Development of a Cell-based Neutralizing Antibody Assay for Zinpentraxin Alfa: Challenges and Mitigation Strategies.

Therapeutic protein drugs can potentially induce immune responses in patients and result in the production of anti-drug antibodies (ADAs), including a subset of ADAs called neutralizing antibodies (NAbs) that might cause loss of efficacy by inhibiting clinical activities of the drug. Herein, we describe the unique challenges encountered during the development of a fit-for-purpose cell-based NAb assay for a new protein modality, zinpentraxin alfa, including our strategies for assay design to overcome various matrix interferences and improve assay drug tolerance. We demonstrated that a typical biotin-drug extraction with acid dissociation (BEAD) approach alone was not sufficient to eliminate matrix interferences in this assay.

FIRST REPORTS OF LIGULA INTESTINALIS AND A SCHISTOCEPHALUS SP. INFECTING SMALL-BODIED FISH IN NEW BRUNSWICK, CANADA.

Morphological characteristics and DNA sequencing were used to identify plerocercoids of a Schistocephalus sp. infecting slimy sculpin (Cottus cognatus) from northern New Brunswick and plerocercoids of Ligula intestinalis infecting blacknose dace (Rhinichthys atratulus) in Fundy National Park (FNP, New Brunswick). To our knowledge, no previous publications documented either cestode from New Brunswick, Canada.

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

Background: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI.

Methods: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older.

Impurities in Oligonucleotide Drug Substances and Drug Products.

This white paper, which is the 10th in a series intended to address issues associated with the development of therapeutic oligonucleotides, examines the subject of product-related impurities. The authors consider chemistry and safety aspects and advance arguments in favor of platform approaches to impurity identification and qualification. Reporting, identification, and qualification thresholds suitable for product-related impurities of therapeutic oligonucleotides are proposed.

Derivation and validation of a universal vital assessment (UVA) score: a tool for predicting mortality in adult hospitalised patients in sub-Saharan Africa.

Background: Critical illness is a leading cause of morbidity and mortality in sub-Saharan Africa (SSA). Identifying patients with the highest risk of death could help with resource allocation and clinical decision making. Accordingly, we derived and validated a universal vital assessment (UVA) score for use in SSA.

Effect of an Early Resuscitation Protocol on In-hospital Mortality Among Adults With Sepsis and Hypotension: A Randomized Clinical Trial.

Importance: The effect of an early resuscitation protocol on sepsis outcomes in developing countries remains unknown.

Objective: To determine whether an early resuscitation protocol with administration of intravenous fluids, vasopressors, and blood transfusion decreases mortality among Zambian adults with sepsis and hypotension compared with usual care.

Design, Setting, And Participants: Randomized clinical trial of 212 adults with sepsis (suspected infection plus ≥2 systemic inflammatory response syndrome criteria) and hypotension (systolic blood pressure ≤90 mm Hg or mean arterial pressure ≤65 mm Hg) presenting to the emergency department at a 1500-bed referral hospital in Zambia between October 22, 2012, and November 11, 2013.

Nonacademic Attributes Predict Medical and Nursing Student Intentions to Emigrate or to Work Rurally: An Eight-Country Survey in Asia and Africa.

AbstractWe sought to identify independent, nonacademic predictors of medical and nursing student intent to migrate abroad or from rural to urban areas after graduation in low- and middle-income countries (LMIC). This was a cross-sectional survey of 3,199 first- and final-year medical and nursing students at 16 training institutions in eight LMIC. Questionnaires assessed demographics, career intentions, and preferences regarding selected career, location, and work-related attributes.

High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV-infected patients with severe sepsis in Lusaka, Zambia.

Tuberculosis is recognised as one of the leading causes of severe sepsis among HIV-infected patients. Most patients with Mycobacterium tuberculosis bacteraemia have advanced HIV disease with CD4 counts less than 100 cells/μl and its presentation is non-specific in most instances. This was a cross-sectional study which was done by analyzing data from 201 adult HIV-infected patients who met the inclusion criteria for severe sepsis.

How we implemented an analytical support clinic to strengthen student research capacity in Zambia.

Background: Research outputs in sub-Saharan Africa may be limited by a scarcity of clinical research expertise. In Zambia, clinical and biomedical postgraduate students are often delayed in graduation due to challenges in completing their research dissertations. We sought to strengthen institutional research capacity by supporting student and faculty researchers through weekly epidemiology and biostatistics clinics.

Simplified severe sepsis protocol: a randomized controlled trial of modified early goal-directed therapy in Zambia.

Objective: To assess the efficacy of a simple, goal-directed sepsis treatment protocol for reducing mortality in patients with severe sepsis in Zambia.

Design: Single-center nonblinded randomized controlled trial.

Setting: Emergency department, ICU, and medical wards of the national referral hospital in Lusaka, Zambia.

Strengthening faculty recruitment for health professions training in basic sciences in Zambia.

Zambia is facing a crisis in its human resources for health, with deficits in the number and skill mix of health workers. The University of Zambia School of Medicine (UNZA SOM) was the only medical school in the country for decades, but recently it was joined by three new medical schools--two private and one public. In addition to expanding medical education, the government has also approved several allied health programs, including pharmacy, physiotherapy, biomedical sciences, and environmental health.

Some hazards are more attractive than others: drivers of varying experience respond differently to different types of hazard.

The ability to detect hazards in video clips of driving has been inconsistently linked to driving experience and skill. One potential reason for the lack of consistency is the failure to understand the structural differences between those hazards that discriminate between safe and unsafe drivers, and those that do not. The current study used a car simulator to test drivers of differing levels of experience on approach to a series of hazards that were categorized a priori according to their underlying structure.

The Etiology And Outcome Of Adult Patients Presenting With Sepsis To The University Teaching Hospital, Lusaka, Zambia.

Background: Sepsis accounts for a significant burden of morbidity and mortality.In developed world, it is implicated as the second leading cause of non-cardiac death. Mortality from sepsis is on the increase with a mortality rate of 33-61%.

Running over unknown rough terrain with a one-legged planar robot.

The ability to traverse unknown, rough terrain is an advantage that legged locomoters have over their wheeled counterparts. However, due to the complexity of multi-legged systems, research in legged robotics has not yet been able to reproduce the agility found in the animal kingdom. In an effort to reduce the complexity of the problem, researchers have developed single-legged models to gain insight into the fundamental dynamics of legged running.

Commentary training improves responsiveness to hazards in a driving simulator.

Can commentary driving produce safer drivers? Producing a verbal commentary of potential hazards during driving has long been considered by the police to improve hazard perception skills. In this study we investigated whether learner drivers would benefit from being trained to produce a commentary drive. All learners were initially assessed on a virtual route in a driving simulator that contained 9 hazards.

Prevalence and Factors Associated with Renal Dysfunction in HIV Positive and Negative Adults at the University Teaching Hospital, in Lusaka.

Background: Despite having the highest disease burden of HIV, Sub-Saharan Africa has limited data on HIV related kidney disease with most available data coming from the developed countries. Kidney disease is a recognised complication in HIV infected patients presenting with acute renal failure (ARF) or chronic kidney disease (CKD). This study investigated the prevalence and risk factors associated with renal dysfunction among hospitalised HIV infected patients at the University Teaching Hospital (UTH), Lusaka.

HIV/AIDS and Postnatal Depression at the University Teaching Hospital, Lusaka, Zambia.

OBJECTIVE: To study the contribution of HIV/AIDS to the problem of postnatal depression among women receiving postnatal care at University Teaching Hospital (UTH), Lusaka, Zambia. BACKGROUND: Postnatal depression (PND), a major depressive episode during the puerperium, affects between 10% and 22% of adult women before the infant's first birthday. HIV seropositivity has been associated with increased risk of mental disease, but its influence on postnatal depression has not been fully explored.

Performance of modified WHO presumptive criteria for diagnosis of HIV infection in children <18 months admitted to University Teaching Hospital in Lusaka.

BACKGROUND: Making a diagnosis of HIV infection in children aged less than 18 months remains a challenge in low resource settings like Zambia due to the limited availability of gold standard testing with HIV DNA PCR. Clinicians in rural areas have to depend on clinical diagnosis to start HAART as they wait for the dry blood spot (DBS) for DNA PCR results sent from the urban centers. METHODS: This descriptive cross-sectional study was performed at the University Teaching Hospital, Lusaka, Zambia.

Association of pre- and postoperative plasma levels of transforming growth factor beta(1) and interleukin 6 and its soluble receptor with prostate cancer progression.

Purpose: We have shown that preoperative plasma levels of transforming growth factor-beta(1) (TGF-beta(1)), interleukin 6 (IL)-6, and its receptor (IL-6sR) are associated with prostate cancer progression and metastasis. The objectives of this study were to confirm these findings and to examine the association of changes in plasma levels of these markers after surgery with disease progression in a large consecutive cohort of patients.

Experimental Design: Plasma levels of TGF-beta(1), IL-6, and IL-6sR were measured pre- and postoperatively (6-8 weeks after surgery) in 302 consecutive patients who underwent radical prostatectomy for clinically localized disease.

The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer.

Purpose: Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1).

Association of plasma urokinase-type plasminogen activator and its receptor with clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder.

Objectives: The urokinase plasminogen activation (uPA) system plays an important role in tumor invasion and metastasis by mediating proteolysis, adhesion, and migration of tumor cells. We tested the hypothesis that preoperative plasma levels of uPA and its specific receptor, uPAR, would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder.

Methods: The study group consisted of 51 patients who underwent radical cystectomy for muscle-invasive cancer or Tis, Ta, or T1 transitional cell carcinoma refractory to intravesical therapy and 44 men without cancer.