Medline search was carried out on all articles on testicular prosthesis between 1966 and 2006.

CONCLUSIONS

This review highlights the controversies regarding prosthetic materials, the complications of insertion and the potential benefits of this commonly performed procedure.
Knowledge capacity and sustainable development: The case of South African HIV vaccine development
Authors: Hanlin Rebecca
Published: May 2007

Publicprivate partnerships (PPPs) are an innovative mechanism for promoting investment in vaccine development for HIV/AIDS through the creation of economic and social incentives for collaboration. PPPs can also create important process-related, intangible value added. A case study of
the South African AIDS Vaccine Initiative conducted in mid-2005 concluded that intangible value added, occurring in the form of good collaborative effort and capacity building activities, significantly contributed to partnership working. The study also showed that often innovation and health(care)
are seen as separate areas of activity in policy development, while in reality there are linkages between these two systems, particularly when viewing PPPs from a systems of innovation perspective through the concept of absorptive capacity, which relates to the understanding of the value and
use of knowledge. A systems of innovation approach focuses on the building of knowledge capacity and knowledge flows. Policy based on this holistic and inclusive approach provides a possible means for sustainable development.
Livestock R&D in East and Southern Africa: An innovation systems perspective with special reference to the International Livestock Research Institute
Authors: Clark Norman , Smith James , Hirvonen Maija
Published: May 2007

The concept of innovation system is used increasingly in current science policy discourse as a metaphor to indicate the need for a much wider perspective on relevant decision-making procedures than has been the case in the past. This paper explores its use from the standpoint of the
behaviour of an international agricultural research institute located in Africa and focused on two vector-borne livestock diseases, trypanosomiasis and theileriosis, which form case studies for this paper. The paper argues that adopting an innovation systems perspective could open up new possibilities
for research institutes of this type with impacts on both socioeconomic development and scientific quality that are likely to be positive.
The stochastic maximum principle in optimal control of singular diffusions with non linear coefficients
Authors: Bahlali Seid , Chala Adel
Published: May 2007

We consider a stochastic control problem of a non linear system in which the variable control has two components, the first being absolutely continuous and the second singular. We assume a convex state constraint, a non convex cost criterion and we allow the absolutely continuous component of the control to enter both the drift and diffusion coefficients. The maximum principle is established by using mainly a convex perturbation on a given optimal control. This result generalizes at the same time the result obtained by Cadellinas-Haussman as well as that obtained by Bensoussan.
Evidence‐Based Practices Project for Suicide Prevention
Authors: Rodgers Philip L. , Sudak Howard S. , Silverman Morton M. , Litts David A.
Published: May 2007

Suicide continues to be a serious public health problem. In response to this problem, a myriad of suicide prevention programs have been developed and employed across the United States. Unfortunately, the effectiveness of many of these programs is unknown because they have not been evaluated using rigorous methods. The Evidence‐Based Practices Project (EBPP) for suicide prevention was created in 2002 to identify and promote evidence‐based suicide prevention programs. In this paper the process and outcomes of the initial EBPP project within the context of the broader evidence‐based movement are described, and the EBPPs creation of a best practice registry for suicide prevention is previewed.
Enhanced Unique Pattern of Hematopoietic Cell Mobilization Induced by the CXCR4 Antagonist 4F-Benzoyl-TN14003
Authors: Abraham Michal , Biyder Katia , Begin Michal , Wald Hanna , Weiss Ido D. , Galun Eithan , Nagler Arnon , Peled Amnon
Published: May 2007

An increase in the number of stem cells in blood following mobilization is required to enhance engraftment after high-dose chemotherapy and improve transplantation outcome. Therefore, an approach that improves stem cell mobilization is essential. The interaction between CXCL12 and its receptor, CXCR4, is involved in the retention of stem cells in the bone marrow. Therefore, blocking CXCR4 may result in mobilization of hematopoietic progenitor and stem cells. We have found that the CXCR4 antagonist known as 4F-benzoyl-TN14003 (T-140) can induce mobilization of hematopoietic stem cells and progenitors within a few hours post-treatment in a dose-dependent manner. Furthermore, although T-140 can also increase the number of white blood cells (WBC) in blood, including monocytes, B cells, and T cells, it had no effect on mobilizing natural killer cells. T-140 was found to efficiently synergize with granulocyte colony-stimulating factor (G-CSF) in its ability to mobilize WBC and progenitors, as well as to induce a 660-fold increase in the number of erythroblasts in peripheral blood. Comparison between the CXCR4 antagonists T-140 and AMD3100 showed that T-140 with or without G-CSF was significantly more potent in its ability to mobilize hematopoietic stem cells and progenitors into blood. These results demonstrate that different CXCR4 antagonists may have different therapeutic potentials.

Disclosure of potential conflicts of interest is found at the end of this article.
Chemotaxis and Differentiation of Human Adipose Tissue CD34+/CD31− Progenitor Cells: Role of Stromal Derived Factor-1 Released by Adipose Tissue Capillary Endothelial Cells
Authors: Sengenès Coralie , Miranville Alexandra , Maumus Marie , de Barros Sandra , Busse Rudi , Bouloumié Anne
Published: May 2007

The native CD34+/CD31− cell population present in the stroma-vascular fraction of human adipose tissue (hAT) displays progenitor cell properties since they exhibit adipocyte- and endothelial cell-like phenotypes under appropriate stimuli. To analyze the signals within hAT regulating their phenotypes, the influence of hAT-derived capillary endothelial cells (CECs) was studied on the chemotaxis and differentiation of the hAT-CD34+/CD31− cells. Conditioned medium from hAT-CECs led to a strong chemotaxis of the hAT-CD34+/CD31− cells that was inhibited with pretreatments with pertussis toxin, CXCR-4 antagonist, or neutralizing antibodies. Furthermore, hAT-CECs produced and secreted the CXCR-4 ligand, that is, the stromal derived factor-1 (SDF-1). Finally, hAT-CECs induced the differentiation of hAT-CD34+/CD31− cells toward an endothelial cell (EC) phenotype. Indeed, hAT-CECs and -CD34+/CD31− cell coculture stimulated in a two-dimensional system the expression of the EC CD31 marker by the hAT-progenitor cells and, in a three-dimensional approach, the formation of capillary-like structures via a SDF-1/CXCR-4 dependent pathway. Thus, the migration and differentiation of hAT progenitor cells are modulated by hAT-CEC-derived factors. SDF-1, which is secreted by hAT-derived CECs, and its receptor CXCR-4, expressed by hAT-derived progenitor cells, may promote chemotaxis and differentiation of hAT-derived progenitor cells and thus contribute to the formation of the vascular network during the development of hAT.

Disclosure of potential conflicts of interest is found at the end of this article.
High Histone Acetylation and Decreased Polycomb Repressive Complex 2 Member Levels Regulate Gene Specific Transcriptional Changes During Early Embryonic Stem Cell Differentiation Induced by Retinoic Acid
Authors: Lee Elliot R. , Murdoch Fern E. , Fritsch Michael K.
Published: May 2007

Histone modifications play a crucial role during embryonic stem (ES) cell differentiation. During differentiation, binding of polycomb repressive complex 2 (PRC2), which mediates trimethylation of lysine 27 on histone H3 (K27me3), is lost on developmental genes that are transcriptionally induced. We observed a global decrease in K27me3 in as little as 3 days after differentiation of mouse ES cells induced by retinoic acid (RA) treatment. The global levels of the histone K27 methyltransferase EZH2 also decreased with RA treatment. A loss of EZH2 binding and K27me3 was observed locally on PRC2 target genes induced after 3 days of RA, including Nestin. In contrast, direct RA-responsive genes that are rapidly induced, such as Hoxa1, showed a loss of EZH2 binding and K27me3 after only a few hours of RA treatment. Following differentiation induced by leukemia inhibitor factor (LIF) withdrawal without RA, Hoxa1 was not transcriptionally activated. Small interfering RNA-mediated knockdown of EZH2 resulted in loss of K27me3 during LIF withdrawal, but the Hoxa1 gene remained transcriptionally silent after loss of this repressive mark. Induction of histone hyperacetylation overrode the repressive K27me3 modification and resulted in Hoxa1 gene expression. Together, these data show that there are multiple temporal phases of derepression of PRC2 target genes during ES cell differentiation and that other epigenetic marks (specifically, increased acetylation of histones H3 and H4), in addition to derepression, are important for gene-specific transcriptional activation. This report demonstrates the temporal interplay of various epigenetic changes in regulating gene expression during early ES cell differentiation.

Disclosure of potential conflicts of interest is found at the end of this article.
Investigation of filament distribution at geotextile/geomembrane interfaces
Authors: Kim D. , Frost J. D.
Published: May 2007

This paper presents results from a study that examined the filament distributions at needle-punched nonwoven (NPNW) geotextile/HDPE geomembrane interfaces. An advanced image analysis technique was used to observe the evolution of the filament microstructure under different boundary conditions including normal force loading and unloading, as well as shear force loading to residual conditions. The different phases within the geosynthetic interface zone were detected from images captured using high-resolution optical microscopy. The changes in geotextile inner structure were statistically quantified in terms of filament nearest neighbour distance distribution and local void ratio distribution. The frequency of geotextile features within 10 μm of the interface increased by 73% as the normal stress increased from 10 to 300 kPa. The filament concentration at filament-texture interlocking points was quantified in terms of the local void ratio distribution. The study provides insight into the mechanism of geotextile microstructure evolution under different boundary conditions.
Prediction of Severe Hypoglycemia
Authors: Cox Daniel J. , Gonder-Frederick Linda , Ritterband Lee , Clarke William , Kovatchev Boris P.
Published: May 2007

OBJECTIVE—Prevention of severe hypoglycemia (SH) is premised partially on the ability to accurately anticipate its occurrence. This study prospectively tests methods for predicting SH using blood glucose meter readings.

RESEARCH DESIGN AND METHODS—One hundred adults with type 1 diabetes were followed for 6 months, and 79 insulin-using adults with type 2 diabetes were followed for 4 months. During this time, subjects’ routine self-monitored blood glucose (SMBG) readings were stored on and retrieved from memory meters, and participants were queried biweekly about occurrence of SH. Respective demographics for the two groups were age 40.7 and 50.2 years, duration of diabetes 20.0 and 12.2 years, A1C 7.6 and 8.8%, and male sex 43 and 39%, respectively.

RESULTS—Relative risk for SH, quantified by the ratio of an individual's low blood glucose index (LBGI) based on the previous 150 SMBG readings to the LBGI based on recent SMBG readings, increased significantly in the 24 h before SH episodes in individuals with type 1 and type 2 diabetes (t = 10.3, P < 0.0001, and t = 4.2, P < 0.001, respectively). A sliding algorithm detected 58% of imminent (within 24 h) SH episodes in the type 1 diabetic group and 60% of those in the type 2 diabetic group when three SMBG readings were available in the 24 h before an episode. Detection increased to 63 and 75%, respectively, if five SMBG readings were available in the 24 h before an episode.

CONCLUSIONS—SH often follows a specific blood glucose fluctuation pattern that is identifiable from SMBG. Thus, partial prediction of imminent SH is possible, providing a potential tool to trigger self-regulatory prevention of significant hypoglycemia.
Development of Diabetes in Chinese With the Metabolic Syndrome
Authors: Cheung Bernard M.Y. , Wat Nelson M.S. , Man Yu Bun , Tam Sidney , Thomas G. Neil , Leung Gabriel M. , Cheng Chun Ho , Woo Jean , Janus Edward D. , Lau Chu Pak , Lam Tai Hing , Lam Karen S.L.
Published: May 2007

OBJECTIVE—We investigated the association of the metabolic syndrome with new-onset diabetes in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort.

RESEARCH DESIGN AND METHODS—We followed up on 1,679 subjects without diabetes at baseline. Those with a previous diagnosis of diabetes or those who were receiving drug treatment were considered to be diabetic. The remaining subjects underwent a 75-g oral glucose tolerance test (OGTT). Diabetes was defined by plasma glucose ≥7.0 mmol/l with fasting and/or ≥11.1 mmol/l at 2 h.

RESULTS—The prevalences of the metabolic syndrome at baseline were 14.5 and 11.4%, respectively, according to U.S. National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. After a median of 6.4 years, there were 66 and 54 new cases of diabetes in men and women, respectively. The metabolic syndrome at baseline predicted incident diabetes. Hazard ratios (HRs) for the NCEP and IDF definitions of the syndrome were 4.1 [95% CI 2.8–6.0] and 3.5 [2.3–5.2], respectively. HRs for fasting plasma glucose (FPG) ≥6.1 or 5.6 mmol/l were 6.9 [4.1–11.5] and 4.1 [2.8–6.0], respectively. The NCEP and IDF criteria had 41.9 and 31.7% sensitivity and 87.5 and 90.2% specificity, respectively. Their positive predictive values were low, ∼20%, but their negative predictive values were ∼95%.

CONCLUSIONS—The metabolic syndrome, particularly its component, elevated FPG, predicts diabetes in Chinese. An individual without the metabolic syndrome is unlikely to develop diabetes, but one who has it should practice therapeutic lifestyle changes and have periodic FPG measurements to detect new-onset diabetes.