Equine-assisted service's effect on cartilage and skeletal biomarkers for adults and older adults with arthritis: A pilot study.

OBJECTIVE: The object of this study was to determine the effect of EAS (Equine-Assisted Services) on arthritis conditions, as measured by the sTnT (Skeletal troponin) and COMP (cartilage oligomeric matrix proteins) biomarkers, compared to an exercise attention control intervention. DESIGN: This was a secondary analysis of a randomized clinical trial comparing equine-assisted therapy to exercise education attention-control on cartilage and skeletal biomarkers in adults with arthritis. Twenty-one adults (Mage = 64 years) with arthritis who attended rheumatology clinics in the midwestern United States participated. RESULTS: No changes were found in sTnT from baseline to week six within either intervention nor were there differences in changes between the two groups (p = 0.91). COMP increased from baseline to week six for both conditions, suggesting increased deterioration of cartilage and joints. Although the attention-control condition demonstrated larger increases in cartilage oligomeric matrix proteins level, compared to the EAS condition, these differences were not statistically (p = 0.58) or clinically significant (i.e., trivial effect, d = -0.16). When 3 outliers were removed, the differences in changes between EAT and attention-control group could be arguably of clinical significance (d = - 0.33), suggesting that the attention-control group demonstrated larger increases in levels of COMP than those in the EAS condition, though this difference was not statistically significant (p = 0.28). CONCLUSION: Although equine-assisted therapy may reduce pain and improve quality of life for adults with arthritis, findings here are not fully corroborated with biomarkers.

Performance of the beta-glucan test for the diagnosis of invasive fusariosis and scedosporiosis: a meta-analysis.

The (1→3)-ß-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold infections (IMI) in patients with hematologic cancer or other immunosuppressive conditions. However, its use is limited by modest sensitivity/specificity, inability to differentiate between fungal pathogens, and lack of detection of mucormycosis. Data about BDG performance for other relevant IMI, such as invasive fusariosis (IF) and invasive scedosporiosis/lomentosporiosis (IS) are scarce. The objective of this study was to assess the sensitivity of BDG for the diagnosis of IF and IS through systematic literature review and meta-analysis. Immunosuppressed patients diagnosed with proven or probable IF and IS, with interpretable BDG data were eligible. A total of 73 IF and 27 IS cases were included. The sensitivity of BDG for IF and IS diagnosis was 76.7% and 81.5%, respectively. In comparison, the sensitivity of serum galactomannan for IF was 27%. Importantly, BDG positivity preceded the diagnosis by conventional methods (culture or histopathology) in 73% and 94% of IF and IS cases, respectively. Specificity was not assessed because of lacking data. In conclusion, BDG testing may be useful in patients with suspected IF or IS. Combining BDG and galactomannan testing may also help differentiating between the different types of IMI.

IF and IS are severe fungal infections for which diagnosis is often delayed. This meta-analysis shows that beta-glucan testing in serum had a sensitivity of about 80% for IF/IS and could detect the disease earlier compared to conventional diagnostic tests.

The Presence of Two MyoD Genes in a Subset of Acanthopterygii Fish Is Associated with a Polyserine Insert in MyoD1.

The MyoD gene was duplicated during the teleost whole genome duplication and, while a second MyoD gene (MyoD2) was subsequently lost from the genomes of some lineages (including zebrafish), many fish lineages (including Alcolapia species) have retained both MyoD paralogues. Here we reveal the expression patterns of the two MyoD genes in Oreochromis (Alcolapia) alcalica using in situ hybridisation. We report our analysis of MyoD1 and MyoD2 protein sequences from 54 teleost species, and show that O. alcalica, along with some other teleosts, include a polyserine repeat between the amino terminal transactivation domains (TAD) and the cysteine-histidine rich region (H/C) in MyoD1. The evolutionary history of MyoD1 and MyoD2 is compared to the presence of this polyserine region using phylogenetics, and its functional relevance is tested using overexpression in a heterologous system to investigate subcellular localisation, stability, and activity of MyoD proteins that include and do not include the polyserine region.

Frequency of Medication Administration Timing Error in Hospitals: A Systematic Review.

BACKGROUND: Medication administration timing error (MATE) leads to poor medication efficacy, harm, and death. Frequency of MATE is understudied. PURPOSE: To determine MATE frequency, and characteristics and quality of reporting studies. METHODS: A systematic review of articles between 1999 and 2021 was conducted using the Cumulative Index of Nursing and Allied Health Literature, ProQuest, and PubMed databases. Articles were scored for quality using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. RESULTS: Initially, 494 articles were screened; 23 were included in this review. MATE was defined as administration beyond 60 minutes before or after the scheduled time in 13 (57%) of the included studies. Measurement procedures included data abstraction, self-report, and observation. Frequency of MATE was 1% to 72.6%. Moderate study quality was found in 78% of articles. CONCLUSION: Research on MATE is characterized by inconsistent definitions, measurements procedures, and calculation techniques. High-quality studies are lacking. Many research improvement opportunities exist.

Two closely related ureotelic fish species of the genus Alcolapia express different levels of ammonium transporters in gills.

Most fish excrete their nitrogenous waste across the gills as ammonia through the activity of the Rhesus glycoprotein ammonium transporters. In contrast, fish of the subgenus Alcolapia (Oreochromis) are the only vertebrates that survive the extreme conditions of the soda lakes of Natron and Magadi in East Africa and have evolved adaptations to the highly alkaline waters including the ability to excrete their nitrogenous waste as urea. Nevertheless, Alcolapia retain the Rhesus glycoprotein genes in their genomes and using two heterologous expression systems, we demonstrate that Alcolapia Rhbg is capable of moving ammonia. Comparing ammonia and urea excretion from two closely related Alcolapia species from the same aquarium, we found that while Alcolapia grahami remains fully ureotelic after many generations in lab conditions, Alcolapia alcalica excretes some of its nitrogenous waste as ammonia. Using in situ hybridisation, we demonstrate robust, localised gene expression of Rhbg, rhcg1 and rhcg2 in the gill tissue in both A. alcalica embryos and adults, similar to that in other ammoniotelic fish. In contrast, the expression of these genes in A. grahami gills is much lower than in A. alcalica, suggesting the rapid evolution of a molecular mechanism underlying the complete ureotelism of A. grahami.

The Effect of Immersive Training on Emergency Preparedness for Interdisciplinary College Students: A Single Group Pretest, Posttest.

OBJECTIVE: Current standard practice for disaster response training is insufficient to prepare future responders. Interdisciplinary immersive education is necessary for disaster responders to react quickly to the devastating destruction, dangerous situations, and ethical dilemmas, while caring for survivors, families, and communities with limited resources. This study tests the effects of immersive emergency preparedness education on interdisciplinary college students. METHODS: Thirty-four college students attended a 3-day immersive disaster training event. Interdisciplinary teams were given 6 challenges to adapt and overcome: mass casualty; field hospital triage, treatment, and transportation; water rescue; high building rescue; search and rescue; and a water treatment. A pretest and posttest survey, Emergency Preparedness Information Questionnaire (EPIQ), was administered to all participants. RESULTS: Statistically significant improvements in triage, biological agent detection, assessing critical resources, incident command, psychological issues, clinical decision making, and communication (range of P = 0.000-0.003). Improvement in clinical significance resulted in a change from limited knowledge to familiarity with the subject in all cases except isolation, quarantine, and decontamination. CONCLUSIONS: Preparation and training of health care professionals need to include immersive disaster scenarios that create the experience of fatigue, psychological challenges, and physical stresses.

"Moving the Science Forward": Faculty Perceptions of Culturally Diverse Mentor Training Benefits, Challenges, and Support.

There is a pressing need for deeper cultural awareness among postsecondary faculty, yet few studies focus on institutions with developing research infrastructure, which enroll large proportions of racially minoritized students. Using social exchange theory, we investigate faculty members' perceptions of "culturally diverse mentor training," which includes culturally aware mentor (CAM) training, Entering Mentoring, and self-designed mentor training initiatives. Data come from qualitative interviews with 74 faculty who participated in culturally diverse mentor training activities across 10 master's and doctoral institutions in the early stages of implementing grant-funded interventions focused on determining the most effective ways to engage and retain racially minoritized students in biomedical research. Findings indicate that faculty perceived a deepened understanding of their mentees' challenges and developed enhanced communication strategies to better appreciate cultural differences. Faculty reported several challenges, such as difficulty in adopting culturally sustaining practices, balancing multiple commitments internal and external of grant requirements, and dissatisfaction with facilitators from outside their disciplines. They also described supportive structures that decreased their mentoring workload, such as complementary curricula and tiered mentoring models. We conclude with implications for higher education leaders interested in adapting and scaling culturally diverse mentor training interventions within their own departments and institutions.

Implementing case study design to evaluate diverse institutions and STEM education contexts: Lessons and key areas for systematic study.

This chapter highlights the important contributions of case study research to the evaluation of student-centered programs and broader STEM initiatives in higher education. We summarize the Diversity Program Consortium's case study evaluation of the Building Infrastructure Leading to Diversity (BUILD) initiative, funded by the National Institutes of Health (NIH), with aims to enhance diversity in the NIH-funded workforce. We describe lessons learned from the case study design used for the evaluation of BUILD that applies to administrators of STEM initiatives who are interested in case study methods and to evaluators who are familiar with case studies and tasked with program evaluation of a multisite STEM program. These lessons include practical considerations for logistics and the importance of clarifying the goals of the case study design within the larger program evaluation, fostering the continuation of knowledge within the evaluation team, and embedding trust building and collaboration throughout all stages of the case study.

Improved Knowledge of Disaster Preparedness in Underrepresented Secondary Students: A Quasi-Experimental Study.

BACKGROUND: Disasters cause significant human and monetary destruction and society as a whole is underprepared to address them. Disaster preparedness education is not covered extensively enough for health professionals or for the general public. METHODS: A disaster preparedness education intervention was performed using a non-randomized controlled trial of a convenience sample with a pre- and post-intervention survey. The adapted Emergency Preparedness Information Questionnaire (EPIQ), a validated survey tool, was utilized. Participants came from a health professions educational enrichment program for students from under-resourced high schools in the Kansas City area. RESULTS: The experimental group shows statistically significant improvement in knowledge of disaster topics post-intervention. Of 18 adapted EPIQ tool questions, 17 show statistically significant improvement in disaster knowledge post-intervention for the experimental group with significance set at p < .05 (range of significant p values .000-.017). CONCLUSIONS: The education intervention was effective and cost-efficient. Disaster preparedness education should be included in THE secondary school curriculum.

Recent Advances and Novel Approaches in Laboratory-Based Diagnostic Mycology.

What was once just culture and microscopy the field of diagnostic mycology has significantly advanced in recent years and continues to incorporate novel assays and strategies to meet the changes in clinical demand. The emergence of widespread resistance to antifungal therapy has led to the development of a range of molecular tests that target mutations associated with phenotypic resistance, to complement classical susceptibility testing and initial applications of next-generation sequencing are being described. Lateral flow assays provide rapid results, with simplicity allowing the test to be performed outside specialist centres, potentially as point-of-care tests. Mycology has responded positively to an ever-diversifying patient population by rapidly identifying risk and developing diagnostic strategies to improve patient management. Nowadays, the diagnostic repertoire of the mycology laboratory employs classical, molecular and serological tests and should be keen to embrace diagnostic advancements that can improve diagnosis in this notoriously difficult field.

Adaptation of the carbamoyl-phosphate synthetase enzyme in an extremophile fish.

Tetrapods and fish have adapted distinct carbamoyl-phosphate synthase (CPS) enzymes to initiate the ornithine urea cycle during the detoxification of nitrogenous wastes. We report evidence that in the ureotelic subgenus of extremophile fish Oreochromis Alcolapia, CPS III has undergone convergent evolution and adapted its substrate affinity to ammonia, which is typical of terrestrial vertebrate CPS I. Unusually, unlike in other vertebrates, the expression of CPS III in Alcolapia is localized to the skeletal muscle and is activated in the myogenic lineage during early embryonic development with expression remaining in mature fish. We propose that adaptation in Alcolapia included both convergent evolution of CPS function to that of terrestrial vertebrates, as well as changes in development mechanisms redirecting CPS III gene expression to the skeletal muscle.

Exploring the Expression of Cardiac Regulators in a Vertebrate Extremophile: The Cichlid Fish Oreochromis (Alcolapia) alcalica.

Although it is widely accepted that the cellular and molecular mechanisms of vertebrate cardiac development are evolutionarily conserved, this is on the basis of data from only a few model organisms suited to laboratory studies. Here, we investigate gene expression during cardiac development in the extremophile, non-model fish species, Oreochromis (Alcolapia) alcalica. We first characterise the early development of O. alcalica and observe extensive vascularisation across the yolk prior to hatching. We further investigate heart development by identifying and cloning O. alcalica orthologues of conserved cardiac transcription factors gata4, tbx5, and mef2c for analysis by in situ hybridisation. Expression of these three key cardiac developmental regulators also reveals other aspects of O. alcalica development, as these genes are expressed in developing blood, limb, eyes, and muscle, as well as the heart. Our data support the notion that O. alcalica is a direct-developing vertebrate that shares the highly conserved molecular regulation of the vertebrate body plan. However, the expression of gata4 in O. alcalica reveals interesting differences in the development of the circulatory system distinct from that of the well-studied zebrafish. Understanding the development of O. alcalica embryos is an important step towards providing a model for future research into the adaptation to extreme conditions; this is particularly relevant given that anthropogenic-driven climate change will likely result in more freshwater organisms being exposed to less favourable conditions.

Equine-assisted therapies using horses as healers: A concept analysis.

Aims: A concept analysis was conducted to clarify the attributes, antecedents and meaning of equine-assisted therapy and present an operational definition. Design: Concept analysis. Methods: Walker and Avant's concept analysis method was used to analyse equine-assisted therapy, using horses as healers by defining and enumerating the attributes, antecedents, consequences and empirical referents. Example cases are presented. Results: Defining attributes include the following: a human participant with an equine physically present to assist the human participant, a treatment or intervention as a result of the interactions between an equine and a human participant, a purposeful and regulated interaction and a positive health outcome goal from the interaction. Antecedents include a live horse with a human physically able to interact with the horse, a facilitator and accessibility to an equine-assisted therapy (EAT) programme. Consequences include improved balance, well-being, quality of life, trust, spasticity, self-efficacy, self-esteem, nurse presence, pleasure and a sense of accomplishment.

An equine-assisted therapy intervention to improve pain, range of motion, and quality of life in adults and older adults with arthritis: A randomized controlled trial.

RESEARCH AIM: To compare equine-assisted therapy to exercise education on pain, range of motion, and quality of life in adults and older adults with arthritis. BACKGROUND: Quality of life for adults and older adults is negatively impacted by arthritis pain, stiffness, and decreased function. Equine-assisted therapy provides unique movements to the rider's joints and muscles improving pain, range of motion, and quality of life and has improved outcomes in balance, gait, strength, functional mobility, and spasticity for older adults, stroke, spinal cord injury, and multiple sclerosis patients. No research has investigated the effects on adults and older adults with arthritis. METHODS: Twenty adults and older adults with arthritis recruited from rheumatology clinics participated in a randomized controlled trial for six weeks. Participants and research assistants were blinded to assignment. Standardized valid and reliable instruments were used to measure pain, range of motion, and quality of life targeting back, knees, shoulders, and hips. RESULTS: Mean age was 63.85 (SD 6.885, 53-75) years. Pain significantly improved in shoulders (p = 0.007), hips (p = 0.027), and back (p = 0.006), not knees (p = 0.061). Range of motion improved for back (p = 0.02), hips (p = 0.04), shoulders (p = 0.005) and not knees. Quality of life improved for upper limb (p = 0.002), lower limb (p = 0.021), and affect (p = 0.030), not social interaction and symptoms. CONCLUSION: This randomized controlled trial provides evidence that equine-assisted therapy decreases pain, and improves range of motion, and quality of life for adults and older adults with arthritis. Further fully powered research with cost/benefit outcomes would be beneficial.

Polymerase chain reaction blood tests for the diagnosis of invasive aspergillosis in immunocompromised people.

BACKGROUND: This is an update of the original review published in the Cochrane Database of Systematic Reviews Issue 10, 2015.Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mould infection in immunocompromised people. Early diagnosis of IA and prompt administration of appropriate antifungal treatment are critical to the survival of people with IA. Antifungal drugs can be given as prophylaxis or empirical therapy, instigated on the basis of a diagnostic strategy (the pre-emptive approach) or for treating established disease. Consequently, there is an urgent need for research into both new diagnostic tools and drug treatment strategies. Increasingly, newer methods such as polymerase chain reaction (PCR) to detect fungal nucleic acids are being investigated. OBJECTIVES: To provide an overall summary of the diagnostic accuracy of PCR-based tests on blood specimens for the diagnosis of IA in immunocompromised people. SEARCH METHODS: We searched MEDLINE (1946 to June 2015) and Embase (1980 to June 2015). We also searched LILACS, DARE, Health Technology Assessment, Web of Science and Scopus to June 2015. We checked the reference lists of all the studies identified by the above methods and contacted relevant authors and researchers in the field. For this review update we updated electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3) in the Cochrane Library; MEDLINE via Ovid (June 2015 to March week 2 2018); and Embase via Ovid (June 2015 to 2018 week 12). SELECTION CRITERIA: We included studies that: i) compared the results of blood PCR tests with the reference standard published by the European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG); ii) reported data on false-positive, true-positive, false-negative and true-negative results of the diagnostic tests under investigation separately; and iii) evaluated the test(s) prospectively in cohorts of people from a relevant clinical population, defined as a group of individuals at high risk for invasive aspergillosis. Case-control and retrospective studies were excluded from the analysis. DATA COLLECTION AND ANALYSIS: Authors independently assessed quality and extracted data. For PCR assays, we evaluated the requirement for either one or two consecutive samples to be positive for diagnostic accuracy. We investigated heterogeneity by subgroup analyses. We plotted estimates of sensitivity and specificity from each study in receiver operating characteristics (ROC) space and constructed forest plots for visual examination of variation in test accuracy. We performed meta-analyses using the bivariate model to produce summary estimates of sensitivity and specificity. MAIN RESULTS: We included 29 primary studies (18 from the original review and 11 from this update), corresponding to 34 data sets, published between 2000 and 2018 in the meta-analyses, with a mean prevalence of proven or probable IA of 16.3 (median prevalence 11.1% , range 2.5% to 57.1%). Most patients had received chemotherapy for haematological malignancy or had undergone hematopoietic stem cell transplantation. Several PCR techniques were used among the included studies. The sensitivity and specificity of PCR for the diagnosis of IA varied according to the interpretative criteria used to define a test as positive. The summary estimates of sensitivity and specificity were 79.2% (95% confidence interval (CI) 71.0 to 85.5) and 79.6% (95% CI 69.9 to 86.6) for a single positive test result, and 59.6% (95% CI 40.7 to 76.0) and 95.1% (95% CI 87.0 to 98.2) for two consecutive positive test results. AUTHORS' CONCLUSIONS: PCR shows moderate diagnostic accuracy when used as screening tests for IA in high-risk patient groups. Importantly the sensitivity of the test confers a high negative predictive value (NPV) such that a negative test allows the diagnosis to be excluded. Consecutive positives show good specificity in diagnosis of IA and could be used to trigger radiological and other investigations or for pre-emptive therapy in the absence of specific radiological signs when the clinical suspicion of infection is high. When a single PCR positive test is used as the diagnostic criterion for IA in a population of 100 people with a disease prevalence of 16.3% (overall mean prevalence), three people with IA would be missed (sensitivity 79.2%, 20.8% false negatives), and 17 people would be unnecessarily treated or referred for further tests (specificity of 79.6%, 21.4% false positives). If we use the two positive test requirement in a population with the same disease prevalence, it would mean that nine IA people would be missed (sensitivity 59.6%, 40.4% false negatives) and four people would be unnecessarily treated or referred for further tests (specificity of 95.1%, 4.9% false positives). Like galactomannan, PCR has good NPV for excluding disease, but the low prevalence of disease limits the ability to rule in a diagnosis. As these biomarkers detect different markers of disease, combining them is likely to prove more useful.

Molecular community profiling of the bacterial microbiota associated with denture-related stomatitis.

Denture-associated stomatitis (DS) affects over two-thirds of denture-wearers. DS presents as erythema of the palatal mucosa in areas where denture-surface associated polymicrobial biofilms containing the fungus Candida albicans exist. The contribution of the oral bacterial microbiota toward the infection is unknown. Therefore, this study characterised the bacterial microbiota of sites within the oral cavity to identify potential associations with occurrence of DS. Denture-wearing patients were recruited (denture stomatitis (DS) n = 8; non-denture stomatitis (NoDS) n = 11) and the oral bacterial microbiota of the tongue, palate and denture-fitting surface was characterised using next-generation sequencing. Operational taxonomic units (OTUs) were identified to bacterial genera and species, and presence/absence and relative abundances were examined. A significant (P = 0.007) decrease in the number of OTUs and thus, diversity of the microbiota was observed in tongue samples of DS patients (vs non-DS). The microbiota of denture-fitting surfaces and palatal mucosae were similar. Large differences in the abundance of bacterial genera and species were observed at each sample site, and unique presence/absence of bacteria was noted. Presence/absence and relative abundance of specific bacteria associated with DS warrants further in vitro and in vivo evaluation, particularly as our previous work has shown C. albicans virulence factor modulation by oral bacteria.

The effect of gut microbiota elimination in Drosophila melanogaster: A how-to guide for host-microbiota studies.

In recent years, there has been a surge in interest in the effects of the microbiota on the host. Increasingly, we are coming to understand the importance of the gut microbiota in modulating host physiology, ecology, behavior, and evolution. One method utilized to evaluate the effect of the microbiota is to suppress or eliminate it, and compare the effect on the host with that of untreated individuals. In this study, we evaluate some of these commonly used methods in the model organism, Drosophila melanogaster. We test the efficacy of a low-dose streptomycin diet, egg dechorionation, and an axenic or sterile diet, in the removal of gut bacteria within this species in a fully factorial design. We further determine potential side effects of these methods on host physiology by performing a series of standard physiological assays. Our results showed that individuals from all treatments took significantly longer to develop, and weighed less, compared to normal flies. Males and females that had undergone egg dechorionation weighed significantly less than streptomycin reared individuals. Similarly, axenic female flies, but not males, were much less active when analyzed in a locomotion assay. All methods decreased the egg to adult survival, with egg dechorionation inducing significantly higher mortality. We conclude that low-dose streptomycin added to the dietary media is more effective at removing the gut bacteria than egg dechorionation and has somewhat less detrimental effects to host physiology. More importantly, this method is the most practical and reliable for use in behavioral research. Our study raises the important issue that the efficacy of and impacts on the host of these methods require investigation in a case-by-case manner, rather than assuming homogeneity across species and laboratories.

Diversity of Pneumocystis jirovecii Across Europe: A Multicentre Observational Study.

Pneumocystis jirovecii is an airborne human-specific ascomycetous fungus responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients, affecting >500,000 patients per year (www.gaffi.org). The understanding of its epidemiology is limited by the lack of standardised culture. Recent genotyping data suggests a limited genetic diversity of P. jirovecii. The objective of the study was to assess the diversity of P. jirovecii across European hospitals and analyse P. jirovecii diversity in respect to clinical data obtained from the patients. Genotyping was performed using six already validated short tandem repeat (STR) markers on 249 samples (median: 17 per centre interquartile range [11-20]) from PCP patients of 16 European centres. Mixtures of STR markers (i.e., ≥2 alleles for ≥1 locus) were detected in 67.6% (interquartile range [61.4; 76.5]) of the samples. Mixture was significantly associated with the underlying disease of the patient, with an increased proportion in HIV patients (78.3%) and a decreased proportion in renal transplant recipients (33.3%) (p<0.001). The distribution of the alleles was significantly different (p<0.001) according to the centres in three out of six markers. In analysable samples, 201 combinations were observed corresponding to 137 genotypes: 116 genotypes were country-specific; 12 in two; six in three; and two in four and one in five countries. Nine genotypes were recorded more than once in a given country. Genotype 123 (Gt123) was significantly associated with France (14/15, p<0.001) and Gt16 with Belgium (5/5, p<0.001). More specifically, Gt123 was observed mainly in France (14/15/16 patients) and in renal transplant patient (13/15). Our study showed the wide population diversity across Europe, with evidence of local clusters of patients harbouring a given genotype. These data suggest a specific association between genotype and underlying disease, with evidence of a different natural history of PCP in HIV patients and renal transplant recipients.