bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case of Mania following Deep Brain Stimulation for Obsessive Compulsive Disorder
Authors: Haq Ihtsham U. , Foote Kelly D. , Goodman Wayne K. , Ricciuti Nicola , Ward Herbert , Sudhyadhom Atchar , Jacobson Charles E. , Siddiqui Mustafa S. , Okun Michael S.
Published: August 2010

Deep brain stimulation (DBS) of the basal ganglia is an effective treatment for select movement disorders, including Parkinson’s disease, essential tremor and dystonia. Based on these successes, DBS has been explored as an experimental treatment for medication-resistant neuropsychiatric disease. During a multiyear experience employing DBS to treat patients for obsessive compulsive disorder (OCD) we encountered several unanticipated stimulation-induced psychiatric side effects. We present a case of a young woman treated for OCD with DBS of the anterior limb of the internal capsule and nucleus accumbens region, who subsequently manifested a manic episode. We aim to discuss the case details, treatment and potential neuroanatomical underpinnings of this response.
Effect of Vitamin C on Lipidperoxidation and Antioxidant Status in Tamoxifen-Treated Breast Cancer Patients
Authors: Muralikrishnan G. , Amanullah S. , Basha M.I. , Boopalan S. , Vijayakumar S. , Shakeel F.
Published: August 2010

Background: Vitamin C is a water-soluble chain-breaking antioxidant that has beneficial effects on lipid-metabolizing enzymes. In the present study, the level of thiobarbituric acid (TBA) substances and antioxidant enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase and glutathione-S-transferase were assayed. Methods: The level of TBA substances and antioxidant enzymes was determined in plasma and RBC hemolysates, respectively, in 60 postmenopausal women with breast cancer. Results: The data obtained from the study revealed that the levels of TBA and the antioxidant enzymes catalase, SOD, glutathine peroxidase and glutathine-S-transferse were significantly normalized by vitamin C treatment in the RBC hemolysate. Conclusion: The results compared vitamin C-treated breast cancer patients with normal individuals and showed that co-administration of vitamin C is more beneficial in breast cancer patients treated with tamoxifen.
Primary Synovial Sarcoma of the Lung with Intra-Cardiac Extension
Authors: Devarakonda Veena S. , Lembert Larissa , Entwistle, III John W. , Hoag Jeffrey B.
Published: August 2010

Synovial sarcomas are a distinct clinical entity occurring most often in the lower extremities. They account for 10–14% of all soft tissue sarcomas. Pulmonary synovial sarcomas are quite rare and account for less than 0.5% of all intra-thoracic neoplasms. We present the first reported case of primary pulmonary synovial sarcoma with intra cardiac extension in a 53-year-old male who presented with chronic cough. Imaging revealed a large right upper lobe mass extending through the superior pulmonary veins into the left atrium. The patient underwent a right total pneumonectomy with extraction of the left atrial mass and left atrial reconstruction. Pathology and immunohistochemistry was diagnostic of primary pulmonary synovial sarcoma positive for SYT-SSX1 gene fusion transcription.
Automatic Remote Monitoring of Implantable Cardioverter-Defibrillator Lead and Generator Performance
Authors: Varma Niraj , Michalski Justin , Epstein Andrew E. , Schweikert Robert
Published: August 2010

Background—

Monitoring performance of implantable cardioverter-defibrillator (ICD) generators and leads is important. Methods available are with in-person evaluations or by automatic remote home monitoring (HM). These were prospectively evaluated and compared in the TRUST trial. The HM technology tested performed daily self-checks and databasing with rapid event notifications for out-of-range (including asymptomatic) conditions.

Methods and Results—

Patients (n=1339) were randomly assigned after ICD implant 2:1 to HM or to conventional groups. Both groups underwent scheduled checks every 3 months and were followed for 15 months. In HM, in-person office visits were scheduled at 3 and 15 months. At 6, 9, and 12 months, HM only was used with subsequent office visits if necessary. Between these time points, ICDs triggered event notifications for system integrity problems. Patients randomly assigned to conventional follow-up were evaluated with office visits only. HM and conventional patients were similar (age, 63.3±12.8 versus 64.0±12.1 years; 72.0% versus 73.1% male; New York Heart Association II class, 55.9% versus 60.4%; left ventricular ejection fraction, 29.0±10.7% versus 28.5±9.8%; coronary artery disease, 64.8% versus 71.7%; primary prevention, 72.2% versus 73.8%; DDD devices, 57.8% versus 56.6%). Four patients crossed over from conventional to HM because of advisories. Scheduled checks were more successfully accomplished in HM (92.7% versus 89.2% in conventional,
P
<0.001). Sixty-two device-related events (53 in HM versus 9 in conventional) were observed in 46 patients (40 [4.4%] in HM versus 6 [1.39%] in conventional,
P
=0.004). Forty-seven percent were asymptomatic. HM detected generator and lead problems earlier (HM versus conventional: median, 1 versus 5 days;
P
=0.05). A total of 20 device problems (eg, lead fracture, elective replacement indicators) requiring surgical revision (0.012 per patient-year) were found, 15 in HM and 5 in the conventional groups. Other events were managed nonsurgically (eg, reprogramming, initiation of antiarrhythmics).

Conclusions—

ICD lead and generator malfunction was infrequent and often asymptomatic. Only a minority of detected events required surgical intervention. Automatic HM enhanced discovery, permitted prompt detection, and facilitated management decisions. Longitudinal parameter trending, with component function evaluated daily by remote monitoring, may enable long-term performance assessment.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00336284.
Asymmetrical demography effects on psychological climate for gender diversity: Differential effects of leader gender and work unit gender composition among Swedish doctors
Authors: Konrad Alison M , Cannings Kathleen , Goldberg Caren B
Published: August 2010

This research examined the association between gender composition of the work context and perceived reward and social outcomes for women and men. A nationally representative sample of 594 male and 430 female Swedish medical doctors responded to a survey asking them to report the gender composition of their medical unit, the gender of their immediate supervisors, and the gender of the head of their work organizations. Participants also responded to previously validated measures of perceived fairness, discrimination, organizational support, exclusion, and gender harassment. Findings indicated that: 1) women who worked in medical units with a larger percentage of men reported more gender harassment; 2) women who had a male supervisor reported less organizational support; and 3) women who worked in an organization with a male head reported more gender discrimination. For men, gender composition was unrelated to any of the outcome measures.
The problem of contemporary slavery: An international human rights challenge for social work
Authors: Androff David K.
Published: August 2010

Despite conventional wisdom that slavery has been eradicated, this analysis of the human trafficking literature reveals that this form of violent coercion and economic exploitation persists. However, there is little agreement upon definitions, estimates and responses to this problem. Differing academic and policy definitions and estimates of slavery are reviewed, in which most emphasis is placed upon sexual trafficking, while other forms such as chattel slavery, debt bondage and contract slavery are often under-recognized. There are a range of policy options for ameliorating this problem, which include social services, community-based interventions, harm reduction strategies and legal and economic responses.
Cutaneous Schwannomas in 22 Horses
Authors: Schöniger S. , Valentine B. A. , Fernandez C. J. , Summers B. A.
Published: August 2010

Schwannomas are uncommonly recognized in horses. This study describes cutaneous schwannomas in 22 horses aged 8 to 25 years: 12 male, 7 female, and 3 of unknown sex. The horses had solitary cutaneous masses: 9 on the head, 3 on the neck, and the others on the shoulder, hip, thorax, abdomen, rump, extremities, or tail. The location of 1 tumor was unknown. The dermal tumors were well demarcated and expansile. Twelve had a multinodular pattern, whereas 10 formed a single nodule. Antoni A areas were observed in all tumors, and 10 tumors contained Antoni B areas. In Antoni A areas, the densely packed spindle-shaped neoplastic cells were arranged in short fascicles with nuclear palisading. In the hypocellular Antoni B areas, neoplastic cells were separated by abundant myxomatous stroma. Tumors commonly had hyalinization of stroma and vessel walls and ancient change. Cellular vacuolation was observed in 18 tumors. In all 22 cases, neoplastic cells were immunopositive for S100 protein. Expression of laminin and glial fibrillary acidic protein was observed in all 6 tumors evaluated by immunohistochemistry for these markers. One tumor was examined ultrastructurally: Neoplastic cells had branched cytoplasmic processes and were surrounded by an external lamina. Follow-up information was available 8 months to 10 years postexcision for 9 horses, for which surgical excision of the tumor was curative. The equine cutaneous schwannomas in this study had microscopic features like those of human schwannoma and had benign clinical behavior. Correct classification of equine cutaneous schwannoma will facilitate accurate prognosis and appropriate treatment.
Evaluating the Mexican Federal District’s integrated solid waste management programme
Authors: Wismer Susan , Lopez de Alba Gomez Adriana
Published: August 2010

Generation of solid waste is a problem of great environmental significance in the Mexican Federal District. With an estimated daily generation of 12 500 tons, waste management is a priority for the district government. Integrated waste management programmes have been implemented in the Mexican Federal District in the past. They have failed. This research has examined the most recent initiative in an effort to discover the causes of failure, using a case study approach. In addition to identifying barriers to and opportunities for implementation of an effective integrated waste management system in the Federal District, this research recommends options for a newly proposed waste management system with the aim of achieving the objectives desired by the government, while aiding in the pursuit of sustainable development.
Everything all right in method comparison studies?
Authors: Alanen Erkki
Published: August 2010

Researchers and clinicians often need to know whether a new method of measurement is equivalent to an established one that is already in use. For this problem, the estimation of limits of agreement advocated by Bland and Altman is a widely used solution. However, this approach ignores two vital issues in method comparisons. First, does the appropriate re-scaling of the test method bring the methods into agreement? Second, independent of lying ‘adequately’ between the limits of agreement or not, it is important to know whether one method is equal to or better than another. This article proposes an approach and a model, where both these questions will be addressed simultaneously. In this model, the error variation of the standard method stands for ‘acceptable’ precision in measurements. Accordingly, the between-subject component of the measurements by the standard method will be used as a ‘gold standard’ against which the properties of the test method will be evaluated. Application of the model is demonstrated using the peak expiratory flow rate data of Bland and Altman.
Health Sector Reforms in Orissa
Authors: Rout Sarit Kumar
Published: August 2010

Any health sector reform aims at improving the health status of the people by affecting the organisational structure, governance system and financing variables. The health system has to perform a number of functions in order to enable more people to avail health benefits. In this context this analyses health sector reforms, approaches and challenges faced in Orissa during the reform process. The reform effort has not made substantial improvement in rural health indicators as indicated by NFHS-III. Most of the organisational and institutional changes were introduced as a part of a donor support programme and this has not been integrated into the system. Thus the health system did not improve on a sustained basis in order to achieve health sector goals. As a part of public financing, the state has not allocated resources as per the policy stance. The fiscal crisis has also resulted in reducing share of state expenditure towards health. There was also a substantially low allocation for inputs and infrastructure which affected the service delivery in rural areas. So equity and efficiency have remained two concerns in future health sector development of the state.
State Health Accounts
Authors: Annigeri Vinod B.
Published: August 2010

The attempts of developing Health Accounts are on the learning curve in most of the developing countries. Contrary to this most of the European countries and few countries in the American continent have produced health accounts. Though India did produce its Health Accounts very recently, more distance needs to be covered at the state level. Health Accounts are considered to be more useful as a policy tool for bringing in corrective measures as regards the financing of disease specific interventions. The conceptual clarity of developing such accounts are also in infancy in most of the developing countries due to the fact that the OECD model of System of Health Accounts (SHA) as well as the Producers’ Manual of Health Accounts (WHO, USAID & WORLD BANK) cannot be easily adopted and adapted in the context of developing economies. In this background the study assumes significance due to the fact that it would be an in-house and pioneering exercise to develop and understand the conceptual as well empirical issues in developing health accounts. The study would be useful for the academicians and the managers of health sector in the years to come. The lessons learnt would be useful in scaling up such experiments both at the state and national level. Health Accounts would provide broad indicators for policy makers just like the information that emanates from the National Income Accounts. Tracking down of Actors, Activities and Transactions in the health sector would help us to use the scarce resources for better governance of the health sector.
Revisiting Lysistrata: The Releaser of War
Authors: Gorman Geraldine
Published: August 2010

A nurse, educator, Quaker and mother of a son reflects on the role of conscience and imperative to action. What does it mean to heed a timeless call in a virtual society governed by an administration which promised change?
The What, How, Why, and Where of Self-Construal
Authors: Cross Susan E. , Hardin Erin E. , Gercek-Swing Berna
Published: August 2010

Since the publication of Markus and Kitayama’s pivotal article on culture and the self, the concepts of independent, relational, and interdependent self-construal have become important constructs in cultural psychology and research on the self. The authors review the history of these constructs, their measurement and manipulation, and their roles in cognition, emotion, motivation, and social behavior. They make suggestions for future research and point to problems still to be sorted out. Researchers interested in these constructs have many opportunities to make important contributions to the literature in a variety of fields, including health psychology, education, counseling, and international relations.
Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass
Authors: Gabet Yankel , Baniwal Sanjeev K. , Leclerc Nathalie , Shi Yunfan , Kohn-Gabet Alice E. , Cogan Jon , Dixon Alexis , Bachar Marilyn , Guo Lixin , Turman Jack E. , Frenkel Baruch
Published: August 2010

Krox20/EGR2, one of the 4 early growth response genes, is a highly conserved transcription factor implicated in hindbrain development, peripheral nerve myelination, tumor suppression, and monocyte/macrophage cell fate determination. Here, we established a novel role for Krox20 in postnatal skeletal metabolism. Microcomputed tomographic analysis of 4- and 8-week-old mice revealed a low bone mass phenotype (LBM) in both the distal femur and the vertebra of Krox20+/− mice. This was attributable to accelerated bone resorption as demonstrated in vivo by increased osteoclast number and serum C-terminal telopeptides, a marker for collagen degradation. Krox20 haploinsufficiency did not reduce bone formation in vivo, nor did it compromise osteoblast differentiation in vitro. In contrast, growth and differentiation were significantly stimulated in preosteoclast cultures derived from Krox20+/− splenocytes, suggesting that the LBM is attributable to Krox20 haploinsufficiency in the monocytic lineage. Furthermore, Krox20 silencing in preosteoclasts increased cFms expression and response to macrophage colony-stimulating factor, leading to a cell-autonomous stimulation of cell-cycle progression. Our data indicate that the antimitogenic role of Krox20 in preosteoclasts is the predominant mechanism underlying the LBM phenotype of Krox20-deficient mice. Stimulation of Krox20 expression in preosteoclasts may present a viable therapeutic strategy for high-turnover osteoporosis.
Simian immunodeficiency virus selectively infects proliferating CD4+ T cells in neonatal rhesus macaques
Authors: Wang Xiaolei , Xu Huanbin , Pahar Bapi , Alvarez Xavier , Green Linda C. , Dufour Jason , Moroney-Rasmussen Terri , Lackner Andrew A. , Veazey Ronald S.
Published: August 2010

Infants infected with HIV have a more severe course of disease and persistently higher viral loads than HIV-infected adults. However, the underlying pathogenesis of this exacerbation remains obscure. Here we compared the rate of CD4+ and CD8+ T-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (SIV)–infected neonates. The results demonstrate infant primates have much greater rates of CD4+ T-cell proliferation than adult macaques, and that these proliferating, recently “activated” CD4+ T cells are infected in intestinal and other lymphoid tissues of neonates, resulting in selective depletion of proliferating CD4+ T cells in acute infection. This depletion is accompanied by a marked increase in CD8+ T-cell activation and production, particularly in the intestinal tract. The data indicate intestinal CD4+ T cells of infant primates have a markedly accelerated rate of proliferation and maturation resulting in more rapid and sustained production of optimal target cells (activated memory CD4+ T cells), which may explain the sustained “peak” viremia characteristic of pediatric HIV infection. Eventual failure of CD4+ T-cell turnover in intestinal tissues may indicate a poorer prognosis for HIV-infected infants.
Coverage statistics for sequence census methods
Authors: Evans Steven N , Hower Valerie , Pachter Lior
Published: August 2010

Background

We study the statistical properties of fragment coverage in genome sequencing experiments. In an extension of the classic Lander-Waterman model, we consider the effect of the length distribution of fragments. We also introduce a coding of theshapeof the coverage depth function as a tree and explain how this can be used to detect regions with anomalous coverage. This modeling perspective is especially germane to current high-throughput sequencing experiments, where both sample preparation protocols and sequencing technology particulars can affect fragment length distributions.

Results

Under the mild assumptions that fragment start sites are Poisson distributed and successive fragment lengths are independent and identically distributed, we observe that, regardless of fragment length distribution, the fragments produced in a sequencing experiment can be viewed as resulting from a two-dimensional spatial Poisson process. We then study the successive jumps of the coverage function, and show that they can be encoded as a random tree that is approximately a Galton-Watson tree with generation-dependent geometric offspring distributions whose parameters can be computed.

Conclusions

We extend standard analyses of shotgun sequencing that focus on coverage statistics at individual sites, and provide a null model for detecting deviations from random coverage in high-throughput sequence census based experiments. Our approach leads to explicit determinations of the null distributions of certain test statistics, while for others it greatly simplifies the approximation of their null distributions by simulation. Our focus on fragments also leads to a new approach to visualizing sequencing data that is of independent interest.
Asymmetric localization of Arabidopsis SYP124 syntaxin at the pollen tube apical and sub-apical zones is involved in tip growth
Authors: Silva Pedro Ângelo , Ul-Rehman Reiaz , Rato Cláudia , Di Sansebastiano Gian-Pietro , Malhó Rui
Published: August 2010

Background

The continuous polarized vesicle secretion in pollen tubes is essential for tip growth but the location of endo- and exocytic sub-domains remains however controversial. In this report we aimed to show that Arabidopsis thaliana syntaxins are involved in this process and contribute to spatially define exocytosis and membrane recycling.

Results

Using GFP-fusion constructs, we imaged the distribution of pollen-specific (AtSYP124) and non-pollen syntaxins (AtSYP121 and AtSYP122) in transiently transformed Nicotiana tabacum pollen tubes. All three proteins associate with the plasma membrane and with apical vesicles indicating a conserved action mechanism for all SYPs. However, the GFP tagged SYP124 showed a specific distribution with a higher labelling at the plasma membrane flanks, 10-25 μm behind the apex. This distribution is affected by Ca2+ fluxes as revealed by treatment with Gd3+ (an inhibitor of extracellular Ca2+ influx) and TMB-8 (an inhibitor of intracellular Ca2+ release). Both inhibitors decreased growth rate but the distribution of SYP124 at the plasma membrane was more strongly affected by Gd3+. Competition with a related dominant negative mutant affected the specific distribution of SYP124 but not tip growth. In contrast, co-expression of the phosphatidylinositol-4-monophosphate 5-kinase 4 (PIP5K4) or of the small GTPase Rab11 perturbed polarity and the normal distribution of GFP-SYP but did not inhibit the accumulation in vesicles or at the plasma membrane.

Conclusions

The results presented suggest that in normal growing pollen tubes, a net exocytic flow occurs in the flanks of the tube apex mediated by SYP124. The specific distribution of SYP124 at the plasma membrane is affected by changes in Ca2+ levels in agreement with the importance of this ion for exocytosis. Apical growth and the specific localization of SYP124 were affected by regulators of membrane secretion (Ca2+, PIP5K4 and Rab11) but competition with a dominant negative mutant affected only SYP distribution. These data thus suggest that syntaxins alone do not provide the level of specificity that is required for apical growth and that additional signalling and functional mechanisms are required.
In vivo expression of innate immunity markers in patients with mycobacterium tuberculosis infection
Authors: Constantoulakis Pantelis , Filiou Eftihia , Rovina Nikoletta , Chras George , Hamhougia Aggeliki , Karabela Simona , Sotiriou Adamandia , Roussos Charis , Poulakis Nikolaos
Published: August 2010

Background

Toll-like receptors (TLRs), Coronin-1 and Sp110 are essential factors for the containment of Mycobacterium tuberculosis infection. The purpose of this study was to investigate the in vivo expression of these molecules at different stages of the infection and uncover possible relationships between these markers and the state of the disease.

Methods

Twenty-two patients with active tuberculosis, 15 close contacts of subjects with latent disease, 17 close contacts of subjects negative for mycobacterium antigens and 10 healthy, unrelated to patients, subjects were studied. Quantitative mRNA expression of Coronin-1, Sp110, TLRs-1,-2,-4 and -6 was analysed in total blood cells vs an endogenous house-keeping gene.

Results

The mRNA expression of Coronin-1, Sp110 and TLR-2 was significantly higher in patients with active tuberculosis and subjects with latent disease compared to the uninfected ones. Positive linear correlation for the expression of those factors was only found in the infected populations.

Conclusions

Our results suggest that the up-regulation of Coronin-1 and Sp110, through a pathway that also includes TLR-2 up-regulation may be involved in the process of tuberculous infection in humans. However, further studies are needed, in order to elucidate whether the selective upregulation of these factors in the infected patients could serve as a specific molecular marker of tuberculosis.
Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor
Authors: Hwang Jun-Eul , Yoon Ju-Young , Bae Woo-Kyun , Shim Hyun-Jeong , Cho Sang-Hee , Chung Ik-Joo
Published: August 2010

Background

Imatinib mesylate has been used for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST). The current recommended dose of imatinib is 400 mg/day that is increased to 800 mg/day in cases with disease progression. However, imatinib can be associated with diverse adverse events, which has limited its use. We report a case of severe adverse skin reactions with neutropenic fever during imatinib treatment in a patient with GIST.

Case presentation

A 71-year-old man was admitted with a one month history of epigastric pain and a palpable mass in the right upper quadrant. An abdominal CT scan revealed a 20 × 19 cm intraabdominal mass with tumor invasion into the peritoneum. Needle biopsy was performed and the results showed spindle shaped tumor cells that were positive for c-KIT. The patient was diagnosed with unresectable GIST. Imatinib 400 mg/day was started. The patient tolerated the first eight weeks of treatment. However, about three months later, the patient developed a grade 4 febrile neutropenia and a grade 3 exfoliative skin rash. The patient recovered from this serious adverse events after discontinuation of imatinib with supportive care. However, the skin lesions recurred whenever the patient received imatinib over 100 mg/day. Therefore, imatinib 100 mg/day was maintained. Despite the low dose imatinib, follow up CT showed a marked partial response without grade 3 or 4 toxicities.

Conclusion

The recommended dose of imatinib for the treatment of GIST is 400 mg/day but patients at risk for adverse drug reaction may benefit from lower doses. Individualized treatment is needed for such patients, and we may also try sunitinib as a alternative drug.
Asthma in changing environments - chances and challenges of international research collaborations between South America and Europe - study protocol and description of the data acquisition of a case-control-study
Authors: Boneberger Anja , Radon Katja , Baer Jennifer , Kausel Leonie , Kabesch Michael , Haider Daniel , Schierl Rudolf , von Kries Rüdiger , Calvo Mario
Published: August 2010

Background

Asthma in children is an emerging public health problem in South America. So far, research in this part of the world is limited. This paper presents the methodology and description of the data acquisition of an asthma case-control study conducted in the Central South of Chile.

Methods/Design

A hospital-based case-control study about asthma (188 cases, 294 controls) in children (6-15 years) was carried out in Valdivia, Chile between November 2008 and December 2009. Data on asthma risk factors were collected by computer-assisted personal interview using validated questions from e.g. ISAAC phase II. Data on household dust exposure (endotoxin, allergen analyses), skin prick tests to most common allergens, stool examinations for parasitic infection, and blood samples (total IgE, genetics) were collected. Additionally, 492 randomly chosen blood donors were recruited in order to assess allele frequencies in the population of Valdivia.

Discussion

Overall 1,173 participants were contacted. Response was 82% among cases and 65% among controls. Atopic sensitization was high (78% among cases, 47% among controls). Cases had a statistically significantly (p < .0001) increased self-reported 12-month prevalence of symptoms of rhinitis (82% vs. 51%) and wheeze (68% vs. 16%). The study is well placed to address current hypotheses about asthma and its correlates in the South American context. Results of this study might help develop novel, innovative and individualized prevention strategies in countries in transition with respect to the South American context.
Inhibition of allogeneic inflammatory responses by the Ribonucleotide Reductase Inhibitors, Didox and Trimidox
Authors: Inayat Mohammed S , El-Amouri Ismail S , Bani-Ahmad Mohammad , Elford Howard L , Gallicchio Vincent S , Oakley Oliver R
Published: August 2010

Background

Graft-versus-host disease is the single most important obstacle facing successful allogeneic stem cell transplantation (SCT). Even with current immunosuppressive therapies, morbidity and mortality rates are high. Current therapies including cyclosporine A (CyA) and related compounds target IL-2 signaling. However, although these compounds offer great benefit, they are also associated with multiple toxicities. Therefore, new compounds with a greater efficacy and reduced toxicity are needed to enable us to overcome this hurdle.

Methods

The allogeneic mixed lymphocyte reaction (MLR) is a uniqueex vivomethod to study a drug's action on the initial events resulting in T-cell activation and proliferation, synonymous to the initial stages of tissue and organ destruction by T-cell responses in organ rejection and Graft-versus-host disease. Using this approach, we examined the effectiveness of two ribonucleotide reductase inhibitors (RRI), Didox and Trimidox, to inhibit T-cell activation and proliferation.

Results

The compounds caused a marked reduction in the proliferative responses of T-cells, which is also accompanied by decreased secretion of cytokines IL-6, IFN-γ, TNF-α, IL-2, IL-13, IL-10 and IL-4.

Conclusions

In conclusion, these data provide critical information to justify further investigation into the potential use of these compounds post allogeneic bone marrow transplantation to alleviate graft-versus-host disease thereby achieving better outcomes.
Strengthening the emergency healthcare system for mothers and children in The Gambia
Authors: Cole-Ceesay Ramou , Cherian Meena , Sonko Alieu , Shivute Nestor , Cham Mamady , Davis Michael , Fatty Famara , Wieteska Susan , Baro Momodou , Watson Diane , Phillips Barbara , MacDonald Rhona , Hayden Brigid , Southall David
Published: August 2010

A system to improve the management of emergencies during pregnancy, childbirth, infancy and childhood in a region of The Gambia (Brikama) with a population of approximately 250,000 has been developed.

This was accomplished through formal partnership between the Gambian Ministry of Health, the World Health Organisation, Maternal Childhealth Advocacy International and the Advanced Life Support Group.

Since October 2006, the hospital in Brikama has been renovated and equipped and more efficiently provided with emergency medicines. An emergency ambulance service now links the community with the hospital through a mobile telephone system. Health professionals from community to hospital have been trained in obstetric, neonatal and paediatric emergency management using skills' based education. The programme was evaluated in log books detailing individual resuscitations and by external assessment.

The hospital now has constant water and electricity, a functioning operating theatre and emergency room; the maternity unit and children's wards have better emergency equipment and there is a more reliable supply of oxygen and emergency drugs, including misoprostol (for treating post partum haemorrhage) and magnesium sulphate (for severe pre-eclampsia). There is also a blood transfusion service.

Countrywide, 217 doctors, nurses, and midwives have undergone accredited training in the provision of emergency maternal, newborn and child care, including for major trauma. 33 have received additional education through Generic Instructor Courses and 15 have reached full instructor status. 83 Traditional Birth Attendants and 48 Village Health Workers have been trained in the recognition and initial management of emergencies, including resuscitation of the newborn. Eleven and ten nurses underwent training in peri-operative nursing and anaesthetics respectively, to address the acute shortage required for emergency Caesarean section.

Between May 2007 and March 2010, 109 patients, mostly pregnant mothers, were stabilised and transported to hospital by the new emergency ambulance service.

293 resuscitation attempts were documented in personal logbooks.

A sustainable system for better managing emergencies has been established and is helping to negate the main obstacle impeding progress: the country's lack of available trained medical and nursing staff. However, insufficient attention was paid to improving staff morale and accommodation representing significant failings of the programme.
Condensation oscillations in the peptidization of phenylglycine
Authors: Sajewicz Mieczysław , Gontarska Monika , Kronenbach Dorota , Leda Marcin , Kowalska Teresa , Epstein Irving R
Published: August 2010

In earlier studies, we showed that certain low-molecular-weight carboxylic acids (profens, amino acids, hydroxy acids) can undergo spontaneous in vitro chiral conversion accompanied by condensation to from oligomers, and we proposed two simple models to describe these processes. Here, we present the results of investigations using non-chiral high-performance liquid chromatography with diode array detector (HPLC-DAD) and mass spectrometry (MS) on the dynamics of peptidization of S-, R-, and rac-phenylglycine dissolved in 70% aqueous ethanol and stored for times up to one year. The experimental results demonstrate that peptidization of phenylglycine can occur in an oscillatory fashion. We also describe, and carry out simulations with, three models that capture key aspects of the oscillatory condensation and chiral conversion processes.
Accelerating migration deconvolution using a nonmonotone gradient method
Authors: Wang Yanfei , Yang Changchun
Published: August 2010

New solution methods were considered for migration deconvolution in seismic imaging problems. It is well known that direct migration methods, using the adjoint operator [Formula: see text], yield a lower-resolution or blurred image, and that the linearized inversion of seismic data for the reflectivity model usually requires solving a (regularized) least-squares migration problem. We observed that the (regularized) least-squares method is computationally expensive, which becomes a severe obstacle for practical applications. Iterative gradient-descent methods were studied and an efficient method for migration deconvolution was developed. The problem was formulated by incorporating regularizing constraints, and then a nonmonotone gradient-descent method was applied to accelerate the convergence. To test the potential of the application of the developed method, synthetic two-dimensional and three-dimensional seismic-migration-deconvolution simulations were performed. Numerical performance indicates that this method is promising for practical seismic migration imaging.
Unsplit complex frequency-shifted PML implementation using auxiliary differential equations for seismic wave modeling
Authors: Zhang Wei , Shen Yang
Published: August 2010

The complex-frequency-shifted perfectly matched layer (CFS-PML) technique can efficiently absorb near-grazing incident waves. In seismic wave modeling, CFS-PML has been implemented by the first-order-accuracy convolutional PML technique or second-order-accuracy recursive convolution PML technique. Both use different algorithms than the numerical scheme for the interior domain to update auxiliary memory variables in the PML and thus cannot be used directly with higher-order time-marching schemes. We work with an unsplit-field CFS-PML implementation using auxiliary differential equations (ADEs) to update the auxiliary memory variables. This ADE CFS-PML results in complete first-order differential equations. Thus, the numerical scheme for the interior domain can be used to solve ADE CFS-PML equations. We have implemented ADE CFS-PML in the finite-difference time-domain method and in anonstaggered-grid finite-difference method with the fourth-order Runge-Kutta scheme, demonstrating its straightforward implementation in different numerical time-marching schemes. We have also theoretically analyzed the role of the scalingfactor of CFS-PML; it transforms the PML to a transversely isotropic material, reducing the effective wave speed normal to the PML layer and bending the wavefront toward the normal direction of the PML layer. Our numerical tests indicate that the optimal value reduces the points per dominant wavelength at the outermost boundary to three, about half the value required by the numerical scheme. We also have found that the PML equations should be derived taking the free-surface boundary condition into account in finite-difference methods. Otherwise, the free surface in the PML layer causes instability or ineffective absorption of surface waves. Tests show that we can use a narrow-slice mesh with ADE CFS-PML to simulate full wave propagation efficiently in models with complex structure.
Automatic first-breaks picking: New strategies and algorithms
Authors: Sabbione Juan I. , Velis Danilo
Published: August 2010

We have developed three methods for the automatic picking of first breaks that can be used for marine, dynamite, or vibroseis shot records: a modified Coppens’s method, an entropy-based method, and a variogram fractal-dimension method. The techniques are based on the fact that the transition between noise and noise plus signal can be automatically identified by detecting rapid changes in a certain attribute (energy ratio, entropy, or fractal dimension), which we calculate within moving windows along the seismic trace. The application of appropriate edge-preserving smoothing operators to enhance these transitions allowed us to develop an automated strategy that can be used to easily signal the precise location of the first-arrival onset. Furthermore, we propose a mispick-correcting technique to exploit the benefits of the data present in the entire shot record, which allows us to adjust the trace-by-trace picks and to discard picks associated with bad or dead traces. As a result, the consistency of the first-break picks is significantly improved. The methods are robust under noisy conditions, computationally efficient, and easy to apply. Results using dynamite and vibroseis field data show that accurate and consistent picks can be obtained in an automated manner even under the presence of correlated noise, bad traces, pulse changes, and indistinct first breaks.
Levels of Neonatal Thyroid Hormone in Preterm Infants and Neurodevelopmental Outcome at 5½ Years: Millennium Cohort Study
Authors: Delahunty Caroline , Falconer Shona , Hume Robert , Jackson Lesley , Midgley Paula , Mirfield Marie , Ogston Simon , Perra Oliver , Simpson Judith , Watson Jennifer , Willatts Peter , Williams Fiona ,   the Scottish Preterm Thyroid Group
Published: August 2010

Context: Transient hypothyroxinemia is the commonest thyroid dysfunction of premature infants, and recent studies have found adverse associations with neurodevelopment. The validity of these associations is unclear because the studies adjusted for a differing range of factors likely to influence neurodevelopment.

Objective: The aim was to describe the association of transient hypothyroxinemia with neurodevelopment at 5.5 yr corrected age.

Design: We conducted a follow-up study of a cohort of infants born in Scotland from 1999 to 2001 ≤34 wk gestation.

Main Outcome Measures: We measured scores on the McCarthy scale adjusted for 26 influences of neurodevelopment including parental intellect, home environment, breast or formula fed, growth retardation, and use of postnatal drugs.

Results: A total of 442 infants ≤34 wk gestation who had serum T4 measurements on postnatal d 7, 14, or 28 and 100 term infants who had serum T4 measured in cord blood were followed up at 5.5 yr. Infants with hypothyroxinemia (T4 level ≤ 10th percentile on d 7, 14, or 28 corrected for gestational age) scored significantly lower than euthyroid infants (T4 level greater than the 10th percentile and less than the 90th percentile on all days) on all McCarthy scales, except the quantitative. After adjustment for confounders of neurodevelopment, hypothyroxinemic infants scored significantly lower than euthyroid infants on the general cognitive and verbal scales.

Conclusions: Our findings do not support the view that the hypothyroxinemic state, in the context of this analysis, is harmless in preterm infants. Many factors contribute both to the etiology of hypothyroxinemia and neurodevelopment; strategies for correction of hypothyroxinemia should acknowledge its complex etiology and not rely solely on one approach.
A Confidence Interval Procedure for Expected Shortfall Risk Measurement via Two-Level Simulation
Authors: Lan Hai , Nelson Barry L. , Staum Jeremy
Published: August 2010

We develop and evaluate a two-level simulation procedure that produces a confidence interval for expected shortfall. The outer level of simulation generates financial scenarios, whereas the inner level estimates expected loss conditional on each scenario. Our procedure uses the statistical theory of empirical likelihood to construct a confidence interval. It also uses tools from the ranking-and-selection literature to make the simulation efficient.
Malignancy Risk for Fine-Needle Aspiration of Thyroid Lesions According to The Bethesda System for Reporting Thyroid Cytopathology
Authors: Jo Vickie Y. , Stelow Edward B. , Dustin Simone M. , Hanley Krisztina Z.
Published: August 2010

Fine-needle aspiration (FNA) is an important test for triaging patients with thyroid nodules. The 2007 National Cancer Institute Thyroid Fine-Needle Aspiration State-of-the-Science Conference helped instigate the recent publication of The Bethesda System for Reporting Thyroid Cytopathology. We reviewed 3,080 thyroid FNA samples and recorded interpretations according to the proposed standardized 6-tier nomenclature, and pursued follow-up cytology and histology. Of the 3,080 FNAs, 18.6% were nondiagnostic, 59.0% were benign, 3.4% were atypical follicular lesion of undetermined significance (AFLUS), 9.7% were “suspicious” for follicular neoplasm (SFN), 2.3% were suspicious for malignancy (SM), and 7.0% were malignant. Of 574 cases originally interpreted as nondiagnostic, 47.9% remained nondiagnostic. In 892 cases, there was follow-up histology. Rates of malignancy were as follows: nondiagnostic, 8.9%; benign, 1.1%; AFLUS, 17% (9/53); SFN, 25.4%; SM, 70% (39/56), and malignant, 98.1%. Thus, classification of thyroid FNA samples at the University of Virginia Health System, Charlottesville, according to The Bethesda System yields similar results for risk of malignancy as reported by others. Universal application of the new standardized nomenclature may improve interlaboratory agreement and lead to more consistent management approaches.
The World Health Organization African Region Laboratory Accreditation Process
Authors: Gershy-Damet Guy-Michel , Rotz Philip , Cross David , Belabbes El Hadj , Cham Fatim , Ndihokubwayo Jean-Bosco , Fine Glen , Zeh Clement , Njukeng Patrick A. , Mboup Souleymane , Sesse Daniel E. , Messele Tsehaynesh , Birx Deborah L. , Nkengasong John N.
Published: August 2010

Few developing countries have established laboratory quality standards that are affordable and easy to implement and monitor. To address this challenge, the World Health Organization Regional Office for Africa (WHO AFRO) established a stepwise approach, using a 0- to 5-star scale, to the recognition of evolving fulfillment of the ISO 15189 standard rather than pass-fail grading. Laboratories that fail to achieve an assessment score of at least 55% will not be awarded a star ranking. Laboratories that achieve 95% or more will receive a 5-star rating.

This stepwise approach acknowledges to laboratories where they stand, supports them with a series of evaluations to use to demonstrate improvement, and recognizes and rewards their progress. WHO AFRO’s accreditation process is not intended to replace established ISO 15189 accreditation schemes, but rather to provide an interim pathway to the realization of international laboratory standards. Laboratories that demonstrate outstanding performance in the WHO-AFRO process will be strongly encouraged to enroll in an established ISO 15189 accreditation scheme. We believe that the WHO-AFRO approach for laboratory accreditation is affordable, sustainable, effective, and scalable.
Field Experience in Implementing ISO 15189 in Kisumu, Kenya
Authors: Zeh Clement E. , Inzaule Seth C. , Magero Valentine O. , Thomas Timothy K. , Laserson Kayla F. , Hart Clyde E. , Nkengasong John N.
Published: August 2010

Quality medical laboratory services are an integral part of routine health care, medical research, and public health systems. Despite this vital role, quality laboratory services in Africa are scarce. The crucial need for expanding quality laboratory services throughout sub-Saharan Africa is especially critical because of the region’s burden of disease. Fortunately, several plans from supporting international partners are underway to help strengthen laboratory infrastructure in this region. A key component of these initiatives is the enforcement of quality assurance services through accreditation by international standards such as the International Organization for Standardization (ISO) 15189. However, acquisition and maintenance of these standards are a significant challenge, especially in resource-limited settings. The most common limiting factors can include funding, government support, equipment, training opportunities, and poor procurement infrastructure. In this article, we discuss the challenges and benefits accrued in pursuing and sustaining ISO 15189 accreditation for the Kenya Medical Research Institute/Centre for Disease Control HIV-Research Laboratory in Kisumu, Kenya.