Interdisciplinary syntheses are needed to scale up discovery of the environmental drivers and molecular basis of adaptation in nature. Here we integrated novel approaches using whole genome ...sequences, satellite remote sensing, and transgenic experiments to study natural loss-of-function alleles associated with drought histories in wild
. The genes we identified exhibit population genetic signatures of parallel molecular evolution, selection for loss-of-function, and shared associations with flowering time phenotypes in directions consistent with longstanding adaptive hypotheses seven times more often than expected by chance. We then confirmed predicted phenotypes experimentally in transgenic knockout lines. These findings reveal the importance of drought timing to explain the evolution of alternative drought tolerance strategies and further challenge popular assumptions about the adaptive value of genetic loss-of-function in nature. These results also motivate improved species-wide sequencing efforts to better identify loss-of-function variants and inspire new opportunities for engineering climate resilience in crops.
Non-Hormonal Contraception Howard, Sarah Anne; Benhabbour, Soumya Rahima
Journal of clinical medicine,
07/2023, Letnik:
12, Številka:
14
Journal Article
Recenzirano
Odprti dostop
While hormonal contraceptives are efficacious and available in several forms for women, perception of safety and concern over side effects are a deterrent for many. Existing non-hormonal ...contraceptives include permanent sterilization, copper intrauterine devices (IUDs), chemical/physical barriers such as spermicides and condoms, as well as traditional family planning methods including withdrawal and the rhythm method. Individuals who wish to retain their fertility in the future can achieve highest adherence and efficacy with long-acting, reversible contraceptives (LARCs), though there is only one, the copper IUD, that is non-hormonal. As rates of unintended pregnancies remain high with existing contraceptive options, it is becoming increasingly attractive to develop novel pregnancy prevention methods for both women and men. Non-hormonal contraceptives can target a variety of critical reproductive processes discussed here. This review focuses on identified non-hormonal contraceptive targets and subsequent drug candidates in development.
Resource corridors are not new concepts. Corridors such as the Maputo Development Corridor, the Walvis Bay Development Corridor and TRIDOM have been active in different regions in Africa. The ...potential for shared infrastructure to support sustainable development has been widely discussed and debated by spatial and development partners. These initiatives present a vehicle to transform and ensure equitable distribution of benefits from sector specific operations. This is evident in the recent resurgence of interest in resource corridors, as highlighted by their position in numerous development and regional strategies. Those featuring resource corridors include the New Partnership for African Development (NEPAD), the mining policy framework developed for the United Nations by the Inter-Governmental forum on Mining, Minerals, Metals and Sustainable Development and more recently the Africa Mining Vision 2050, developed for the African Union by UNECA. Corridors are also on the agendas of regional entities, such as the African Development Bank, the Asian Development Bank and the East African and Southern African Development Communities.
The aim of the study was to analyze the clinical and imaging characteristics of primary intrathoracic malignant peripheral nerve sheath tumors (MPNSTs).
In this institutional review board ...(IRB)-approved retrospective study, clinical and imaging features of 15 patients (eight men; mean age 50 years range 18-83) with pathologically proven malignant peripheral nerve sheath tumors seen from January 1999 to December 2011 were analyzed. Imaging features (CT in 15, MRI in 5 and PET/CT in 4) of primary tumors were evaluated by three radiologists and correlated with clinical management.
Of the 15 tumors, six were located in the mediastinum (two each in anterior, middle and posterior mediastinum), four in chest wall, two were paraspinal, and three in the lung. Four patients had neurofibromatosis-1 (NF1); four tumors had heterologous rhabdomyoblastic differentiation (malignant triton tumor). Masses typically were elongated along the direction of nerves, with mean size of 11 cm. The masses were hypo- or isodense to muscles on CT, isointense on T1-weighted images, hyperintense on T2-weighted images and intensely fluorodeoxyglucose (FDG) avid (mean standardized uptake value SUV
of 10.5 range 4.4-23.6). Necrosis and calcification was seen in four tumors each. Finding of invasion of adjacent structures on imaging led to change in management in seven patients; patients with invasion received chemoradiation.
Intrathoracic MPNSTs appear as large elongated masses involving mediastinum, lung or chest wall. Radiological identification of invasion of adjacent structures is crucial and alters therapy, with patients with invasion receiving neoadjuvant or adjuvant chemoradiation.
Patient-centered outcomes research seeks to answer patient-centered questions. The process includes varied locations and individuals throughout the care continuum to address individual differences ...and constraints in implementation and dissemination.
This paper intends to answer this question: do academic nurses practice what they preach by assisting patient-centered outcomes research and researchers through their engagement with patients, caregivers, and other community stakeholder partners in nursing research?
This paper provides an overview of how academic nurses in a single institution (the University of Texas Medical Branch at Galveston School of Nursing) began to embrace patient-centered outcomes research.
Whether academic nurses are practicing what they preach in terms of patient-centered outcomes research remains uncertain. More examples from academia are required to make that determination. Academic nurses worldwide have embarked on a steep learning curve to embrace patient-centered outcomes research. This journey will require patience and a systematic strategy.
Due to the versatility of the in situ forming implant (ISFI) drug delivery system, it is crucial to understand the effects of formulation parameters for clinical translation. We utilized ultrasound ...imaging and pharmacokinetics (PK) in mice to understand the impact of administration route, injection volume, and drug loading on ISFI formation, degradation, and drug release in mice. Placebo ISFIs injected subcutaneously (SQ) with smaller volumes (40 μL) exhibited complete degradation within 30-45 days, compared to larger volumes (80 μL), which completely degraded within 45-60 days. However, all dolutegravir (DTG)-loaded ISFIs along the range of injection volumes tested (20-80 μL) were present at 90 days post-injection, suggesting that DTG can prolong ISFI degradation. Ultrasound imaging showed that intramuscular (IM) ISFIs flattened rapidly post administration compared to SQ, which coincides with the earlier T
for drug-loaded IM ISFIs. All mice exhibited DTG plasma concentrations above four times the protein-adjusted 90% inhibitory concentration (PA-IC90) throughout the entire 90 days of the study. ISFI release kinetics best fit to zero order or diffusion-controlled models. When total administered dose was held constant, there was no statistical difference in drug exposure regardless of the route of administration or number of injections.
Novel drugs targeting molecular pathways involved in tumor development have revolutionized cancer treatment. Radiologists often focus on therapeutic response when evaluating cancer patients and may ...miss important signs of drug toxicity. This article familiarizes radiologists with the complications of molecular targeted agents in abdominal solid organs, enabling early identification and appropriate intervention and thus reducing patient morbidity and mortality.
Knowledge of the common abdominal toxicities--including hepatitis, cholecystitis, pancreatitis, fluid retention, and infection--is crucial for early diagnosis, which may spare patients devastating complications or the need for surgery.
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