An improved method for determining codon variability in a gene and its application to the rate of fixation of mutations in evolution

If one has the amino acid sequences of a set of homologous proteins as well as their phylogenetic relationships, one can easily determine the minimum number of mutations (nucleotide replacements) which must have been fixed in each codon since their common ancestor. It is found that for 29 species of cytochrome c the data fit the assumption that there is a group of approximately 32 invariant codons and that the remainder compose two Poisson-distributed groups of size 65 and 16 codons, the latter smaller group fixing mutations at about 3.2 times the rate of the larger. It is further found that the size of the invariant group increases as the range of species is narrowed. Extrapolation suggests that less than 10% of the codons in a given mammalian cytochrome c gene are capable of accepting a mutation. This is consistent with the view that at any one point in time only a very restricted number of positions can fix mutations but that as mutations are fixed the positions capable of accepting mutations also change so that examination of a wide range of species reveals a wide range of altered positions. We define this restricted group as the concomitantly variable codons. Given this restriction, the fixation rates for mutations in concomitantly variable codons in cytochrome c and fibrinopeptide A are not very different, a result which should be the case if most of these mutations are in fact selectively neutral as Kimura suggests.Paper number 1382 from the Laboratory of Genetics. Work performed in part at the University of Iowa, Department of Preventive Medicine and Environmental Health and Department of Statistics, Iowa City, Iowa. Computing supported by the Graduate College, University of Iowa.     

Interpersonal psychotherapy delivered by nonspecialists for depression and posttraumatic stress disorder among Kenyan HIV–positive women affected by gender-based violence: Randomized controlled trial

BackgroundHIV–positive women suffer a high burden of mental disorders due in part to gender-based violence (GBV). Comorbid depression and posttraumatic stress disorder (PTSD) are typical psychiatric consequences of GBV. Despite attention to the HIV-GBV syndemic, few HIV clinics offer formal mental healthcare. This problem is acute in sub-Saharan Africa, where the world’s majority of HIV–positive women live and prevalence of GBV is high.Methods and findingsWe conducted a randomized controlled trial at an HIV clinic in Kisumu, Kenya. GBV-affected HIV–positive women with both major depressive disorder (MDD) and PTSD were randomized to 12 sessions of interpersonal psychotherapy (IPT) plus treatment as usual (TAU) or Wait List+TAU. Nonspecialists were trained to deliver IPT inside the clinic. After 3 months, participants were reassessed, and those assigned to Wait List+TAU were given IPT. The primary outcomes were diagnosis of MDD and PTSD (Mini International Neuropsychiatric Interview) at 3 months. Secondary outcomes included symptom measures of depression and PTSD, intimate partner violence (IPV), and disability. A total of 256 participants enrolled between May 2015 and July 2016. At baseline, the mean age of the women in this study was 37 years; 61% reported physical IPV in the past week; 91% reported 2 or more lifetime traumatic events and monthly income was 18USD. Multilevel mixed-effects logistic regression showed that participants randomized to IPT+TAU had lower odds of MDD (odds ratio [OR] 0.26, 95% CI [0.11 to 0.60], p = 0.002) and lower odds of PTSD (OR 0.35, [0.14 to 0.86], p = 0.02) than controls. IPT+TAU participants had lower odds of MDD-PTSD comorbidity than controls (OR 0.36, 95% CI [0.15 to 0.90], p = 0.03). Linear mixed models were used to assess secondary outcomes: IPT+TAU participants had reduced disability (−6.9 [−12.2, −1.5], p = 0.01), and nonsignificantly reduced work absenteeism (−3.35 [−6.83, 0.14], p = 0.06); partnered IPT+TAU participants had a reduction of IPV (−2.79 [−5.42, −0.16], p = 0.04). Gains were maintained across 6-month follow-up. Treatment group differences were observed only at month 3, the time point at which the groups differed in IPT status (before cross over). Study limitations included 35% attrition inclusive of follow-up assessments, generalizability to populations not in HIV care, and data not collected on TAU resources accessed.ConclusionsIPT for MDD and PTSD delivered by nonspecialists in the context of HIV care yielded significant improvements in HIV–positive women’s mental health, functioning, and GBV (IPV) exposure, compared to controls.Trial registrationClinical Trials Identifier {"type":"clinical-trial","attrs":{"text":"NCT02320799","term_id":"NCT02320799"}}NCT02320799.

Susan Meffert and co-workers evaluate interpersonal psychotherapy for treatment of psychiatric disorders in women with HIV infection in Kenya.     

Radiologic assessment in the pediatric intensive care unit.

The severely ill infant or child who requires admission to a pediatric intensive care unit (PICU) often presents with a complex set of problems necessitating multiple and frequent management decisions. Diagnostic imaging plays an important role, not only in the initial assessment of the patient''s condition and establishing a diagnosis, but also in monitoring the patient''s progress and the effects of interventional therapeutic measures. Bedside studies obtained using portable equipment are often limited but can provide much useful information when a careful and detailed approach is utilized in producing the radiograph and interpreting the examination. This article reviews some of the basic principles of radiographic interpretation and details some of the diagnostic points which, when promptly recognized, can lead to a better understanding of the patient''s condition and thus to improved patient care and management. While chest radiography is stressed, studies of other regions including the upper airway, abdomen, skull, and extremities are discussed. A brief consideration of the expanding role of new modality imaging (i.e., ultrasound, CT) is also included. Multiple illustrative examples of common and uncommon problems are shown.     

SKIN SWABBING FOR GENETIC ANALYSIS: APPLICATION TO DUSKY DOLPHINS (LAGENORHYNCHUS OBSCURUS)

Exfoliated skin was collected from bowriding dolphins with the use of a sterilized nylon scrub pad affixed to a wooden dowel. Initial tests of the effectiveness of the technique and dolphin behavioral responses were conducted on dusky dolphins off Kaikoura, New Zealand. During 14 sampling days, 128 contacts using this procedure were made with bowriding dolphins, of which 114 showed behavioral response. Responses during sampling were mild, with 11% of contacted individuals showing no visible response, and 66% of individuals which could be monitored for 30 sec after contact returning to bowride within 30 sec. Mean return time was 10 sec postcontact and did not vary significantly for groups of different sizes. Behavioral controls suggest that a proportion of responses could be explained by typical dolphin behavior in the presence of boats. Seventy-eight percent of contacts resulted in successful collection of tissue samples. Sample time was three minutes on average. Size of group and behavioral state did not appear to influence sample time. Preliminary genetic analyses revealed that tissue collected by this technique was suitable for amplification and sequencing of mitochondrial DNA (mtDNA) via PCR. Comparisons of mtDNA control region sequences with those from known L. obscurus and other delphinid samples verified that this technique was robust against contamination from elements in sea water.