Telehealth services have helped enable continuity of care during the coronavirus pandemic. We aimed to investigate use and views towards telehealth among allied health clinicians treating people with ...musculoskeletal conditions during the pandemic.
Cross-sectional international survey of allied health clinicians who used telehealth to manage musculoskeletal conditions during the coronavirus pandemic. Questions covered demographics, clinician-related factors (e.g. profession, clinical experience and setting), telehealth use (e.g. proportion of caseload, treatments used), attitudes towards telehealth (Likert scale), and perceived barriers and enablers (open questions). Data were presented descriptively, and an inductive thematic content analysis approach was used for qualitative data, based on the Capability-Opportunity-Motivation Behavioural Model.
827 clinicians participated, mostly physiotherapists (82%) working in Australia (70%). Most (71%, 587/827) reported reduced revenue (mean (SD) 62% (24.7%)) since the pandemic commenced. Median proportion of people seen via telehealth increased from 0% pre (IQR 0 to 1) to 60% during the pandemic (IQR 10 to 100). Most clinicians reported managing common musculoskeletal conditions via telehealth. Less than half (42%) of clinicians surveyed believed telehealth was as effective as face-to-face care. A quarter or less believed patients value telehealth to the same extent (25%), or that they have sufficient telehealth training (21%). Lack of physical contact when working through telehealth was perceived to hamper accurate and effective diagnosis and management.
Although telehealth was adopted by allied health clinicians during the coronavirus pandemic, we identified barriers that may limit continued telehealth use among allied health clinicians beyond the current pandemic.
•Allied health clinicians rapidly adopted telehealth during the coronavirus pandemic.•They view telehealth as part of their clinical role.•However, most felt they lacked adequate training to deliver telehealth services.•And that telehealth is inferior to face-to-face care and undervalued by patients.•These barriers may limit use of telehealth beyond the pandemic.
Abstract For next-generation neutrinoless double beta decay experiments, extremely low backgrounds are necessary. An understanding of in-situ cosmogenic backgrounds is critical to the design effort. ...In-situ cosmogenic backgrounds impose a depth requirement and especially impact the choice of host laboratory. Often, simulations are used to understand background effects, and these simulations can have large uncertainties. One way to characterize the systematic uncertainties is to compare unalike simulation programs. In this paper, a suite of neutron simulations with identical geometries and starting parameters have been performed with Geant4 and MCNP, using geometries relevant to the LEGEND-1000 experiment. This study is an important step in gauging the uncertainties of simulations-based estimates. To reduce project risks associated with simulation uncertainties, a novel alternative shield of methane-doped liquid argon is considered in this paper for LEGEND-1000, which could achieve large background reduction without requiring significant modification to the baseline design.
The coronavirus disease 2019 (COVID-19) pandemic immediately and perhaps irrevocably impacted society at large, the provision of cardiovascular (CV) care, the function and staffing of hospitals, and ...CV clinicians. Initially many clinicians at all career stages rose to the challenges, and support and accolades were the initial societal response. Politicization of the public health response as well as widespread misinformation and disinformation all negatively impacted CV clinicians' roles as well diminished and, in some cases, eliminated their public and self-esteem. Unabated stress, disrespect, and a likely lack of emotional and physical respite may all have contributed to the Great Resignation. Insights gained from review of the COVID-19 pandemic may help inform changes to foster system resiliency and prepare for an improved response to the inevitable next stressor.
Estrogen receptor alpha (ERα) is a ligand-activated transcription factor. Upon estrogen stimulation, ERα recruits a number of coregulators, including both coactivators and corepressors, to the ...estrogen response elements, modulating gene activation or repression. Most coregulator complexes contain histone-modifying enzymes to control ERα target gene expression in an epigenetic manner. In addition to histones, these epigenetic modifiers can modify nonhistone proteins including ERα, thereby constituting another layer of transcriptional regulation. Here we show that SET and MYND domain containing 2 (SMYD2), a histone H3K4 and H3K36 methyltransferase, directly methylates ERα protein at lysine 266 (K266) both in vitro and in cells. In breast cancer MCF7 cells, SMYD2 attenuates the chromatin recruitment of ERα to prevent ERα target gene activation under an estrogen-depleted condition. Importantly, the SMYD2-mediated repression of ERα target gene expression is mediated by the methylation of ERα at K266 in the nucleus, but not the methylation of histone H3K4. Upon estrogen stimulation, ERα–K266 methylation is diminished, thereby enabling p300/cAMP response element-binding protein–binding protein to acetylate ERα at K266, which is known to promote ERα transactivation activity. Our study identifies a previously undescribed inhibitory methylation event on ERα. Our data suggest that the dynamic cross-talk between SMYD2-mediated ERα protein methylation and p300/cAMP response element-binding protein–binding protein-dependent ERα acetylation plays an important role in fine-tuning the functions of ERα at chromatin and the estrogen-induced gene expression profiles.
Few cross-sectional studies report iron deficiency (ID) prevalence in women of different race/ethnicity and ages in US or Canada.
We evaluated screening observations on women who participated between ...2001-2003 in a cross-sectional, primary care-based sample of adults ages ≥25 y whose observations were complete: race/ethnicity; age; transferrin saturation; serum ferritin; and HFE p.C282Y and p.H63D alleles. We defined ID using a stringent criterion: combined transferrin saturation <10% and serum ferritin <33.7 pmol/L (<15 μg/L). We compared ID prevalence in women of different race/ethnicity subgrouped by age and determined associations of p.C282Y and p.H63D to ID overall, and to ID in women ages 25-44 y with or without self-reported pregnancy.
These 62,685 women included 27,079 whites, 17,272 blacks, 8,566 Hispanics, 7,615 Asians, 449 Pacific Islanders, 441 Native Americans, and 1,263 participants of other race/ethnicity. Proportions of women with ID were higher in Hispanics and blacks than whites and Asians. Prevalence of ID was significantly greater in women ages 25-54 y of all race/ethnicity groups than women ages ≥55 y of corresponding race/ethnicity. In women ages ≥55 y, ID prevalence did not differ significantly across race/ethnicity. p.C282Y and p.H63D prevalence did not differ significantly in women with or without ID, regardless of race/ethnicity, age subgroup, or pregnancy.
ID prevalence was greater in Hispanic and black than white and Asian women ages 25-54 y. p.C282Y and p.H63D prevalence did not differ significantly in women with or without ID, regardless of race/ethnicity, age subgroup, or pregnancy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal and characterized by early metastasis. Oncogenic
mutations prevail in 95% of PDAC tumors and co-occur with genetic alterations in the
...tumor suppressor in nearly 70% of patients. Most
alterations are missense mutations that exhibit gain-of-function phenotypes that include increased invasiveness and metastasis, yet the extent of direct cooperation between
effectors and mutant p53 remains largely undefined. We show that oncogenic
effectors activate CREB1 to allow physical interactions with mutant p53 that hyperactivate multiple prometastatic transcriptional networks. Specifically, mutant p53 and CREB1 upregulate the prometastatic, pioneer transcription factor
, activating its transcriptional network while promoting WNT/β-catenin signaling, together driving PDAC metastasis. Pharmacologic CREB1 inhibition dramatically reduced
and β-catenin expression and dampened PDAC metastasis, identifying a new therapeutic strategy to disrupt cooperation between oncogenic
and mutant p53 to mitigate metastasis. SIGNIFICANCE: Oncogenic
and mutant p53 are the most commonly mutated oncogene and tumor suppressor gene in human cancers, yet direct interactions between these genetic drivers remain undefined. We identified a cooperative node between oncogenic
effectors and mutant p53 that can be therapeutically targeted to undermine cooperation and mitigate metastasis.
.
This article introduces an agent-based modeling laboratory for investigating how evolving hazard information, propagated through forecaster, media, public official, and peer information networks, ...affects patterns of public protective-action decisions during hurricane threats. The model, called CHIME ABM, provides a platform for integrating atmospheric science, social science, and computer and information science knowledge and data to explore the complex socio-ecological dynamics of modern hazard information and decision systems from a new perspective. First, the model's interdisciplinary conceptualization and implementation is described. Results are then presented from experiments demonstrating the model's behaviors and comparing patterns of evacuation decisions when key agent parameters and the geographical population distribution, forecast skill, and storm are varied. The article illustrates how this type of theoretically and empirically informed digital laboratory can be used to develop new insights into the interactions among environmental hazards, information flow, protective decisions, and societal outcomes.
•Agent-based modeling helps elucidate how evolving hazards, information, and decisions interact.•Information propagates across space, time, and people to influence evacuation patterns.•As threat uncertainty decreases, feedback loops rapidly increase risk assessments.
The unprecedented use of Earth's resources by humans, in combination with
increasing natural variability in natural processes over the past century, is
affecting the evolution of the Earth system. To ...better understand natural
processes and their potential future trajectories requires improved
integration with and quantification of human processes. Similarly, to
mitigate risk and facilitate socio-economic development requires a better
understanding of how the natural system (e.g. climate variability and
change, extreme weather events, and processes affecting soil fertility)
affects human processes. Our understanding of these interactions and feedback
between human and natural systems has been formalized through a variety of
modelling approaches. However, a common conceptual framework or set of
guidelines to model human–natural-system feedbacks is lacking. The presented
research lays out a conceptual framework that includes representing
model coupling configuration in combination with the frequency of interaction
and coordination of communication between coupled models. Four different
approaches used to couple representations of the human and natural system are
presented in relation to this framework, which vary in the processes
represented and in the scale of their application. From the development and
experience associated with the four models of coupled human–natural systems,
the following eight lessons were identified that if taken into account by
future coupled human–natural-systems model developments may increase their
success: (1) leverage the power of sensitivity analysis with models,
(2) remember modelling is an iterative process, (3) create a common language,
(4) make code open-access, (5) ensure consistency, (6) reconcile
spatio-temporal mismatch, (7) construct homogeneous units, and
(8) incorporating feedback increases non-linearity and variability. Following a discussion of
feedbacks, a way forward to expedite model coupling and increase the
longevity and interoperability of models is given, which suggests the use of
a wrapper container software, a standardized applications programming
interface (API), the incorporation of standard names, the mitigation of sunk costs by
creating interfaces to multiple coupling frameworks, and the adoption of
reproducible workflow environments to wire the pieces together.
Germ cell fate in mice is induced in pluripotent epiblast cells in response to signals from extraembryonic tissues. The specification of approximately 40 founder primordial germ cells and their ...segregation from somatic neighbours are important events in early development. We have proposed that a critical event during this specification includes repression of a somatic programme that is adopted by neighbouring cells. Here we show that Blimp1 (also known as Prdm1), a known transcriptional repressor, has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. Blimp1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. Furthermore, our genetic lineage-tracing experiments indicate that the Blimp1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK