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The author reflects on the consequences of drink spiking in Australia. He explains that issues related to drug administration including drink spiking have been receiving attention from the press for a long period of time. He also discusses various consequences of drink spiking which is always associated to sexual assault.

This article looks at why the market for health care in the United States is distorted and how that makes the system inefficient. The author presents information on three efforts to describe, quantify and offer solutions to market distortions in health care but says the problem may be without a solution. He suggests that it may not be possible to please all the people some of the time no matter how noble the intent.

Control of gene expression by regulating mRNA translation is essential for proper growth and development in species ranging from yeast to mammals. Recently, translational regulation has also been implicated in neuronal function, where long-lasting changes in synaptic strength and the formation of memory require new protein synthesis. Crucial to both developmental and neurobiological function, translational control allows for the asymmetric distribution of gene products and a rapid and local response to stimulation – as discussed at a recent Serono Foundation EMBO Workshop held in Mallorca, Spain. [Copyright &y& Elsevier]

Focuses on dendritic messenger RNA translation. Regulation of activity-dependent transport into dendrites; Synapse-specific modifications; Role of untranslated domains in dendritic messages.

The majority of SARS-CoV-2 vaccines in use or advanced development are based on the viral spike protein (S) as their immunogen. S is present on virions as prefusion trimers in which the receptor binding domain (RBD) is stochastically open or closed. Neutralizing antibodies have been described against both open and closed conformations. The long-term success of vaccination strategies depends upon inducing antibodies that provide long-lasting broad immunity against evolving SARS-CoV-2 strains. Here, we have assessed the results of immunization in a mouse model using an S protein trimer stabilized in the closed state to prevent full exposure of the receptor binding site and therefore interaction with the receptor. We compared this with other modified S protein constructs, including representatives used in current vaccines. We found that all trimeric S proteins induced a T cell response and long-lived, strongly neutralizing antibody responses against 2019 SARS-CoV-2 and variants of concern P.1 and B.1.351. Notably, the protein binding properties of sera induced by the closed spike differed from those induced by standard S protein constructs. Closed S proteins induced more potent neutralizing responses than expected based on the degree to which they inhibit interactions between the RBD and ACE2. These observations suggest that closed spikes recruit different, but equally potent, immune responses than open spikes and that this is likely to include neutralizing antibodies against conformational epitopes present in the closed conformation. We suggest that closed spikes, together with their improved stability and storage properties, may be a valuable component of refined, next-generation vaccines. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are the treatment of choice for several cancers and can be associated with remarkable clinical benefit, but can also cause serious immune-related adverse events (irAEs). Management of rare and severe irAEs is challenged by an incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of fatal acute-onset gastro-intestinal (GI) hypomotility from myenteric plexus neuropathy following a single dose of ipilimumab plus nivolumab given for treatment of Merkel cell carcinoma (MCC). Case presentation: A 66-year-old man with recurrent metastatic MCC involving several organs (liver, bones and disseminated retroperitoneal lymphadenopathy) developed profound pharyngeal dysphagia and ileus that started 7 days after receiving a single administration of combination immune checkpoint blockade consisting of nivolumab (3 mg/kg) and low-dose ipilimumab (1 mg/kg). A swallowing study showed oropharyngeal dysfunction and aspiration. Imaging studies were consistent with diffuse intestinal paresis. An extensive work-up did not reveal obvious causes of these symptoms, and enteric plexopathy was suspected. Empiric immune suppressive therapy was initiated urgently. Despite an escalating immunosuppressive regimen that included high dose steroids, tacrolimus and therapeutic plasma exchange, no improvement in GI motility was seen and the patient suffered repeated episodes of aspiration. Seven weeks after the onset of GI hypomotility, the patient succumbed to sepsis from intestinal perforations. At autopsy, histologic specimens obtained from the entire GI tract (pharynx to rectum) showed near complete loss of ganglion cells within the myenteric and submucosal plexuses. An associated inflammatory infiltrate was not seen, suggesting a ‘burned out’ phase of illness. C4d complement deposition was found at the ganglionic sites, suggesting antibody-mediated pathogenesis. Remarkably, at sites of previously suspected Merkel cell metastases, no residual viable Merkel cell carcinoma was identified. Conclusions: GI-tract paresis due to myenteric neuritis is a rarely reported toxicity of ICIs. Because the window of reversibility is likely to be very brief, quick and decisive interventions are warranted. Subtle functional and anatomic perturbations of the myenteric nervous system from the use of ICIs may be more prevalent than realized and should be suspected and addressed in both clinical and investigational settings. [ABSTRACT FROM AUTHOR]

Context: Genome editing enables the introduction of beneficial sequence variants into the genomes of animals with high genetic merit in a single generation. This can be achieved by introducing variants into primary cells followed by producing a live animal from these cells by somatic cell nuclear transfer cloning. The latter step is associated with low efficiencies and developmental problems due to incorrect reprogramming of the donor cells, causing animal welfare concerns. Direct editing of fertilised one-cell embryos could circumvent this issue and might better integrate with genetic improvement strategies implemented by the industry. Methods: In vitro fertilised zygotes were injected with TALEN editors and repair template to introduce a known coat colour dilution mutation in the PMEL gene. Embryo biopsies of injected embryos were screened by polymerase chain reaction and sequencing for intended biallelic edits before transferring verified embryos into recipients for development to term. Calves were genotyped and their coats scanned with visible and hyperspectral cameras to assess thermal energy absorption. Key results: Multiple non-mosaic calves with precision edited genotypes were produced, including calves from high genetic merit parents. Compared to controls, the edited calves showed a strong coat colour dilution which was associated with lower thermal energy absorbance. Conclusions: Although biopsy screening was not absolutely accurate, non-mosaic, precisely edited calves can be readily produced by embryo-mediated editing. The lighter coat colouring caused by the PMEL mutation can lower radiative heat gain which might help to reduce heat stress. Implications: The study validates putative causative sequence variants to rapidly adapt grazing cattle to changing environmental conditions. With warming climates, grazing cattle are becoming increasingly heat stressed. Embryo-mediated genome editing provides a strategy to rapidly adapt cattle. It was successfully applied to introduce a mutation in the PMEL gene, known to lighten coat colour, which reduced thermal energy absorption and might help to reduce heat stress impacts. Photograph by G. Laible. [ABSTRACT FROM AUTHOR]

Many studies have documented the impact of maker experiences on children's learning, but few have examined how caregivers participate in maker activities in museums, both as facilitators of their children's learning and as learners in their own right. This qualitative study involved observations and interviews with 88 caregivers participating in a range of making and tinkering activities at a science museum. Aspects of the physical setting (including the arrangement and familiarity of tools and materials) and social setting (including facilitators' interactions with children versus caregivers) influenced whether families participated and the roles that caregivers played (observing, facilitating, or making). Across these roles, caregivers described benefitting as learners — by noticing their children's abilities and interests, learning new ways to support their children's learning, or fostering their own creativity. The results highlight strategies that museums can use to create inclusive maker activities that recognize caregivers' many roles and motivations during family visits. [ABSTRACT FROM AUTHOR]

This paper investigates the recently introduced data-driven correction reduced order model (DDC-ROM) in the numerical simulation of the quasi-geostrophic equations. The DDC-ROM uses available data to model the correction term that is generally used to represent the missing information in low-dimensional ROMs. Physical constraints are added to the DDC-ROM to create the constrained data-driven correction reduced order model (CDDC-ROM) in order to further improve its accuracy and stability. Finally, the DDC-ROM and CDDC-ROM are tested on time intervals that are longer than the time interval over which they were trained. The numerical investigation shows that, for low-dimensional ROMs, both the DDC-ROM and CDDC-ROM perform better than the standard Galerkin ROM (G-ROM) and the CDDC-ROM provides the best results. [ABSTRACT FROM AUTHOR]

This paper provides an overview of the new features of the finite element library deal.II, version 9.5. [ABSTRACT FROM AUTHOR]

In this article the author discusses the need for value adding and providing market intelligence service in the agricultural supply chain strategy of Tasmania. Topics include the value gap in the food production at farm gate and its value after processing and packing indicating the need for value-adding industry, views of several people including economist Neille Ferguson, and Peter Murden from Central Coast Council regarding the same, and innovation as a driver of sustainable economic growth.

Presents a letter to the editor in response to the article "Calendar" in the May 2003 issue.

Presents a pathologic case study of juvenile ossifying fibroma seen in a patient with swelling of the maxilla. Clinical history of the patient; Results of physical and laboratory examinations performed on the patient; Information on the illness.

The article shares the author's perspectives on the importance of business agriculture executives, to have the understanding and knowledge on the market trends, and outlines the challenges of continuous change in customer preferences and research and development projects.

Standard ROMs generally yield spurious numerical oscillations in the simulation of convection-dominated flows. Regularized ROMs use explicit ROM spatial filtering to decrease these spurious numerical oscillations. The Leray ROM is a recently introduced regularized ROM that utilizes explicit ROM spatial filtering of the convective term in the Navier–Stokes equations. This paper presents the numerical analysis of the finite element discretization of the Leray ROM. Error estimates for the ROM differential filter, which is the explicit ROM spatial filter used in the Leray ROM, are proved. These ROM filtering error estimates are then used to prove error estimates for the Leray ROM. Finally, both the ROM filtering error estimates and the Leray ROM error estimates are numerically investigated in the simulation of the two-dimensional Navier–Stokes equations with an analytic solution. [ABSTRACT FROM AUTHOR]

Somatic cell nuclear transfer (SCNT), commonly referred to as cloning, results in the generation of offspring that, except for mitochondrial DNA, are genetically identical to the nuclear donor. We previously used a genetically modified bovine cell line as the donor for SCNT and obtained a calf, named Daisy, that was born without a tail. To determine whether the missing tail was a result of the genetic modification, we performed recloning experiments by using either cells from a sacrificed pregnancy of a second clone (Daisy's 'twin' clone) or cells from tailless Daisy as donors for SCNT. Cloned fetuses from aborted pregnancies and a cloned live calf that died shortly after birth were examined and confirmed to all possess tails. Hence, the observed phenotype of Daisy's lacking tail is not due to the introduced transgene or a mutation present in the cell that was used for her production. Rather, the missing tail has most likely arisen from an epigenetic reprogramming error during development. [ABSTRACT FROM AUTHOR]

Presents a case of severe aminophylline intoxication in a premature infant. Information on the overdose tolerated by the infant; How the error in medication was made.

A single-channel method of recording eye movements, using two active electrodes, is described. Illustrations are presented of its accuracy, efficiency, and degree of common-mode rejection. The method appears to offer advantages in possible computer scoring of eye-movement data, as well as improvements in speed and accuracy of hand-scoring such data. [ABSTRACT FROM AUTHOR]

This paper presents a conforming finite element semi-discretization of the streamfunction form of the one-layer unsteady quasi-geostrophic equations, which are a commonly used model for large-scale wind-driven ocean circulation. We derive optimal error estimates and present numerical results. [ABSTRACT FROM AUTHOR]

Regulation of protein expression in neurons by controlling not only when, but where, mRNAs are translated is likely to play an important role in neuronal function. In this review I focus on the mRNA-binding proteins that control mRNA translation in neurons and how they may participate in local, synaptodendritic protein synthesis. [ABSTRACT FROM AUTHOR]