Optimization of the regularization parameter in the Dual Annealing method used for the reconstruction of energy spectrum of electron beam generated by the AQURE mobile accelerator.

INTRODUCTION: The shape of the energy spectrum is an essential component of any electron beam Monte Carlo model. Due to specialized equipment and the long measurement time for the direct methods for determining the energy spectrum, attractive alternatives are backward spectrum reconstructions from the measured data. One such approach is solving the first-degree Fredholm integral equation with appropriate regularization. It makes it possible to calculate the depth distribution as the sum of the distributions from monoenergetic beams. This study aims to determine the optimal value of the regularization parameter for the problem of determining the spectrum of the electron beam produced by a mobile accelerator used during intraoperative radiotherapy. MATERIAL AND METHODS: The Geant4 package was used to generate the distributions of deep doses for monoenergetic beams for two models with different degrees of complexity, i.e. simple (theoretical) and full (for the mobile accelerator). The dose distributions for four different shapes of energy spectrum (for each model) were obtained similarly. They were established as the reference data for further calculations. The Dual Annealing optimization method was used to obtain the reconstructed spectrum. The multiple optimizations that differ by the regularization parameter (ranging from 0 to 1) were performed. For each reconstruction, similarity indicators of the energy spectrum and the dose distribution to the referenced data were calculated to determine the optimal regularization parameters. RESULTS: Optimal regularization parameters determined by similarity indicators for the spectrum and the dose distribution differ for geometry models considered in the study. The regularization parameter for the simple geometry ranged from 0.03 to 0.05, while for full geometry, they were from 0.05 to 0.06. The results for conventional linear accelerators found in the literature range from 0.5 to 1.1. CONCLUSION: The Dual Annealing optimization method can be effectively used to solve the Fredholm equation with Tikhonov regularization to reconstruct an electron beam's energy spectrum. The regularization parameter value depends on the beam-forming system. Its value for the mobile accelerator considered in the study ranges from 0.05 to 0.06, depending on the nominal beam energy value.

Policies to prevent zoonotic spillover: protocol for a systematic scoping review of evaluative evidence.

INTRODUCTION: The increasing incidence of pathogen transmission from animals to humans (zoonotic spillover events) has been attributed to behavioural practices and ecological and socioeconomic change. As these events sometimes involve pathogens with epidemic or pandemic potential, they pose a serious threat to population health. Public policies may play a key role in preventing these events. The aim of this review is to identify evaluations of public policies that target the determinants of zoonotic spillover, examining approaches taken to evaluation, choice of outcomes measures and evidence of effectiveness. Our approach to identifying and analysing this literature will be informed by a One Health lens, acknowledging the interconnectedness of human, animal and environmental health. METHODS AND ANALYSIS: A systematic scoping review methodology will be used. To identify articles, we will search Medline, SCOPUS, Web of Science and Global Health in May 2021 using search terms combining animal health and the animal-human interface, public policy, prevention and zoonoses. We will screen titles and abstracts and extract data according to published guidelines for scoping reviews. All evaluations of public policies aiming to prevent zoonotic spillover events will be eligible for inclusion. We will summarise key data from each study, mapping policies along the spillover pathway and outlining the range of policies, approaches to evaluation and outcome measures. Review findings will provide a useful reference for researchers and practitioners, outlining the state of the evaluative evidence around policies to prevent zoonotic spillover. ETHICS AND DISSEMINATION: Formal ethical approval is not required, because the study does not involve primary data collection. The findings of this study will be disseminated through a peer-reviewed publication, presentations and summaries for key stakeholders.

Economic implications of hip fracture: health service use, institutional care and cost in Canada.

As the burden of illness associated with hip fracture extends beyond the initial hospitalization, a longitudinal 1 year cohort study was used to analyze levels of health service use, institutional care and their associated costs, and to examine patient and residency factors contributing to overall 1 year cost. Patients in the study were aged 50 year and over, and had been admitted to an acute care facility for hip fracture in the Hamilton-Wentworth region of Canada from 1 April 1995 to 31 March 1996. Health care resources assessed included initial hospitalization, rehospitalization, rehabilitation, chronic care, home care, long-term care (LTC) and informal care. Regression analysis was used to determine the effects of age, gender, residence, survival and days of follow-up on 1 year cost. The mean 1 year cost of hip fracture for the 504 study patients was 26,527 Canadian dollars (95% Cl: $24,564-$28,490). One year costs were significantly different for patients who returned to the community ($21,385), versus those who were transferred to ($44,156), or readmitted to LTC facilities ($33,729) (p < 0.001). Initial hospitalization represented 58% of 1 year cost for community-dwelling patients, compared with 27% for LTC residents. Only 59.4% of community-dwelling patients resided in the community 1 year following hip fracture, and 5.6% of patients who survived their first fracture experienced a subsequent hip fracture. Linear regression indicated place of residence, age and survival were all important contributors to 1 year cost (p < 0.001). While the average 1 year cost of care was $26,527, the overall cost varied depending on a patient's place of residence, age, and survival to 1 year. Annual economic implications of hip fracture in Canada are $650 million and are expected to rise to $2.4 billion by 2041.

Regulating biotechnology: a rational-political model of policy development.

While technology assessment is seen as a mechanism for achieving effective and efficient use of health care resources, it has not as yet made the impact on policy decisions that its potential would suggest. Considerable barriers have been encountered in translating assessment results into policy concerning the adoption and use of technologies, with 'political' factors often being decisive. This paper places technology assessment in the content of the policy process to clarify both (a) how conflicting interests and organizational features can often hinder the selection of optimal policies, and (b) the potential roles technology assessment could nonetheless play. The resulting framework is termed the 'rational-political' model of policy development. The paper uses the example of policy making about the regulation of biotechnology, drawing on information from a survey of decision-makers (n = 561) involved in issues concerning the development, approval, and payment for pharmaceutical products.

Technology acquisition in Canadian hospitals: how are we doing?

We surveyed attitudes of decision makers involved in making decisions about technology acquisition in hospitals, receiving replies from 989 (72%) anglophone respondents and 201 (68%) from francophone respondents. Respondents split on whether to try unverified procedures, strongly agreed that medical technology should be evaluated, and expressed a desire for technology assessment data. The quality of health care, need, and compatibility with the institution's role and mission were seen as the most important factors affecting acquisitions. Our study suggests that half the battle has been won; decision makers appear convinced that technologies must be evaluated. Organizational mechanisms, however, may still be required to ensure implementation.

Technology acquisition in Canadian hospitals: how is it done, and where is the information coming from?

A 1990 nation-wide survey on technology acquisition in Canadian hospitals, based on 509 Anglophone and 55 Francophone hospital questionnaires and 193 hospital equipment request forms, revealed that 53% of capital funds were used to replace existing equipment, with the remainder spent on new purchases. However, very little regional planning was taking place. Most of the institutional acquisition decisions were made by committees, 17% of which were classified as medical staff, 25.1% as administrative, 32.4% as board committees and 22.5% as mixed. Although administration was heavily represented, medical staff were frequently present and nursing was just as likely to have at least minimal representation. However, technical experts usually played a minimal role. This omission, combined with the limited information asked for on equipment request forms and the limited availability and use of technology assessment information, suggests that acquisition decisions in many Canadian hospitals are likely to be based on inadequate information.

Apolipoprotein (apo) B and apoII gene expression are both estrogen-responsive in chick embryo liver but only apoII is estrogen-responsive in kidney.

Estrogen regulates the hepatic synthesis of a variety of proteins required for egg yolk production in oviparous vertebrates. In chickens, two of these proteins, apolipoprotein (apo) B and apoII, comprise the major protein components of specialized very low density lipoprotein particles that transport triacylglycerols and cholesterol to the developing egg yolk. In the adult, apoB is synthesized constitutively in liver, small intestine, and kidney but is estrogen-responsive only in the liver. In this work we have examined the embryonic expression of the apoB and apoII genes in yolk sac, liver, kidney, and small intestine. The 14 kb apoB mRNA was first detected at day 3 of development in vascular yolk sac, a tissue involved in the transfer of yolk lipids into the embryonic circulation. Constitutive apoB mRNA expression was detectable in liver at day 6.5 and in kidney at day 7.5, but in intestine was barely detectable before hatching. The hepatic apoB gene acquired estrogen-responsiveness at day 6.5 and its hormone-dependent expression increased throughout development in concert with the estrogen-responsive expression of the apoII gene. In contrast, the constitutively expressed apoB gene in kidney remained unresponsive to estrogen. Surprisingly, the apoII gene was found to be responsive to estrogen in both the embryonic kidney and small intestine. ApoII mRNA induction by estrogen in kidney at day 11 was at 10% of the level in the liver but estrogen-responsiveness decreased later in development and was low in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of myelin basic protein gene transcription in normal and shiverer mutant mice.

We describe the measurement of myelin basic protein gene transcription rate, and of the accumulation of both mature mRNA and total transcripts from the myelin basic protein gene in brains from mice of wild-type and homozygous shiverer genotypes at several ages spanning postnatal development. In wild-type brains the accumulation of total transcripts as well as mature mRNA, and the transcription rate, all follow the same general pattern of rising sharply from a low level at birth to a peak at 20 days, and continuing at a somewhat reduced level into adulthood. Thus a major factor in the developmental regulation of myelin basic protein expression is the control of transcription rate. The shiverer mutation consists of a deletion of the 3' end of the myelin basic protein gene which completely prevents production of mature mRNA and protein, and results in severe dysmyelination and a trembling behavior. In shiverer brains, the transcription rates for the intact 5' end of the gene follow closely those seen in wild-type animals up to the age at which maximal myelination normally occurs. Total myelin basic protein transcripts follow a similar profile but at less than 5% the level seen in wild-type, and, as expected, no mature mRNA is detected. Thus the shiverer deletion does not remove information required for efficient, developmentally regulated transcription, and the low level of myelin basic protein gene transcripts in this mutant must be a result of their reduced stability. A higher than normal myelin basic protein gene transcription rate in older shiverer animals raises interesting questions regarding the regulatory mechanisms controlling myelinogenesis.