Growing interest in exploring mechanically mediated biological phenomena has resulted in cell culture substrates and 3D matrices with variable stiffnesses becoming standard tools in biology labs. ...However, correlating stiffness with biological outcomes and comparing results between research groups is hampered by variability in the methods used to determine Young's (elastic) modulus, E, and by the inaccessibility of relevant mechanical engineering protocols to most biology labs. Here, we describe a protocol for measuring E of soft 2D surfaces and 3D hydrogels using atomic force microscopy (AFM) force spectroscopy. We provide instructions for preparing hydrogels with and without encapsulated live cells, and provide a method for mounting samples within the AFM. We also provide details on how to calibrate the instrument, and give step-by-step instructions for collecting force-displacement curves in both manual and automatic modes (stiffness mapping). We then provide details on how to apply either the Hertz or the Oliver-Pharr model to calculate E, and give additional instructions to aid the user in plotting data distributions and carrying out statistical analyses. We also provide instructions for inferring differential matrix remodeling activity in hydrogels containing encapsulated single cells or organoids. Our protocol is suitable for probing a range of synthetic and naturally derived polymeric hydrogels such as polyethylene glycol, polyacrylamide, hyaluronic acid, collagen, or Matrigel. Although sample preparation timings will vary, a user with introductory training to AFM will be able to use this protocol to characterize the mechanical properties of two to six soft surfaces or 3D hydrogels in a single day.
The Late Heavy Bombardment Bottke, William F; Norman, Marc D
Annual review of earth and planetary sciences,
08/2017, Letnik:
45, Številka:
1
Journal Article
Recenzirano
Heavily cratered surfaces on the Moon, Mars, and Mercury show that the terrestrial planets were battered by an intense bombardment during their first billion years or more, but the timing, sources, ...and dynamical implications of these impacts are controversial. The Late Heavy Bombardment refers to impact events that occurred after stabilization of the planetary lithospheres such that they could be preserved as craters and basins. Lunar melt rocks and meteorite shock ages point toward a discrete episode of elevated impact flux between ∼3.5 and ∼4.0-4.2 Ga, and a relative quiescence between ∼4.0-4.2 and ∼4.4 Ga. Evidence from Precambrian impact spherule layers suggests that a long-lived tail of terrestrial impactors lasted to ∼2.0-2.5 Ga. Dynamical models that include populations residual from primary accretion and destabilized by giant planet migration can potentially account for the available observations, although all have pros and cons. The most parsimonious solution to match constraints is a hybrid model with discrete early, post-accretion and later, planetary instability-driven populations of impactors.
There are significant differences at many levels in the use of intrauterine levonorgestrel for contraception when compared to using it as a therapeutic.
It is 100 years since the discovery of ...oestrogen and nearly that since the discovery of progesterone. It is over 50 years since the concept of using intrauterine progesterone. Ten years after its synthesis, the research using levonorgestrel as an intrauterine agent was introduced.
The pharmacodynamics and pharmacokinetics of LNG-IUSs and the LNG-IUS 52 mg in particular explain why intrauterine LNG is so highly effective for contraception. When intrauterine LNG is used therapeutically it should ideally be based on clinical monitoring of the pathology being treated rather than a fixed time period While the LNG-IUS 52 mg is probably required for most medical conditions, consideration should be given for using the LNG-IUS 13.5 mg for hyperplasia and endometrial protection during oestrogen therapy and for older women who appear more prone to a low rate of LNG induced breast cancer, although there is not yet an official indication for this.
The desire for fertility control, therapy for various genital pathological conditions and reduction of repeated endometrial decidualization and inflammatory breakdown and its consequences, and menopausal problems can be aided by intrauterine LNG. This review explains how a contraceptive also became a WHO listed essential medicine.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The clinician–scientist role is critical to the future of health care, and in 2010, the Carnegie Report on Educating Physicians focused attention on the professional identity of practicing ...clinicians. Although limited in number, published studies on the topic suggest that professional identity is likely a critical factor that determines career sustainability. In contrast to clinicians with a singular focus on clinical practice, clinician–scientists combine two major disciplines, clinical medicine and scientific research, to bridge discovery and clinical care. Despite its importance to advancing medical practice, the clinician–scientist career faced a variety of threats, which have been identified recently by the 2014 National Institutes of Health Physician Scientist Workforce. Yet, professional identity development in this career pathway is poorly understood. This Perspective focuses on the challenges to the clinician–scientist’s professional identity and its development. First, the authors identify the particular challenges that arise from the different cultures of clinical care and science and the implications for clinician–scientist professional identity formation. Next, the authors synthesize insights about professional identity development within a dual-discipline career and apply their analysis to a discussion about the implications for clinician–scientist identity formation. Although not purposely developed to address identity formation, the authors highlight those elements within clinician–scientist training and career development programs that may implicitly support identity development. Finally, the authors highlight a need to identify empirically the elements that compose and determine clinician–scientist professional identity and the processes that shape its formation and sustainability.
The menstrual cycle appears to have evolved in humans and some other species to improve reproductive efficiency by enabling progesterone production without the presence of the fetus. This phenomenon ...is termed spontaneous decidualization. Repeated menstruation is produced in modern women because of better general health and having fewer pregnancies later in life and limiting breast feeding. The repeated breakdown of a progesterone primed endometrium releases an inflammatory cascade which appears to have short and long term adverse consequences. Repetitive modern menstruation is no longer a sign of good general and reproductive health but a harbinger of possible future health problems. Cyclical menstruation has no intrinsic biological value or necessity in modern life. Spontaneous decidualization can be prevented by using estrogen-progestin combinations or progestins on their own. Newer and safer hormonal products are now available and should become even safer in the future. Hormonal suppression of spontaneous decidualization should be encouraged in adolescent and young women as a health promotional option.
Hearing loss affects nearly 1.6 billion people and is the third-leading cause of disability worldwide. Chronic kidney disease (CKD) is also a common condition that is associated with adverse clinical ...outcomes and high health-care costs. From a developmental perspective, the structures responsible for hearing have a common morphogenetic origin with the kidney, and genetic abnormalities that cause familial forms of hearing loss can also lead to kidney disease. On a cellular level, normal kidney and cochlea function both depend on cilial activities at the apical surface, and kidney tubular cells and sensory epithelial cells of the inner ear use similar transport mechanisms to modify luminal fluid. The two organs also share the same collagen IV basement membrane network. Thus, strong developmental and physiological links exist between hearing and kidney function. These theoretical considerations are supported by epidemiological data demonstrating that CKD is associated with a graded and independent excess risk of sensorineural hearing loss. In addition to developmental and physiological links between kidney and cochlear function, hearing loss in patients with CKD may be driven by specific medications or treatments, including haemodialysis. The associations between these two common conditions are not commonly appreciated, yet have important implications for research and clinical practice.
ObjectiveTo assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain.DesignSystematic review.Data sourcesCENTRAL, EMBASE and MEDLINE.Main ...outcomes and measuresOpioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events.Study selection criteria and methodsWe included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome.ResultsEligible studies included five randomised trials (all enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) −3.4 milligram morphine equivalent (MME); 95% CI (CI) −12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD −0.18 cm; 95% CI −0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD −0.22 cm; 95% CI −0.4 to −0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD −1%; 95% CI −4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD −22.5 MME; 95% CI −43.06 to −1.97).ConclusionOpioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.PROSPERO registration numberCRD42018091098.
Electronic health tools provide little value if the intended users lack the skills to effectively engage them. With nearly half the adult population in the United States and Canada having literacy ...levels below what is needed to fully engage in an information-rich society, the implications for using information technology to promote health and aid in health care, or for eHealth, are considerable. Engaging with eHealth requires a skill set, or literacy, of its own. The concept of eHealth literacy is introduced and defined as the ability to seek, find, understand, and appraise health information from electronic sources and apply the knowledge gained to addressing or solving a health problem. In this paper, a model of eHealth literacy is introduced, comprised of multiple literacy types, including an outline of a set of fundamental skills consumers require to derive direct benefits from eHealth. A profile of each literacy type with examples of the problems patient-clients might present is provided along with a resource list to aid health practitioners in supporting literacy improvement with their patient-clients across each domain. Facets of the model are illustrated through a set of clinical cases to demonstrate how health practitioners can address eHealth literacy issues in clinical or public health practice. Potential future applications of the model are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Simulated data, validity reports and a firefighter predictive validation study are used to examine validity bias created by three common selection problems-range restriction, applicant and incumbent ...attrition, and nonlinearity created by compression of high selection test scores. Top 20% selection samples drawn from an applicant pool with known validity coefficients demonstrate that the sample validity estimates of the three predictors are differentially biased in both magnitude and direction, depending on the selection strategy used. Concurrent validity designs generally favor novel predictors. Corrections for direct range restriction across situations were mostly ineffectual. With proper scaling, corrections for indirect range restriction are accurate, but cross-variable biasing effects can occur when score distributions of the individual predictors differ. Many of the biases found in the simulation results are demonstrated in a firefighter predictive validation study where variations of Pearson-Thorndike range corrected validities and a full information maximum likelihood (FIML), approaches are all compared as validity assessments. With normalized predictors, both Pearson and FIML methods show that a test of general mental ability and physically demanding job tasks predicted firefighter performance throughout the 30-year study, with no evidence of interactions or a leveling of performance at high test scores.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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