Dramatic intraspecific natural variation in photosynthetic responses to cold is controlled mainly by a few large effect QTLs, and some cold-responsive photosynthesis QTLs may contribute to local ...adaptation.
Abstract
Local adaptation is common, but the traits and genes involved are often unknown. Physiological responses to cold probably contribute to local adaptation in wide-ranging species, but the genetic basis underlying natural variation in these traits has rarely been studied. Using a recombinant inbred (495 lines) mapping population from locally adapted populations of Arabidopsis thaliana from Sweden and Italy, we grew plants at low temperature and mapped quantitative trait loci (QTLs) for traits related to photosynthesis: maximal quantum efficiency (Fv/Fm), rapidly reversible photoprotection (NPQfast), and photoinhibition of PSII (NPQslow) using high-throughput, whole-plant measures of chlorophyll fluorescence. In response to cold, the Swedish line had greater values for all traits, and for every trait, large effect QTLs contributed to parental differences. We found one major QTL affecting all traits, as well as unique major QTLs for each trait. Six trait QTLs overlapped with previously published locally adaptive QTLs based on fitness measured in the native environments over 3 years. Our results demonstrate that photosynthetic responses to cold can vary dramatically within a species, and may predominantly be caused by a few QTLs of large effect. Some photosynthesis traits and QTLs probably contribute to local adaptation in this system.
Summary
Background
People with Diabetes Mellitus (DM) are at increased risk of postoperative complications if their HbA1C readings are not well controlled. In the UK, there are clear national ...guidelines requiring all people with DM to have HbA1C blood testing within 6months before undergoing surgery and that these readings should be below 69 mmol/mol if this is safe to achieve. The aim of this study was to determine whether hospitals in the region were compliant with the guidelines.
Methods
Data were prospectively collected from seven hospitals across the East of England region from 1st October 2017 to 31st March 2018 (6 months) in all people with DM undergoing elective day case procedures in General and Vascular surgery for benign disease.
Results
A total of 181 people with DM were included in the study, of whom 77.9% were male patients and the median age was 63 years. The three most commonly performed operations were laparoscopic cholecystectomy (20.9%, n = 38/181), inguinal hernia repair (20.4%, n = 37/181) and umbilical/para‐umbilical hernia repair (11.0%, n = 20/181). In keeping with the national guidelines, only 86.7% (n = 157/181) of patients had an HbA1C tested within 6 months prior to their surgery date. Of the patients who had a preoperative HbA1C, 14 (n = 14/157, 8.9%) had an HbA1C ≥ 69 mmol/mol, and 12 (n = 12/14, 85.7%) of these proceeded to surgery without optimisation of their HbA1C.
Conclusion
A significant proportion of people with diabetes undergoing elective day case procedures in our region do not have HbA1C testing within 6 months of their procedure as recommended by the national guidelines. In patients who do have a high HbA1C, the majority still undergo surgery without adequate control of their DM. Greater awareness amongst healthcare workers and robust pathways are required for this vulnerable group of patients if we are to reduce the risk of developing postoperative complication rates.
HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to ...second-line ART in sub-Saharan Africa.
We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.
Of 297,825 eligible patients, 10,352 (3%) switched to second-line ART during 782 ,412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine viral load monitoring, 1·21 (1·13-1·30) for targeted viral load monitoring, and 0·49 (0·43-0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5-59·6) switched by 2 years, and of 15,892 patients with confirmed immunological failure, 19·3% (18·5-20·0) switched by 2 years. Of 10,352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per μL).
Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.
National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.
Local adaptation is common, but the traits and genes involved are often unknown. Physiological responses to cold probably contribute to local adaptation in wide-ranging species, but the genetic basis ...underlying natural variation in these traits has rarely been studied. Using a recombinant inbred (495 lines) mapping population from locally adapted populations of Arabidopsis thaliana from Sweden and Italy, we grew plants at low temperature and mapped quantitative trait loci (QTLs) for traits related to photosynthesis: maximal quantum efficiency (Fv/Fm), rapidly reversible photoprotection (NPQfast), and photoinhibition of PSII (NPQslow) using high-throughput, whole-plant measures of chlorophyll fluorescence. In response to cold, the Swedish line had greater values for all traits, and for every trait, large effect QTLs contributed to parental differences. We found one major QTL affecting all traits, as well as unique major QTLs for each trait. Six trait QTLs overlapped with previously published locally adaptive QTLs based on fitness measured in the native environments over 3 years. Our results demonstrate that photosynthetic responses to cold can vary dramatically within a species, and may predominantly be caused by a few QTLs of large effect. Some photosynthesis traits and QTLs probably contribute to local adaptation in this system.
Introduction
Adolescence and pregnancy are potential risk factors for loss to follow‐up (LTFU) while on antiretroviral therapy (ART). We compared adolescent and adult LTFU after ART initiation to ...quantify the impact of age, pregnancy, and site‐level factors on LTFU.
Methods
We used routine clinical data for patients initiating ART as young adolescents (YA; 10 to 14 years), older adolescents (OA; 15 to 19 years) and adults (≥20 years) from 2000 to 2014 at 52 health facilities affiliated with the International epidemiology Databases to Evaluate AIDS (IeDEA) East Africa collaboration. We estimated cumulative incidence (95% confidence interval, CI) of LTFU (no clinic visit for ≥6 months after ART initiation) and identified patient and site‐level correlates of LTFU, using multivariable Cox proportional hazards models for all patients as well as individual age groups.
Results
A total of 138,387 patients initiated ART, including 2496 YA, 2955 OA and 132,936 adults. Of these, 55%, 78% and 66%, respectively, were female and 0.7% of YA, 22.3% of OA and 8.3% of adults were pregnant at ART initiation. Cumulative incidence of LTFU at five years was 26.6% (24.6 to 28.6) among YA, 44.1% (41.8 to 46.3) among OA and 29.3% (29.1 to 29.6) among adults. Overall, compared to adults, the adjusted hazard ratio, aHR, (95% CI) of LTFU for OA was 1.54 (1.41 to 1.68) and 0.77 (0.69 to 0.86) for YA. Compared to males, pregnant females had higher hazard of LTFU, aHR 1.20 (1.14 to 1.27), and nonpregnant women had lower hazard aHR 0.90 (0.88 to 0.93). LTFU hazard among the OA was primarily driven by both pregnant and nonpregnant females, aHR 2.42 (1.98 to 2.95) and 1.51 (1.27 to 1.80), respectively, compared to men. The LTFU hazard ratio varied by IeDEA program. Site‐level factors associated with overall lower LTFU hazard included receiving care in tertiary versus primary‐care clinics aHR 0.61 (0.56 to 0.67), integrated adult and adolescent services and food ration provision aHR 0.93 (0.89 to 0.97) versus nonintegrated clinics with food ration provision, having patient support groups aHR 0.77 (0.66 to 0.90) and group adherence counselling aHR 0.61 (0.57 to 0.67).
Conclusions
Older adolescents experienced higher risk of LTFU compared to YA and adults. Interventions to prevent LTFU among older adolescents are critically needed, particularly for female and/or pregnant adolescents.
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