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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1995.Includes bibliographical references (leaves 42-43).by Bruce R. Krysiak.M.Eng

Hydration effects turn a highly stretched polymer from an entropic into an energetic spring

Polyethylene glycol (PEG) is a structurally simple and nontoxic water-soluble polymer that is widely used in medical and pharmaceutical applications as molecular linker and spacer. In such applications, PEG’s elastic response against conformational deformations is key to its function. According to text-book knowledge, a polymer reacts to the stretching of its end-to-end separation by a decrease in entropy that is due to the reduction of available conformations, which is why polymers are commonly called entropic springs. By a combination of single-molecule force spectroscopy experiments with molecular dynamics simulations in explicit water, we show that entropic hydration effects almost exactly compensate the chain conformational entropy loss at high stretching. Our simulations reveal that this entropic compensation is due to the stretching-induced release of water molecules that in the relaxed state form double hydrogen bonds with PEG. As a consequence, the stretching response of PEG is predominantly of energetic, not of entropic, origin at high forces and caused by hydration effects, while PEG backbone deformations only play a minor role. These findings demonstrate the importance of hydration for the mechanics of macromolecules and constitute a case example that sheds light on the antagonistic interplay of conformational and hydration degrees of freedom

Pathologically confirmed breast cancer in Malawi: a descriptive study: Clinical profile of breast cancer

Background: Breast cancer is the most common female cancer in Africa, yet no published studies have investigated breast cancer in Malawi. Understanding the clinical profile of breast cancer is important to develop early diagnosis efforts.Aim: To describe clinical and pathological characteristics of breast specimens from a pathology laboratory at a national teaching hospital.Methods: Secondary analysis of pathology reports from July 2011 to September 2013.Results: Among 85 breast cancer cases, 55% were < 50 years. Median tumor size was 4 cm and 49% were grade 3. Median symptom duration was eight months.Conclusions: Malawian women with breast cancer commonly have long symptom durations prior to diagnosis, young age, and poorly differentiated tumors. Improved clinical and pathological characterization, including hormone receptor status, are urgently needed to better understand this disease in Malawi

Causes of cervical lymphadenopathy at Kamuzu Central Hospital

AimDescription of pathologic causes of cervical lymphadenopathy at Kamuzu Central Hospital.IntroductionThe evaluation of cervical lymphadenopathy is a common diagnostic challenge facing clinicians. Previously at Kamuzu Central Hospital (KCH) tuberculosis (TB) was reported to be the most common cause of cervical lymphadenopathy However, no recent study has assessed this common diagnostic challenge in Malawi, particularly since the beginning of the HIV epidemic and the subsequent scale-up of antiretroviral therapy.MethodsWe conducted a cross-sectional study of all cervical lymph node specimens from the KCH pathology laboratory between 1 July 2011 and 28 February 2013 and describe patient age, gender, and pathologic diagnoses.ResultsOur search of the KCH pathology database yielded 179 cases. Of these, 143 (77%) were histologic specimens (open biopsy or core needle samples) while 34 (23%) were cytology specimens. The age range was from 0 to 76 years with a mean of 30 (SD: 19). In adults, the most common diagnosis was malignancy (n=41, 35%), while in children 15 cases each of malignancy and benign masses were diagnosed. Only 6 cases (5%) of TB were diagnosed in adults, and 4 cases (6%) of TB were diagnosed in children.ConclusionOur study shows more malignancy and much less TB than a prior study of cervical lymphadenopathy at KCH. With the successful initiaion of the KCH Pathology Laboratory in 2011, we recommend biopsy or FNA early in the workup of cervical lymphadenopathy to prevent long delays in diagnosis and treatment of curable cancers

Colonization with Multidrug-Resistant Enterobacteriaceae is Associated with Increased Mortality Following Burn Injury in Sub-Saharan Africa

Background: Multidrug-resistant (MDR) bacteria are an emerging international concern in low- and middle-income countries that threaten recent public health gains. These challenges are exacerbated in immunocompromised hosts, such as those with burn injury. This study sought to describe the epidemiology and associated clinical outcomes of burn wound colonization in a Malawian tertiary burn center. Methods: This is a prospective analysis of burn patients presenting to Kamuzu Central Hospital in Lilongwe, Malawi, within 72 h of burn injury. A swab of each patient’s primary wound was collected at admission and each subsequent week. The primary exposure was burn wound colonization with MDR bacteria, particularly Enterobacteriaceae. The primary outcome was in-hospital mortality. A log binomial model estimated the association between the exposure and outcome, adjusted for confounders. Results: Ninety-nine patients were enrolled with a median age of 4 years (IQR 2–12) and a male preponderance (54%). Median total body surface area burn (TBSA) was 14% (IQR 9–25), and crude in-hospital mortality was 19%. Enterobacteriaceae were the most common MDR bacteria with 36% of patients becoming colonized. Wound colonization with MDR Enterobacteriaceae was associated with increased in-hospital mortality with a risk ratio of 1.86 (95% CI 1.38, 2.50, p < 0.001) adjusted for TBSA, burn type (scald vs. flame), sex, age, length of stay, and methicillin-resistant Staphylococcus aureus colonization. Conclusion: MDR bacteria, especially Enterobacteriaceae, are common and are associated with worse burn injury outcomes. In resource-poor environments, a greater emphasis on prevention of MDR bacterial colonization, improved isolation precautions, affordable diagnostics, and antibiotic stewardship are imperative

Causes of cervical lymphadenopathy at Kamuzu Central Hospital

Aim: Description of pathologic causes of cervical lymphadenopathy at Kamuzu Central Hospital. Introduction: The evaluation of cervical lymphadenopathy is a common diagnostic challenge facing clinicians. Previously at Kamuzu Central Hospital (KCH) tuberculosis (TB) was reported to be the most common cause of cervical lymphadenopathy However, no recent study has assessed this common diagnostic challenge in Malawi, particularly since the beginning of the HIV epidemic and the subsequent scale-up of antiretroviral therapy. Methods: We conducted a cross-sectional study of all cervical lymph node specimens from the KCH pathology laboratory between 1 July 2011 and 28 February 2013 and describe patient age, gender, and pathologic diagnoses. Results: Our search of the KCH pathology database yielded 179 cases. Of these, 143 (77%) were histologic specimens (open biopsy or core needle samples) while 34 (23%) were cytology specimens. The age range was from 0 to 76 years with a mean of 30 (SD: 19). In adults, the most common diagnosis was malignancy (n=41, 35%), while in children 15 cases each of malignancy and benign masses were diagnosed. Only 6 cases (5%) of TB were diagnosed in adults, and 4 cases (6%) of TB were diagnosed in children. Conclusion: Our study shows more malignancy and much less TB than a prior study of cervical lymphadenopathy at KCH. With the successful initiaion of the KCH Pathology Laboratory in 2011, we recommend biopsy or FNA early in the workup of cervical lymphadenopathy to prevent long delays in diagnosis and treatment of curable cancers

DGIdb 2.0: Mining clinically relevant drug-gene interactions

The Drug–Gene Interaction Database (DGIdb, www. dgidb.org) is a web resource that consolidates dis-parate data sources describing drug–gene interac-tions and gene druggability. It provides an intuitive graphical user interface and a documented applica-tion programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined in-formation of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. Specif-ically, nine new sources of drug–gene interactions have been added, including seven resources specifi-cally focused on interactions linked to clinical trials. These additions have more than doubled the over-all count of drug–gene interactions. The total num-ber of druggable gene claims has also increased by 30%. Importantly, a majority of the unrestricted, publicly-accessible sources used in DGIdb are now automatically updated on a weekly basis, providing the most current information for these sources. Fi-nally, a new web view and API have been developed to allow searching for interactions by drug identifiers to complement existing gene-based search function-ality. With these updates, DGIdb represents a com-prehensive and user friendly tool for mining the druggable genome for precision medicine hypothe-sis generation