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As countries across sub-Saharan Africa work towards universal health coverage and HIV epidemic control, investments seek to bolster the quality and relevance of the health workforce. The African Health Profession Regulatory Collaborative (ARC) partnered with 17 countries across East, Central, and Southern Africa to ensure nurses and midwives were authorized and equipped to provide essential HIV services to pregnant women and children with HIV. Through ARC, nursing leadership teams representing each country identify a priority regulatory function and develop a proposal to strengthen that regulation over a 1-year period. Each year culminates with a summative congress meeting, involving all ARC countries, where teams present their projects and share lessons learned with their colleagues. During a recent ARC Summative Congress, a group survey was administered to 11 country teams that received ARC Year 4 grants to measure advancements in regulatory function using the five-stage Regulatory Function Framework, and a group questionnaire was administered to 16 country teams to measure improvements in national nursing capacity (February 2011–2016). In ARC Year 4, eight countries implemented continuing professional development projects, Botswana revised their scope of practice, Mozambique piloted a licensing examination to assess HIV-related competencies, and South Africa developed accreditation standards for HIV/tuberculosis specialty nurses. Countries reported improvements in national nursing leaders’ teamwork, collaborations with national organizations, regional networking with nursing leaders, and the ability to garner additional resources. ARC provides an effective, collaborative model to rapidly strengthen national regulatory frameworks, which other health professional cadres or regions may consider using to ensure a relevant health workforce, authorized and equipped to meet the emerging demand for health services.

Objective. Keliximab studies have provided evidence of the therapeutic potential of a non‐depleting CD4 monoclonal antibody (mAb) in the treatment of rheumatoid arthritis (RA). Clenoliximab, an immunoglobulin G4 derivative of keliximab, has substantially reduced potential to deplete CD4 cells. In initial studies of clenoliximab, we investigated the hypothesis that the decrease in cell surface CD4 is the result of antibody‐mediated stripping from the cell surface.Methods. Patients received single or multiple intravenous infusions of clenoliximab as follows: 0.05, 0.2, 1, 5, 10 or 15 mg/kg (n=3–5/group); 150 or 350 mg weekly×4; or 350 or 700 mg every other week×2 (n=12/group). Blood was collected for up to 16 weeks and pharmacokinetic and pharmacodynamic assessments were conducted using immunoassay and flow cytometry.Results. CD4 count was largely unaffected by clenoliximab treatment. Dose‐dependent CD4 coating, down‐modulation and stripping were observed. Maximal down‐modulation persisted for an increasing period as dose increased, while soluble CD4–clenoliximab complexes accumulated. The amount of CD4 in soluble complex was as much as 20 times the amount of cell‐associated CD4. For the same total dose, administration of higher doses, less frequently, resulted in pharmacodynamic profiles similar to those of lower doses administered more frequently.Conclusion. Decrease in the density of CD4 on the T‐lymphocyte surface is caused by antibody‐mediated stripping.

This descriptive exploratory study used thematic analysis to interpret short videotaped speech samples produced by persons with dementia in response to the question, “How have things been going for you lately?” The researchers were able to identify themes in 50 of the 56 interviews with men and women with Mini-Mental State Examination (MMSE) scores that ranged from five to 28. The major themes across all MMSE levels were losses, feelings about losses, and attempts to manage losses. The individuals’ choice of themes as well as their verbal and nonverbal expressions suggested that they were experiencing a significant amount of stress, especially related to their relationships with family and friends.

The pharmacokinetics and tissue distribution of SB-251353, a novel truncated form of the human CXC chemokine growth-related gene product beta, were studied after intravenous administration to the mouse (0.1–250 mg/kg). At the lowest dose, the clearance exceeded blood flow to the kidney. As the dose increased, clearance approached the glomerular filtration rate in the mouse. Clearance of this chemokine may be mediated by its pharmacologic receptor, CXCR2, via endocytosis with subsequent lysosomal degradation, as has been observed for several growth and hematopoietic factors. Apparent distribution volumes were high (≥1 l/kg). Moderate binding to the Duffy antigen/receptor for chemokines on erythrocytes was observed. Consistent with the pharmacokinetic analysis, microscopic autoradiography showed uptake into renal proximal tubule epithelial cells. Limited excretion of SB-251353 in the urine (<2%) was consistent with catabolism of the chemokine in the tubules. Binding to hepatic sinusoids and connective tissue in the dermis was observed. This possibly reflected interaction of SB-251353 with heparin sulfate proteoglycan and may explain the large distribution volumes. This first study of the disposition of a chemokine provides insight into mechanism of action and physiological factors that may influence chemokine pharmacodynamics.

We present the first threshold ion-pair production spectrum of a triatomic molecule. We have recorded the ion-pair yield spectrum and TIPP spectrum for the H2S → H⁺+SH^- ion-pair channel using single-photon excitation. From the TIPP spectrum, we have determined the H−SH bond energy (31451 ± 4 cm^-1) to unprecedented accuracy and demonstrated the formation of weakly bound H⁺−SH^- (J‘) ion-pair states, with rotational excitation of the SH^- anion up to J‘ = 4. The bound nature of these states, and the assigned spectrum that results from their field dissociation suggests that this technique can be applied to many other triatomic and larger polyatomic molecules in the future, leading to energetic, spectroscopic, and dynamical information about these species.

Recombinant soluble CD4 (sT4; mol. wt. 45,000) has been studied extensively in Sprague-Dawley rats, and substantial renal processing has been indicated. In rats and monkeys, renal filtration and precipitation of sT4 in the distal nephron caused tubular cast nephropathy. Intravenous pharmacokinetics in the rat demonstrated that sT4 plasma clearance exceeded the glomerular filtration rate. In an effort to determine quantitatively the extent to which kidney and other tissues were responsible for sT4 catabolism, sT4 was labeled with trace amounts of dilactitol-[125I]tyramine and administered intravenously to Sprague-Dawley rats (1 mg/kg). Dilactitol-tyramine accumulates in lysosomes at the site of protein degradation. It has been used primarily to demonstrate hepatic catabolism of endogenous proteins. Blood samples were drawn for pharmacokinetic analysis, and selected tissues were removed to assess radiolabel distribution. Comparison of pharmacokinetic parameters derived from total plasma radiolabel and functional ELISA were not significantly different. Thus, covalent modification of sT4 with dilactitol-tyramine did not appreciably change the rate of clearance. From 3 to 24 hr after intravenous administration, 81.5 +/- 0.1% of the total administered radioactivity was found in the kidney. Approximately 8-13% of the administered dose was recovered in the liver. Macroscopic autoradiography of the kidney demonstrated accumulation of radiolabel in the cortex. Light microscopic autoradiography of the kidney following intravenous administration of directly radioiodinated sT4 confirmed cortical processing, because radiolabel was located primarily in epithelial cells of P1 and P2 segments of the proximal tubule after low intravenous doses (0.4-4 mg/kg). At 40 mg/kg, distal tubules and cortical collecting ducts were labeled as well. Thus, sT4 was filtered by the glomerulus, reabsorbed in the proximal tubule, and degraded in the lysosomal compartment.

A preclinical evaluation of RSHZ19, a respiratory syncytial virus-specific reshaped human monoclonal antibody (IgG1 framework), has included pharmacokinetic studies in rats, adult cynomolgus macaques, and infant baboons after intravenous (iv), subcutaneous, or intramuscular (im) administration. After iv administration to rats and monkeys (1 mg/kg dose), a biphasic decline in plasma concentration was observed. The dominant terminal phase was characterized by an 11-day half-life in rats and a 21- to 24-day half-life in monkeys. Plasma clearances of 0.3 ml/hr/kg in the rat and 0.1-0.2 ml/hr/kg in the monkey were estimated. In the macaque, based on area under the curve, no evidence of significant nonlinearity in the pharmacokinetics was observed over a 200-fold dose range (1-200 mg/kg). In rat and monkey, absorption after extravascular administration was rapid relative to elimination (apparent half-lives < or = 24 hr), and bioavailability was high (> or = 82%). After iv or im administration to macaques (> or = 40 mg/kg), 1 of 3 animals in each group developed anti-RSHZ19 antibodies, and this resulted in rapid elimination of RSHZ19 from plasma. After the administration of a second im dose to macaques, no additional animals developed anti-RSHZ19 antibodies. Multiple-dose iv kinetics (5-day repeat dose) in infant baboons were modeled accurately by adult macaque data, suggesting that these species handled RSHZ19 similarly. The pharmacokinetic characteristics of RSHZ19 should support a convenient regimen for treatment or prophylaxis of human respiratory syncytial virus infection.

Physician involvement in home care has declined markedly over the past 50 years. By contrast, the renaissance in home care in the US over the last decade has created a pressing need for greater physician participation and new roles for physicians as members of the home care team. This article reviews these developments and identifies the need for improved medical education and physician reimbursement if the desired physician involvement in home care is to become a reality.

Families and friends provide most of the chronic care for dementia patients. The impact of caregiving on caregivers, as well as the training and informational needs of caregivers will vary substantially, depending on the underlying cause of the dementia. Clinicians can provide these caregivers with support and training but must assess both the nature of the caregiving burden and the capacity of the caregiver to provide care. This article provides a review of the literature on the impact of caring for Alzheimer’s patients and suggests how impact can vary widely by examining caregiving in six other dementing conditions.

A new experimental apparatus is described which permits the determination of binding energetics for metal−ligand complexes. This technique mates laser ablation for the generation of atomic metal ions with the environment of a high-pressure ion source which leads to rapid termolecular stabilization of metal ion-ligand complexes containing one or more ligands. The time resolved capability of the detection system allows equilibrium to be studied quantitatively for binding energies in the range of 5−30 kcal mol^-1. Such measurements of the absolute binding energy of formaldehyde to Al⁺ combined with existing bimolecular Al⁺ exchange equilibrium data leads to an absolute Al⁺ affinity scale. For two ligand complexes an extensive ab initio search of the potential energy surfaces shows that the experimentally observed species involving CH3CN and (CH3)2O involve simple ligand complexation with an acute L-Al−L bond angle (L = ligand) rather than hydrogen bonded or inserted structures. In one instance a third ligand complexation has been experimentally investigated likely leading to a species of pyramidal geometry.

Methods of generating coherent vacuum ultraviolet radiation by frequency mixing techniques are reviewed. The theory and methodology of four‐wave mixing in gas mixtures is discussed and some representative methods for generating coherent light in the range from 900 Å to 2000 Å are described. In the last section some recent applications of these VUV sources to chemical physics will be outlined.

To examine the issues concerning Rydberg-state stabilization in pulsed-field ionization zero-kinetic-energy (PFI-ZEKE) photoelectron spectroscopy, spectra at the first and second ionization thresholds of argon have been taken under different ion-density conditions. These provide a contrast between the signals from autoionizing and nonautoionizing Rydberg series. A careful comparison between the PFI-ZEKE spectra and relative partial photoionization cross sections provides the first measurement of the efficiency of stabilization in PFI-ZEKE spectroscopy. This efficiency or quantum yield varies at the second ionization threshold with changing ion density and principal quantum number, introducing ion-density-dependent line-shape distortions. These changes may be ascribed to the competition between stabilization and autoionization of the Rydberg states and its variation with principal quantum number.