Toxicity-related antiretroviral drug treatment modifications in individuals starting therapy: a cohort analysis of time patterns, sex, and other risk factors.

BackgroundModifications to combination antiretroviral drug therapy (CART) regimens can occur for a number of reasons, including adverse drug effects. We investigated the frequency of and reasons for antiretroviral drug modifications (ADM) during the first 3 years after initiation of CART, in a closed cohort of CART-naïve adult patients who started treatment in the period 1998-2007 in Croatia.Material and methodsWe calculated differential toxicity rates by the Poisson method. In multivariable analysis, we used a discrete-time regression model for repeated events for the outcome of modification due to drug toxicity.ResultsOf 321 patients who started CART, median age was 40 years, 19% were women, baseline CD4 was <200 cells/mm3 in 71%, and viral load was ≥100 000 copies/mL in 69%. Overall, 220 (68.5%) patients had an ADM; 124 (56%) of these had ≥1 ADM for toxicity reasons. Only 12.7% of individuals starting CART in the period 1998-2002 and 39.4% in the period 2003-2007 remained on the same regimen after 3 years. The following toxicities caused ADM most often: lipoatrophy (22%), gastrointestinal symptoms (20%), and neuropathy (18%). Only 5% of drug changes were due to virologic failure. Female sex (hazard ratio [HR], 2.42 95%; confidence intervals, 1.39-4.24) and older age (HR, 1.42 per every 10 years) were associated with toxicity-related ADM in the first 3 months of a particular CART regimen, but after 3 months of CART they were not.ConclusionsLess toxic and better-tolerated HIV treatment options should be available and used more frequently in Croatia

The geometry of reaction norms yields insights on classical fitness functions for Great Lakes salmon.

Life history theory examines how characteristics of organisms, such as age and size at maturity, may vary through natural selection as evolutionary responses that optimize fitness. Here we ask how predictions of age and size at maturity differ for the three classical fitness functions-intrinsic rate of natural increase r, net reproductive rate R0, and reproductive value Vx-for semelparous species. We show that different choices of fitness functions can lead to very different predictions of species behavior. In one's efforts to understand an organism's behavior and to develop effective conservation and management policies, the choice of fitness function matters. The central ingredient of our approach is the maturation reaction norm (MRN), which describes how optimal age and size at maturation vary with growth rate or mortality rate. We develop a practical geometric construction of MRNs that allows us to include different growth functions (linear growth and nonlinear von Bertalanffy growth in length) and develop two-dimensional MRNs useful for quantifying growth-mortality trade-offs. We relate our approach to Beverton-Holt life history invariants and to the Stearns-Koella categorization of MRNs. We conclude with a detailed discussion of life history parameters for Great Lakes Chinook Salmon and demonstrate that age and size at maturity are consistent with predictions using R0 (but not r or Vx) as the underlying fitness function

Treatment of Scarlatina.

n/

The Pandemic and its Impacts

The Pandemic has a long history, but the term of “pandemic” is still not been defined by many medical texts. There have been many significant pandemics recorded in human history, and the pandemic related crises have caused enormous negative impacts on health, economies, and even national security in the world. This article will explore the literature for the concept and history of pandemics; summarises the key features of a pandemics, and discusses the negative impacts on health, economy, social and global security of pandemics and disease outbreaks

Challenges to generating political prioritization for adolescent sexual and reproductive health in Kenya: A qualitative study.

BackgroundDespite the high burden of adverse adolescent sexual and reproductive health (SRH) outcomes, it has remained a low political priority in Kenya. We examined factors that have shaped the lack of current political prioritization of adolescent SRH service provision.MethodsWe used the Shiffman and Smith policy framework consisting of four categories-actor power, ideas, political contexts, and issue characteristics-to analyse factors that have shaped political prioritization of adolescent SRH. We undertook semi-structured interviews with 14 members of adolescent SRH networks between February and April 2019 at the national level and conducted thematic analysis of the interviews.FindingsSeveral factors hinder the attainment of political priority for adolescent SRH in Kenya. On actor power, the adolescent SRH community was diverse and united in adoption of international norms and policies, but lacked policy entrepreneurs to provide strong leadership, and policy windows were often missed. Regarding ideas, community members lacked consensus on a cohesive public positioning of the problem. On issue characteristics, the perception of adolescents as lacking political power made politicians reluctant to act on the existing data on the severity of adolescent SRH. There was also a lack of consensus on the nature of interventions to be implemented. Pertaining to political contexts, sectoral funding by donors and government treasury brought about tension within the different government ministries resulting in siloed approaches, lack of coordination and overall inefficiency. However, the SRH community has several strengths that augur well for future political support. These include the diverse multi-sectoral background of its members, commitment to improving adolescent SRH, and the potential to link with other health priorities such as maternal health and HIV/AIDS.ConclusionIn order to increase political attention to adolescent SRH in Kenya, there is an urgent need for policy actors to: 1) create a more cohesive community of advocates across sectors, 2) develop a clearer public positioning of adolescent SRH, 3) agree on a set of precise approaches that will resonate with the political system, and 4) identify and nurture policy entrepreneurs to facilitate the coupling of adolescent SRH with potential solutions when windows of opportunity arise

Observing the spin of a free electron

Long ago, Bohr, Pauli, and Mott argued that it is not, in principle, possible to measure the spin components of a free electron. One can try to use a Stern-Gerlach type of device, but the finite size of the beam results in an uncertainty of the splitting force that is comparable with the gradient force. The result is that no definite spin measurement can be made. Recently there has been a revival of interest in this problem, and we will present our own analysis and quantum-mechanical wave-packet calculations which suggest that a spin measurement is possible for a careful choice of initial conditions

Systematic review of the behavioural assessment of pain in cats

Objectives The objectives were to review systematically the range of assessment tools used in cats to detect the behavioural expression of pain and the evidence of their quality; and to examine behavioural metrics (considering both the sensory and affective domains) used to assess pain. Methods A search of PubMed and ScienceDirect, alongside articles known to the authors, from 2000 onwards, for papers in English was performed. This was followed by a manual search of the references within the primary data sources. Only peer-reviewed publications that provided information on the assessment tool used to evaluate the behavioural expression of pain in cats, in conscious animals (not anaesthetised cats), were included. Results No previous systematic reviews were identified. One hundred papers were included in the final assessment. Studies were primarily related to the assessment of pain in relation to surgical procedures, and no clear distinction was made concerning the onset of acute and chronic pain. Ten broad types of instrument to assess pain were identified, and generally the quality of evidence to support the use of the various instruments was poor. Only one specific instrument (UNESP-Botucatu scale) had published evidence of validity, reliability and sensitivity at the level of a randomised control trial, but with a positive rather than placebo control, and limited to its use in the ovariohysterectomy situation. The metrics used within the tools appeared to focus primarily on the sensory aspect of pain, with no study clearly discriminating between the sensory and affective components of pain. Conclusions and relevance Further studies are required to provide a higher quality of evidence for methods used to assess pain in cats. Furthermore, a consistent definition for acute and chronic pain is needed. Tools need to be validated that can detect pain in a range of conditions and by different evaluators (veterinary surgeons and owners), which consider both the sensory and emotional aspects of pain

Relativistic precession and spin dynamics of an elliptic Rydberg wave packet

Time evolution of wave packets built from the eigenstates of the Dirac equation for a hydrogenic system is considered. We investigate the space and spin motion of wave packets which, in the non-relativistic limit, are stationary states with a probability density distributed uniformly along the classical, elliptical orbit (elliptic WP). We show that the precession of such a WP, due to relativistic corrections to the energy eigenvalues, is strongly correlated with the spin motion. We show also that the motion is universal for all hydrogenic systems with an arbitrary value of the atomic number Z.Comment: Latex2e, uses IOP style files (included), 10 pages, 5 jpg figures, 1 postscript figure. Relation between precession time and radiative liftime added (eq.(12)). Accepted for publication in J. Phys.

Subsystems of a finite quantum system and Bell-like inequalities

YesThe set of subsystems Sigma(m) of a finite quantum system Sigma(n) with variables in Z(n) together with logical connectives, is a Heyting algebra. The probabilities tau(m vertical bar rho(n)) Tr vertical bar B(m)rho(n)] (where B(m) is the projector to Sigma(m)) are compatible with associativity of the join in the Heyting algebra, only if the variables belong to the same chain. Consequently, contextuality in the present formalism, has the chains as contexts. Various Bell-like inequalities are discussed. They are violated, and this proves that quantum mechanics is a contextual theory