Primordia initiation of mushroom (Agaricus bisporus) strains on axenic casing materials

The mushroom (Agaricus bisporus) has a requirement for a ‘‘casing layer’’ that has specific physical, chemical and microbiological properties which stimulate and promote the initiation of primordia. Some of these primordia then may develop further into sporophores, involving differentiation of tissue. Wild and commercial strains of A. bisporus were cultured in axenic and nonaxenic microcosms, using a rye grain substrate covered by a range of organic and inorganic casing materials. In axenic culture, A. bisporus (commercial strain A15) was capable of producing primordia and mature sporophores on charcoal (wood and activated), anthracite coal, lignite and zeolite, but not on bark, coir, peat, rockwool, silica or vermiculite. Of six strains tested, only the developmental variant mutant, B430, produced rudimentary primordia on axenic peat-based casing material. However, none of these rudimentary primordia developed differentiated tissues or beyond 4 mm diameter, either on axenic casing material in the microcosms or in larger-scale culture. In larger-scale, nonaxenic culture, strain B430 produced severely malformed but mature sporophores in similar numbers to those of other strains. Typically, 3–6% of primordia developed into mature sporophores, but significant differences in this proportion, as well as in the numbers of primordia produced, were recorded between 12 A. bisporus strains

Negotiation in strategy making teams : group support systems and the process of cognitive change

This paper reports on the use of a Group Support System (GSS) to explore at a micro level some of the processes manifested when a group is negotiating strategy-processes of social and psychological negotiation. It is based on data from a series of interventions with senior management teams of three operating companies comprising a multi-national organization, and with a joint meeting subsequently involving all of the previous participants. The meetings were concerned with negotiating a new strategy for the global organization. The research involved the analysis of detailed time series data logs that exist as a result of using a GSS that is a reflection of cognitive theory

Gaps in benefits, awareness, and comprehension that leave those with long COVID vulnerable.

ObjectivesThe COVID-19 pandemic has left many suffering from long COVID, an episodic and debilitating chronic condition affecting people's ability to work and manage medical expenses. Though the Biden Administration has committed to conducting research and building support programs to alleviate the strain on those affected, in practice, static eligibility criteria for unemployment and disability benefits, patchy insurance coverage, and insufficient paid leave programs have left many people vulnerable. Given the magnitude of long COVID and the dearth to date of large-scale studies about its financial consequences, a focused qualitative analysis of lived experiences is warranted to understand and highlight gaps in the policy landscape.MethodsWe conducted in-depth semi-structured interviews from 2020 to 2022 with 25 people with experience of long COVID living predominately in the Midwest.ResultsOur inductive analysis revealed ways people became financially exhausted by uncertain medical care costs and precarious employment that left them trying, often alone, to access benefits. People described both experiences with workplace benefits and attempts to access federal benefits to address unstable employment situations created by protracted and uncertain functional impairments.DiscussionWe explore pre- and post-pandemic era unemployment, disability, and insurance policies and offer recommendations for better supporting people with long COVID

The PULSAR Specialist Care protocol: a stepped-wedge cluster randomized control trial a training intervention for community mental health teams in recovery-oriented practice

Background: Recovery features strongly in Australian mental health policy; however, evidence is limited for the efficacy of recovery-oriented practice at the service level. This paper describes the Principles Unite Local Services Assisting Recovery (PULSAR) Specialist Care trial protocol for a recovery-oriented practice training intervention delivered to specialist mental health services staff. The primary aim is to evaluate whether adult consumers accessing services where staff have received the intervention report superior recovery outcomes compared to adult consumers accessing services where staff have not yet received the intervention. A qualitative sub-study aims to examine staff and consumer views on implementing recovery-oriented practice. A process evaluation sub-study aims to articulate important explanatory variables affecting the interventions rollout and outcomes. Methods: The mixed methods design incorporates a two-step stepped-wedge cluster randomized controlled trial (cRCT) examining cross-sectional data from three phases, and nested qualitative and process evaluation sub-studies. Participating specialist mental health care services in Melbourne, Victoria are divided into 14 clusters with half randomly allocated to receive the staff training in year one and half in year two. Research participants are consumers aged 18-75 years who attended the cluster within a previous three-month period either at baseline, 12 (step 1) or 24 months (step 2). In the two nested sub-studies, participation extends to cluster staff. The primary outcome is the Questionnaire about the Process of Recovery collected from 756 consumers (252 each at baseline, step 1, step 2). Secondary and other outcomes measuring well-being, service satisfaction and health economic impact are collected from a subset of 252 consumers (63 at baseline; 126 at step 1; 63 at step 2) via interviews. Interview based longitudinal data are also collected 12 months apart from 88 consumers with a psychotic disorder diagnosis (44 at baseline, step 1; 44 at step 1, step 2). cRCT data will be analyzed using multilevel mixed-effects modelling to account for clustering and some repeated measures, supplemented by thematic analysis of qualitative interview data. The process evaluation will draw on qualitative, quantitative and documentary data. Discussion: Findings will provide an evidence-base for the continued transformation of Australian mental health service frameworks toward recovery

Less is more: Low expression of MT1-MMP is optimal to promote migration and tumourigenesis of breast cancer cells

Background: Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease implicated in metastatic progression ostensibly due to its ability to degrade extracellular matrix (ECM) components and allow migration of cells through the basement membrane. Despite in vitro studies demonstrating this principle, this knowledge has not translated into the use of MMP inhibitors (MMPi) as effective cancer therapeutics, or been corroborated by evidence of in vivo ECM degradation mediated by MT1-MMP, suggesting that our understanding of the role of MT1-MMP in cancer progression is incomplete. Methods: MCF-7 and MDA-MB 231 breast cancer cell lines were created that stably overexpress different levels of MT1-MMP. Using 2D culture, we analyzed proMMP-2 activation (gelatin zymography), ECM degradation (fluorescent gelatin), ERK signaling (immunoblot), cell migration (transwell/scratch closure/time-lapse imaging), and viability (colorimetric substrate) to assess how different MT1-MMP levels affect these cellular parameters. We also utilized Matrigel 3D cell culture and avian embryos to examine how different levels of MT1-MMP expression affect morphological changes in 3D culture, and tumourigenecity and extravasation efficiency in vivo. Results: In 2D culture, breast cancer cells expressing high levels of MT1-MMP were capable of widespread ECM degradation and TIMP-2-mediated proMMP-2 activation, but were not the most migratory. Instead, cells expressing low levels of MT1-MMP were the most migratory, and demonstrated increased viability and ERK activation. In 3D culture, MCF-7 breast cancer cells expressing low levels of MT1-MMP demonstrated an invasive protrusive phenotype, whereas cells expressing high levels of MT1-MMP demonstrated loss of colony structure and cell fragment release. Similarly, in vivo analysis demonstrated increased tumourigenecity and metastatic capability for cells expressing low levels of MT1-MMP, whereas cells expressing high levels were devoid of these qualities despite the production of functional MT1-MMP protein. Conclusions: This study demonstrates that excessive ECM degradation mediated by high levels of MT1-MMP is not associated with cell migration and tumourigenesis, while low levels of MT1-MMP promote invasion and vascularization in vivo

Patient-informed exploration of the aftermath of a diagnostic problem or mistake based on results of a national survey

IntroductionDespite the prevalence and devastating consequences of diagnostic breakdowns, there have been minimal efforts to systematically collect patient insight into diagnostic problems and mistakes. Collaborating with patient advocates to guide how patient-derived insights are interpreted and used is a critical, yet often overlooked, approach to identifying actionable solutions that speak to patients' priorities.ObjectiveWe collaborated with patient advocate co-authors to guide our understanding of findings from a mixed methods survey on diagnostic problems and mistakes, and report implications for patient engagement at three levels of action: (1) individual level before, during, after encounters (micro); (2) within health service delivery systems (meso); and (3) policy advocacy (macro).MethodsOur research team applied narrative elicitation methods to conduct a novel survey about Americans' diagnostic experiences in a national, population-based survey. We shared early results with patient co-authors who highlighted the importance of further exploring how health systems and clinicians address the aftermath of diagnostic mishaps. Based on their input, we summarized the quantitative and qualitative survey results about the aftermath and worked with our patient co-authors to explore how findings might inform actionable next steps, including efforts to catalyze patient action, quality improvement efforts, and policy reform.ResultsOf the 3,684 survey respondents, about a third (33.0%, 1,216/3,684) of screened households reported diagnostic problems and mistakes in the past four years involving either themselves (18.9%, 697/3,684) or someone close to them (14.1%, 519/3,684). In the aftermath of a diagnostic mishap, over a third reported that someone in the healthcare setting where the mistake occurred acknowledged the mistake (35.9%, 432/1,204). In qualitative findings, reports that the health system “did nothing” surfacing as the most common response. Patient co-authors confirmed the results resonated with their experiences and emphasized the need for health systems to take accountability when a mishap occurs and to take follow-up actions to prevent future mishaps.DiscussionPatients and care partners not only want and deserve acknowledgement of diagnostic problems or mistakes in their own care, they also want assurance that steps are being taken to prevent similar events from happening to others. Across micro-, meso-, and macro-levels of action, working with patients to understand and act on contributors to diagnostic breakdowns is aligned with high-reliability organizing principles

High-fidelity parallel entangling gates on a neutral atom quantum computer

The ability to perform entangling quantum operations with low error rates in a scalable fashion is a central element of useful quantum information processing. Neutral atom arrays have recently emerged as a promising quantum computing platform, featuring coherent control over hundreds of qubits and any-to-any gate connectivity in a flexible, dynamically reconfigurable architecture. The major outstanding challenge has been to reduce errors in entangling operations mediated through Rydberg interactions. Here we report the realization of two-qubit entangling gates with 99.5% fidelity on up to 60 atoms in parallel, surpassing the surface code threshold for error correction. Our method employs fast single-pulse gates based on optimal control, atomic dark states to reduce scattering, and improvements to Rydberg excitation and atom cooling. We benchmark fidelity using several methods based on repeated gate applications, characterize the physical error sources, and outline future improvements. Finally, we generalize our method to design entangling gates involving a higher number of qubits, which we demonstrate by realizing low-error three-qubit gates. By enabling high-fidelity operation in a scalable, highly connected system, these advances lay the groundwork for large-scale implementation of quantum algorithms, error-corrected circuits, and digital simulations.Comment: 5 pages, 4 figures. Methods: 13 pages, 10 figure

Effects of dietary energy density and supplemental rumen undegradable protein on intake, viscera, and carcass composition of lambs recovering from nutritional restriction

Variation in nutrition is a key determinant of growth, body composition, and the ability of animals to perform to their genetic potential. Depending on the quality of feed available, animals may be able to overcome negative effects of prior nutritional restriction, increasing intake and rates of tissue gain, but full compensation may not occur. A 2 × 3 × 4 factorial serial slaughter study was conducted to examine the effects of prior nutritional restriction, dietary energy density, and supplemental rumen undegradable protein (RUP) on intake, growth, and body composition of lambs. After an initial slaughter (n = 8), 124 4-mo-old Merino cross wethers (28.4 ± 1.8 kg) were assigned to either restricted (LO, 500 g/d) or unrestricted (HI, 1500 g/d) intake of lucerne and oat pellets. After 8 wk, eight lambs/group were slaughtered and tissue weights and chemical composition were measured. Remaining lambs were randomly assigned to a factorial combination of dietary energy density (7.8, 9.2, and 10.7 MJ/kg DM) and supplemental RUP (0, 30, 60, and 90 g/d) and fed ad libitum for a 12- to 13-wk experimental period before slaughter and analysis. By week 3 of the experimental period, lambs fed the same level of energy had similar DMI (g/d) and MEI (MJ/d) (P > 0.05), regardless of prior level of nutrition. Restricted-refed (LO) lambs had higher rates of fat and protein gain than HI lambs ( 0.05), regardless of prior level of nutrition. Restricted-refed (LO) lambs had higher rates of fat and protein gain than HI lambs (P P > 0.05). However, LO lambs were lighter and leaner at slaughter, with proportionally larger rumens and livers ( 0.05). However, LO lambs were lighter and leaner at slaughter, with proportionally larger rumens and livers (P P P P P > 0.05). Fat deposition was greatest in lambs fed 60 g/d supplemental RUP ( 0.05). Fat deposition was greatest in lambs fed 60 g/d supplemental RUP (P P > 0.05), with poorer nitrogen retention and proportionally heavier livers than P0 lambs ( 0.05), with poorer nitrogen retention and proportionally heavier livers than P0 lambs (