Brand Personality and the Evolution of Destination Kenya during the Colonial Period

This paper offers an intellectual discourse for destination managers by exploring alternative branding approaches used during the colonial period in Kenya, now that the image is under siege both internally through socio-economic instability and unprecedented levels of poaching, and externally through travel warnings, outright trafficking in big game trophies, the constant threat of terror attacks, and poor global rankings in the Travel and Tourism Competitive Index. The paper conforms to the mission of thought and practice by identifying practical ways of promoting tourist destination Kenya through an in-depth analysis of historical experiences.   Key Words Evolutionary Stages, Big Game Hunting, Brand Personality, Brand Imag

High prevalence of curable sexually transmitted infections among pregnant women in a rural county hospital in Kilifi, Kenya.

BACKGROUND: Women attending antenatal care (ANC) in resource-limited countries are frequently screened for syphilis and HIV, but rarely for other sexually transmitted infections (STIs). We assessed the prevalence of curable STIs, defined as infection with either Chlamydia trachomatis or Neisseria gonorrhoeae or Trichomonas vaginalis, from July to September 2015. METHODS: In a cross-sectional study, women attending ANC at the Kilifi County Hospital, Kenya, had a urine sample tested for C. trachomatis/N. gonorrhoeae by GeneXpert® and a vaginal swab for T. vaginalis by culture. Bacterial vaginosis (BV) was defined as a Nugent score of 7-10 of the Gram stain of a vaginal smear in combination with self-reported vaginal discharge. Genital ulcers were observed during collection of vaginal swabs. All women responded to questions on socio-demographics and sexual health and clinical symptoms of STIs. Predictors for curable STIs were assessed in multivariable logistic regression. RESULTS: A total of 42/202 (20.8%, 95% confidence interval (CI):15.4-27.0) women had a curable STI. The prevalence was 14.9% for C. trachomatis (95% CI:10.2-20.5), 1.0% for N. gonorrhoeae (95% CI: 0.1-3.5), 7.4% for T. vaginalis (95% CI:4.2-12.0), 19.3% for BV (95% CI: 14.1-25.4) and 2.5% for genital ulcers (95% CI: 0.8-5.7). Predictors for infection with curable STIs included women with a genital ulcer (adjusted odds ratio (AOR) = 35.0, 95% CI: 2.7-461.6) compared to women without a genital ulcer, women who used water for cleaning after visiting the toilet compared to those who used toilet paper or other solid means (AOR = 4.1, 95% CI:1.5-11.3), women who reported having sexual debut ≤ 17 years compared to women having sexual debut ≥18 years (AOR = 2.7, 95% CI:1.1-6.6), and BV-positive women (AOR = 2.7, 95% CI:1.1-6.6) compared to BV-negative women. CONCLUSION: One in five women attending ANC had a curable STI. These infections were associated with genital ulcers, hygiene practices, early sexual debut and bacterial vaginosis

The use of a P. falciparum specific coiled-coil domain to construct a self-assembling protein nanoparticle vaccine to prevent malaria.

The parasitic disease malaria remains a major global public health concern and no truly effective vaccine exists. One approach to the development of a malaria vaccine is to target the asexual blood stage that results in clinical symptoms. Most attempts have failed. New antigens such as P27A and P27 have emerged as potential new vaccine candidates. Multiple studies have demonstrated that antigens are more immunogenic and are better correlated with protection when presented on particulate delivery systems. One such particulate delivery system is the self-assembling protein nanoparticle (SAPN) that relies on coiled-coil domains of proteins to form stable nanoparticles. In the past we have used de novo designed amino acid domains to drive the formation of the coiled-coil scaffolds which present the antigenic epitopes on the particle surface. Here we use naturally occurring domains found in the tex1 protein to form the coiled-coil scaffolding of the nanoparticle. Thus, by engineering P27A and a new extended form of the coiled-coil domain P27 onto the N and C terminus of the SAPN protein monomer we have developed a particulate delivery system that effectively displays both antigens on a single particle that uses malaria tex1 sequences to form the nanoparticle scaffold. These particles are immunogenic in a murine model and induce immune responses similar to the ones observed in seropositive individuals in malaria endemic regions. We demonstrate that our P27/P27A-SAPNs induce an immune response akin to the one in seropositive individuals in Burkina Faso. Since P27 is highly conserved among different Plasmodium species, these novel SAPNs may even provide cross-protection between Plasmodium falciparum and Plasmodium vivax the two major human malaria pathogens. As the SAPNs are also easy to manufacture and store they can be delivered to the population in need without complication thus providing a low cost malaria vaccine

Adjustment to acute or early HIV-1 infection diagnosis to prompt linkage to care and ART initiation: qualitative insights from coastal Kenya

Diagnosing and treating patients with acute or early HIV-1 infection (AEHI) is an important strategy to prevent HIV-1 transmission. We used qualitative methods to understand factors that facilitate adjustment to AEHI diagnosis, prompt linkage to care and initiation of antiretroviral treatment (ART). Twenty-three AEHI patients (12 women, 11 men) included 18 participants identified at health facilities, and 5 participants identified in a sex worker cohort. Of these, 17 participants (9 women, 8 men) participated in qualitative interviews about their AEHI status 2 weeks after diagnosis. Thirteen participants (7 women, 6 men) returned for a second interview 12 weeks after diagnosis. Interviews explored participants' experiences at the time of and following their diagnosis, and examined perceptions about ART initiation and behavior change recommendations, including disclosure and partner notification. A grounded theory framework was used for analysis, eliciting three important needs that should be addressed for AEHI patients: 1) the need to better understand AEHI and accept one's status; 2) the need to develop healthy strategies and adjust to the reality of AEHI status; and 3) the need to protect self and others through ART initiation, adherence, safer sex, and disclosure. A preliminary conceptual framework to guide further intervention and research with AEHI populations is proposed

Men who have sex with men sensitivity training reduces homoprejudice and increases knowledge among Kenyan healthcare providers in coastal Kenya

Introduction: Healthcare workers (HCWs) in Africa typically receive little or no training in the healthcare needs of men who have sex with men (MSM), limiting the effectiveness and reach of population‐based HIV control measures among this group. We assessed the effect of a web‐based, self‐directed sensitivity training on MSM for HCWs (www.marps‐africa.org), combined with facilitated group discussions on knowledge and homophobic attitudes among HCWs in four districts of coastal Kenya. Methods: We trained four district “AIDS coordinators” to provide a two‐day training to local HCWs working at antiretroviral therapy‐providing facilities in coastal Kenya. Self‐directed learning supported by group discussions focused on MSM sexual risk practices, HIV prevention and healthcare needs. Knowledge was assessed prior to training, immediately after training and three months after training. The Homophobia Scale assessed homophobic attitudes and was measured before and three months after training. Results: Seventy‐four HCWs (68% female; 74% clinical officers or nurses; 84% working in government facilities) from 49 health facilities were trained, of whom 71 (96%) completed all measures. At baseline, few HCWs reported any prior training on MSM anal sexual practices, and most HCWs had limited knowledge of MSM sexual health needs. Homophobic attitudes were most pronounced among HCWs who were male, under 30 years of age, and working in clinical roles or government facilities. Three months after training, more HCWs had adequate knowledge compared to baseline (49% vs. 13%, McNemar's test p<0.001); this was most pronounced in those with clinical or administrative roles and in those from governmental health providers. Compared to baseline, homophobic attitudes had decreased significantly three months after training, particularly among HCWs with high homophobia scores at baseline, and there was some evidence of correlation between improvements in knowledge and reduction in homophobic sentiment. Conclusions: Scaling up MSM sensitivity training for African HCWs is likely to be a timely, effective and practical means to improve relevant sexual health knowledge and reduce personal homophobic sentiment among HCWs involved in HIV prevention, testing and care in sub‐Saharan Africa

Computational design of therapeutic antibodies with improved developability: efficient traversal of binder landscapes and rescue of escape mutations

Developing therapeutic antibodies is a challenging endeavor, often requiring large-scale screening to produce initial binders, that still often require optimization for developability. We present a computational pipeline for the discovery and design of therapeutic antibody candidates, which incorporates physics- and AI-based methods for the generation, assessment, and validation of candidate antibodies with improved developability against diverse epitopes, via efficient few-shot experimental screens. We demonstrate that these orthogonal methods can lead to promising designs. We evaluated our approach by experimentally testing a small number of candidates against multiple SARS-CoV-2 variants in three different tasks: (i) traversing sequence landscapes of binders, we identify highly sequence dissimilar antibodies that retain binding to the Wuhan strain, (ii) rescuing binding from escape mutations, we show up to 54% of designs gain binding affinity to a new subvariant and (iii) improving developability characteristics of antibodies while retaining binding properties. These results together demonstrate an end-to-end antibody design pipeline with applicability across a wide range of antibody design tasks. We experimentally characterized binding against different antigen targets, developability profiles, and cryo-EM structures of designed antibodies. Our work demonstrates how combined AI and physics computational methods improve productivity and viability of antibody designs

Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study

Background: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. Methods: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4–5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4–9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. Findings: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9–63·9], p<0·001) or MACE (12·6 [8·5–18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17–8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93–5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. Interpretation: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators

MscS-like mechanosensitive channels in plants and microbes

The challenge of osmotic stress is something all living organisms must face as a result of environmental dynamics. Over the past three decades, innovative research and cooperation across disciplines have irrefutably established that cells utilize mechanically gated ion channels to release osmolytes and prevent cell lysis during hypoosmotic stress. Early electrophysiological analysis of the inner membrane of Escherichia coli identified the presence of three distinct mechanosensitive activities. The subsequent discoveries of the genes responsible for two of these activities, the mechanosensitive channels of large (MscL) and small (MscS) conductance, led to the identification of two diverse families of mechanosensitive channels. The latter of these two families, the MscS family, consists of members from bacteria, archaea, fungi, and plants. Genetic and electrophysiological analysis of these family members has provided insight into how organisms use mechanosensitive channels for osmotic regulation in response to changing environmental and developmental circumstances. Furthermore, determining the crystal structure of E. coli MscS and several homologues in several conformational states has contributed to our understanding of the gating mechanisms of these channels. Here we summarize our current knowledge of MscS homologues from all three domains of life and address their structure, proposed physiological functions, electrophysiological behaviors, and topological diversity