We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

The aim of this study was to explore neonatal nurses’and mothers of preterm infants’experiences of daily challenges. Interviews took place asking for good, bad and challenging experiences. Data were analysed using qualitative content analysis and findings were clustered in two categories: good and challenging experiences, each containing three themes. The good experiences were: managing with success as a nurse, small things matter for mothers, and a good day anyhow for mothers and nurses. The challenging experiences were: mothering in public, being (...) pulled between responsibilities, and adverse things stick under the nurses’skin. The study shows that small daily clinical matters become big issues and could lead to moral distress, and that nurses integrate ethics of justice and ethics of care while mothers are concerned about health and well-being of their specific infant only. The challenge for nursing to integrate fairness and sensitive care in family-oriented neonatal care is discussed. (shrink)

The aim of the present investigation was to describe and to classify significant ethical problems encountered by the members of the staff during the daily clinical work at a hospital medical department. A set of definitions was prepared for the purpose, including the definition of a 'significant ethical problem'. During a three month period 426 inpatients and 173 outpatients were admitted. Significant ethical problems were encountered during the management of 106 in-patients (25 per cent) and 9 out-patients (5 per cent). (...) No significant difference was found between the frequency of ethical problems in female and male patients, but a positive correlation was noted between the number of problems and the patients' age. The problem types were classified according to a problem list. The results of this investigation suggest that greater attention must be paid to discussions about ethical problems among doctors and other categories of health personnel and that, among others, medical students ought to be taught the analysis of ethical problems. (shrink)

The development of the typical cladomothallus of the red algae Antithaminion plumula (Ellis) Le Jolis [= Pterothamnion plumula (Ellis) Nägcli], (Rhodophyceae, Ceramiales) is simulated with the help of a formal language called L-systems. Two types of uniseriate filaments are distinguished: axial filaments of cladomes with indefinite growth and branching and pleuridia with definite growth and branching. The rythmical acropetal formation of secondary axes with basitonic arrangement contrasts with the intercalary basitonic formation of pleuridia, resulting in an acrotonic arrangement within an (...) axial segment. Five types of cells and two types of cell divisions intervene in the system. In addition, for the graphical representations, some morphological particularities of A. plumula are taken into account: the curvature of axial filaments, the extension of growth zones, variable cell generation times, and segment length variability along an axis. The incidence of these variables on the generated thallus form is emphasized, pointing to the singularities of A. plumula. (shrink)

The Peanese convention for the use of dots as brackets has the disadvantage that it gives only an awkward method for representing chains of indefinite length, such as the compound implicationSuch chains occur frequently in logical investigations of a metatheoretic nature, and it is convenient to have a systematic method of abbreviating them. The most obvious method of doing this would be to leave the parentheses out entirely, and to understand that in such cases the implication sign or other operation (...) appearing on the extreme left is the most inclusive; but this method, which has been followed by Quine, is at variance with our ordinary algebraic usage, in which we write a − b + c − d for ((a − b) + c) − d, and consequently leads to confusion. It is desirable to have a modification of the Peanese convention which gives a simple method of representing such chain implications, and at the same time avoids this difficulty.Such a modification is easily obtained by generalizing somewhat a procedure of Church. The latter author uses only a single dot, which he writes on the right of an operator to signify a bracket extending from that point to the end of the formula (or parenthesized expression). If dots are used only on the right of operations this is all that can be desired. But the essential idea of this device can be extended to the case where dots are used also on the left, as follows: let us suppose that a group of dots on the right of an operation or prefix denotes the beginning of a bracket which extends to the right until it meets a group with an equal or larger number of dots on the left of an operation; and that the scope of a group of dots on the left of an operation shall extend to the left until it reaches a larger group of dots on the right of some operation. (shrink)

Background Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents’ view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. Objective To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese (...) parents. Methods A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0–3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. Results Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an “opt-out” approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. Conclusion Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks. (shrink)

Background: The factors influencing parents’ willingness to enroll their children in biobanks are poorly understood. This study sought to assess parents’ willingness to enroll their children, and their perceived benefits, concerns, and information needs under different consent and data-sharing scenarios, and to identify factors associated with willingness. Methods: This large, experimental survey of patients at the 11 eMERGE Network sites used a disproportionate stratified sampling scheme to enrich the sample with historically underrepresented groups. Participants were randomized to receive one of (...) three consent and data-sharing scenarios. Results: In total, 90,000 surveys were mailed and 13,000 individuals responded (15.8% response rate). 5737 respondents were parents of minor children. Overall, 55% (95% confidence interval 50–59%) of parents were willing to enroll their youngest minor child in a hypothetical biobank; willingness did not differ between consent and data-sharing scenarios. Lower educational attainment, higher religiosity, lower trust, worries about privacy, and attitudes about benefits, concerns, and information needs were independently associated with less willingness to allow their child to participate. Of parents who were willing to participate themselves, 25% were not willing to allow their child to participate. Being willing to participate but not willing to allow one’s child to participate was independently associated with multiple factors, including race, lower educational attainment, lower annual household income, public health care insurance, and higher religiosity. Conclusions: Fifty-five percent of parents were willing to allow their youngest minor child to participate in a hypothetical biobank. Building trust, protecting privacy, and addressing attitudes may increase enrollment and diversity in pediatric biobanks. (shrink)

In this paper, the Helmholtz equation with quadratic damping themes is used for modeling the dynamics of a simple prey-predator system also called a simple Lotka–Volterra system. From the Helmholtz equation with quadratic damping themes obtained after modeling, the equilibrium points have been found, and their stability has been analyzed. Subsequently, the harmonic oscillations have been studied by the harmonic balance method, and the phenomena of resonance and hysteresis are observed. The primary and secondary resonances have been researched by the (...) multiple-scale method, and the conditions of stability of the amplitudes of oscillations are determined. Chaos is detected analytically by the Melnikov method and numerically using the basin of attraction, the bifurcation diagram, the Lyapunov exponent, the phase portrait, and the Poincaré section. The effects of all the parameters of the system are analyzed in detail, and special emphasis is placed on the new parameters. Through this analysis, the complex phenomena such as hysteresis, bistability, amplitude jump, resonances, and chaos have been obtained. The control of the parameters and the necessary conditions to control the aforementioned phenomena have been found. (shrink)

Shortages of new therapeutics to treat coronavirus disease (COVID-19) have forced clinicians, public health officials, and health systems to grapple with difficult questions about how to fairly allocate potentially life-saving treatments when there are not enough for all patients in need (1). Shortages have occurred with remdesivir, tocilizumab, monoclonal antibodies, and the oral antiviral Paxlovid (2) -/- Ensuring equitable allocation is especially important in light of the disproportionate burden experienced during the COVID-19 pandemic by disadvantaged groups, including Black, Hispanic/Latino and (...) Indigenous communities, individuals with certain disabilities, and low-income persons. However, many health systems have resorted to first-come, first-served approaches to allocation, which tend to disadvantage individuals with barriers in access to care (3). There is mounting evidence of racial, ethnic, and socioeconomic disparities in access to medications for COVID-19 (4, 5). -/- One potential method to promote equitable allocation is to use a weighted lottery, which is an allocation strategy that gives all eligible patients a chance to receive the scarce treatment while also allowing the assignment of higher or lower chances according to other ethical considerations (6). We sought to assess the feasibility of implementing a weighted lottery to allocate scarce COVID-19 medications in a large U.S. health system and to determine whether the weighted lottery promotes equitable allocation. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)