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Search Results: 1 - 10 of 201808 matches for " Nicholas D. Walter "
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A Transcriptional Signature for Active TB: Have We Found the Needle in the Haystack?
Adithya Cattamanchi ,Nicholas D. Walter,John Z. Metcalfe,J. Lucian Davis
PLOS Medicine , 2013, DOI: 10.1371/journal.pmed.1001539
Population-Level Impact of Same-Day Microscopy and Xpert MTB/RIF for Tuberculosis Diagnosis in Africa
David W. Dowdy, J. Lucian Davis, Saskia den Boon, Nicholas D. Walter, Achilles Katamba, Adithya Cattamanchi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070485
Abstract: Objective To compare the population-level impact of two World Health Organization-endorsed strategies for improving the diagnosis of tuberculosis (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA). Methods We created a compartmental transmission model of TB in a representative African community, fit to the regional incidence and mortality of TB and HIV. We compared the population-level reduction in TB burden over ten years achievable with implementation over two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of both approaches. Findings Same-day microscopy averted an estimated 11.0% of TB incidence over ten years (95% uncertainty range, UR: 3.3%–22.5%), and prevented 11.8% of all TB deaths (95% UR: 7.7%–27.1%). Scaling up Xpert MTB/RIF to all centralized laboratories to achieve 75% population coverage had similar impact on incidence (9.3% reduction, 95% UR: 1.9%–21.5%) and greater effect on mortality (23.8% reduction, 95% UR: 8.6%–33.4%). Combining the two strategies (i.e., same-day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7% reduction in incidence (95% UR: 5.6%–39.2%) and 33.1% reduction in TB mortality (95% UR: 18.1%–50.2%). By the end of year ten, combining same-day microscopy and Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current standard of care. Conclusion Scaling up novel diagnostic tests for TB and optimizing existing ones are complementary strategies that, when combined, may have substantial impact on TB epidemics in Africa.
CyberKnife? radiosurgery in the treatment of complex skull base tumors: analysis of treatment planning parameters
Sean P Collins, Nicholas D Coppa, Ying Zhang, Brian T Collins, Donald A McRae, Walter C Jean
Radiation Oncology , 2006, DOI: 10.1186/1748-717x-1-46
Abstract: At Georgetown University Hospital from March 2002 through May 2005, the CyberKnife? was used to treat 80 patients with 82 base of skull lesions. Tumors were classified as simple or complex based on their proximity to adjacent critical structures. All planning and treatments were performed by the same radiosurgery team with the goal of minimizing dosage to adjacent critical structures and maximizing target coverage. Treatments were fractionated to allow for safer delivery of radiation to both large tumors and tumors in close proximity to critical structures.The CyberKnife? treatment planning system was capable of generating highly conformal and homogeneous plans for complex skull base tumors. The treatment planning parameters did not significantly vary between spherical and non-spherical target volumes. The treatment parameters obtained from the plans of the complex base of skull group, including new conformity index, homogeneity index and percentage tumor coverage, were not significantly different from those of the simple group.Our data indicate that CyberKnife? treatment plans with excellent homogeneity, conformity and percent target coverage can be obtained for complex skull base tumors. Longer follow-up will be required to determine the safety and efficacy of fractionated treatment of these lesions with this radiosurgical system.Lesions of the base of skull are typically slow growing, but potentially morbid tumors [1]. They rarely metastasize making local control the primary determinant of long-term survival [2]. Although surgical resection may still be the treatment "gold-standard" [3,4], radiosurgery is an appropriate treatment option for many patients [5]. However, single-fraction radiosurgical treatment may be difficult because of the potentially large size and irregular shapes of these tumors. Their proximity to critical structures also leads to a risk of radiation-induced, long-term, neurological complication [6].The CyberKnife? is a newly FDA approved radi
Treatment of malignant tumors of the skull base with multi-session radiosurgery
Nicholas D Coppa, Daniel MS Raper, Ying Zhang, Brian T Collins, K William Harter, Gregory J Gagnon, Sean P Collins, Walter C Jean
Journal of Hematology & Oncology , 2009, DOI: 10.1186/1756-8722-2-16
Abstract: Clinical and radiographic data for 37 patients treated with image-guided, multi-session radiosurgery between January 2002 and December 2007 were reviewed retrospectively. Lesions were classified according to involvement with the bones of the base of the skull and proximity to the cranial nerves.Our cohort consisted of 37 patients. Six patients with follow-up periods less than four weeks were eliminated from statistical consideration, thus leaving the data from 31 patients to be analyzed. The median follow-up was 37 weeks. Ten patients (32%) were alive at the end of the follow-up period. At last follow-up, or the time of death from systemic disease, tumor regression or stable local disease was observed in 23 lesions, representing an overall tumor control rate of 74%. For the remainder of lesions, the median time to progression was 24 weeks. The median progression-free survival was 230 weeks. The median overall survival was 39 weeks. In the absence of tumor progression, there were no cranial nerve, brainstem or vascular complications referable specifically to CyberKnife? radiosurgery.Our experience suggests that multi-session radiosurgery for the treatment of malignant skull base tumors is comparable to other radiosurgical techniques in progression-free survival, local tumor control, and adverse effects.A variety of malignant tumors can involve the skull base. These tumors may originate from various tissues of the skull base, or invade into the region as extensions of head and neck cancers [1,2]. The skull base is also a common site of metastasis from distant tumors [3,4]. Patients with skull base malignancies suffer greatly [5]. Common clinical presentations include pain and cranial nerve deficits, such as visual disturbances, facial paresis and swallowing difficulties [3]. Treatment of these tumors presents formidable challenges to the clinician. In addition to neurological factors, such as the close proximity of critical neurovascular structures, oncological factor
Why first-level health workers fail to follow guidelines for managing severe disease in children in the Coast Region, the United Republic of Tanzania
Walter,Nicholas D; Lyimo,Thomas; Skarbinski,Jacek; Metta,Emmy; Kahigwa,Elizeus; Flannery,Brendan; Dowell,Scott F; Abdulla,Salim; Kachur,S Patrick;
Bulletin of the World Health Organization , 2009, DOI: 10.1590/S0042-96862009000200011
Abstract: objective: to determine why health workers fail to follow integrated management of childhood illness (imci) guidelines for severely ill children at first-level outpatient health facilities in rural areas of the united republic of tanzania. methods: retrospective and prospective case reviews of severely ill children aged < 5 years were conducted at health facilities in four districts. we ascertained treatment and examined the characteristics associated with referral, conducted follow-up interviews with parents of severely ill children, and gave health workers questionnaires and interviews. findings: in total, 502 cases were reviewed at 62 facilities. treatment with antimalarials and antibiotics was consistent with the diagnosis given by health workers. however, of 240 children classified as having "very severe febrile disease", none received all imci-recommended therapies, and only 25% of severely ill children were referred. lethargy and anaemia diagnoses were independently associated with referral. most (91%) health workers indicated that certain severe conditions can be managed without referral. conclusion: the health workers surveyed rarely adhered to imci treatment and referral guidelines for children with severe illness. they administered therapy based on narrow diagnoses rather than imci classifications, disagreed with referral guidelines and often considered referral unnecessary. to improve implementation of imci, attention should focus on the reasons for health worker non-adherence.
Increased Lysis of Stem Cells but Not Their Differentiated Cells by Natural Killer Cells; De-Differentiation or Reprogramming Activates NK Cells
Han-Ching Tseng,Aida Arasteh,Avina Paranjpe,Antonia Teruel,Wendy Yang,Armin Behel,Jackelyn A. Alva,Gina Walter,Christian Head,Tomo-o Ishikawa,Harvey R. Herschman,Nicholas Cacalano,April D. Pyle,No-Hee Park,Anahid Jewett
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011590
Abstract: The aims of this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. Increased cytotoxicity and augmented secretion of IFN-γ were both observed when PBMCs or NK cells were co-incubated with primary UCLA oral squamous carcinoma stem cells (UCLA-OSCSCs) when compared to differentiated UCLA oral squamous carcinoma cells (UCLA-OSCCs). In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells. Moreover, NK cells were found to lyse human Mesenchymal Stem Cells (hMSCs), human dental pulp stem cells (hDPSCs) and human induced pluripotent stem cells (hiPSCs) significantly more than their differentiated counterparts or parental lines from which they were derived. It was also found that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 in monocytes significantly augmented NK cell cytotoxicity and secretion of IFN-γ. Taken together, these results suggest that stem cells are significant targets of the NK cell cytotoxicity. However, to support differentiation of a subset of tumor or healthy untransformed primary stem cells, NK cells may be required to lyse a number of stem cells and/or those which are either defective or incapable of full differentiation in order to lose their cytotoxic function and gain the ability to secrete cytokines (split anergy). Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells.
Prevalence of kala-azar infection in Pokot county, Amudat district, Northeastern Uganda  [PDF]
Walter D. Odoch, Joseph O. Olobo
Open Journal of Epidemiology (OJEpi) , 2013, DOI: 10.4236/ojepi.2013.34029
Abstract: Introduction: Visceral leishmaniasis (kala-azar) caused by Leishmania donovani and transmitted by the sand-fly Phlebotomus martini is endemic in certain foci in north-eastern Uganda where it is thought to be confined to Pokot county, Amudat district. Amudat hospital records (April 1998-March 1999) indicated that kala-azar accounted for about 17% of hospital in-patients. However the actual prevalence of kala-azar infection in the community in Pokot county is unknown. This lack of information limits efforts geared towards its control. Objective: To determine the prevalence of kala-azar infection in Pokot county. Methods: A cross-sectional study was conducted in Pokot county in March 2010. The study participants were ≥ 5 years and were randomly selected from the age and sex strata in the chosen clusters. A questionnaire that elicited demographic profiles of participants was used for data collection. Standard procedure for direct agglutination test using blood samples collected from participants on blotting papers was performed. Data was entered in EPIINFO 3.3 and exported to STATA 10, where descriptive statistics were generated. Results: The overall prevalence of kala-azar infection in Pokot county was 17.2% but the prevalence of symptomatic infection in the community was 2.5%. The ratio of symptomatic to asymptomatic kala-azar was 1:6. Loroo sub-county had the highest prevalence of kala-azar infection followed by Karita and Amudat sub-counties at 31.9%, 14.6% and 5.3%, respectively. Conclusion: With kala-azar infection prevalence at 17.2% in the community, there is an urgent need to institute control program spearheaded by ministry of health, in the region. Furthermore, recent reports of cases from other districts within the region, the heterogeneous distribution of infection within the county and the current risk factors, including the role of animals in kala-azar transmission in this area need to be evaluated.


Oseltamivir Is Adequately Absorbed Following Nasogastric Administration to Adult Patients with Severe H5N1 Influenza
Walter R. J. Taylor, Bui Nghia Thinh, Giang Thuc Anh, Peter Horby, Heiman Wertheim, Niklas Lindegardh, Menno D. de Jong, Kasia Stepniewska, Tran Thuy Hanh, Nguyen Duc Hien, Ngo Minh Bien, Ngo Quy Chau, Annette Fox, Nghiem My Ngoc, Martin Crusat, Jeremy J. Farrar, Nicholas J. White, Nguyen Hong Ha, Trinh Thi Lien, Nguyen Vu Trung, Nicholas Day, Nguyen Gia Binh
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003410
Abstract: In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC0–12 values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC50 (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy.
New Formulation of Paraquat: A Step Forward but in the Wrong Direction?
D. Nicholas Bateman
PLOS Medicine , 2008, DOI: 10.1371/journal.pmed.0050058
Foundation Myth as legal formant: The medieval Law Merchant and the new Lex Mercatoria
Nicholas H. D. Foster
Forum Historiae Iuris , 2005,
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