Molecular and Cytogenetic Characterization of de novo Acrocentric Rearrangements in Humans

I have studied 26 children who have a de novo rearrangement of the acrocentric chromosomes in order to understand the formation of these aberrations. The families include \u2725 probands ascertained for Robertsonian-type translocations, 13 between nonhomologous chromosomes and 12 between homologs, and one rea(21;21)(q22;q22). The parental origins of the de novo rearrangements were determined in 26/26 families using QFQ and NOR variants and/or RFLP analyses. While there was no overall difference in the sex distribution of the parents of origin, there were more maternally derived nonhomologous ( true Robertsonian) translocations (8 mat: 5 pat) and more paternally derived homologous rearrangements (4 mat: 9 pat). A role of the NOR in de novo formation of acrocentric rearrangements was suggested by a significantly higher incidence of dNOR variants in the parents in whom the rearrangements originated (11/26) as compared to their normal spouses (1/26) and a control population (5/50) (p\u3c0.0001). The dNOR variant was found both in parents in whom de novo Robertsonian.translocations and homologous rearrangements had occurred. Additionally, both the parents in whom rearrangements originated and their spouses had significantly higher NOR scores than the controls. This suggests that higher NOR scores in the parents may have contributed to the survival of their offspring with de novo acrocentric rearrangements since these rearrangements generally resulted in the loss of two NORs. However, compensation in NOR scores or satellite associations was not evident in these probands. RFLP analysis of rearrangements between homologous chromosomes resulting in secondary trisomy in 8 cases suggested that these rearrangements were isochromosomes, derived from one parental chromosome. Four of the homologous rearrangements were dicentric suggesting that these rearrangements may have resulted from U-type exchanges in the NOR or short arm

CT Imaging of a Pancreatic Pseudocyst: Clinical and Anatomic Implications

AbstractWe report the case of a 42-year-old man with a large pancreatic pseudocyst, the presence of which was not suspected upon initial presentation. This case provides an example of when imaging may be useful for the detection of pancreatitis and its complications. It also demonstrates classic pseudocyst localization to the lesser sac and left anterior pararenal space. The unusually large size of this pseudocyst provides a clear delineation of retroperitoneal fascial planes and an illustration of possible clinical consequences of mechanical obstruction by pseudocyst

The Evolution of Satellite III DNA Subfamilies among Primates

We demonstrate that satellite III (SatIII) DNA subfamilies cloned from human acrocentric chromosomes arose in the Hominoidea superfamily. Two groups, distinguished by sequence composition, evolved nonconcurrently, with group 2 evolving 16–23 million years ago (MYA) and the more recent group 1 sequences emerging ∼4.5 MYA. We also show the relative order of emergence of each group 2 subfamily in the various primate species. Our results show that each SatIII subfamily is an independent evolutionary unit, that the rate of evolution is not uniform between species, and that the evolution within a species is not uniform between chromosomes

Test, Trace, and Isolate: Covid-19 and the Canadian Constitution

Contact tracing is essential to controlling the spread of infectious disease and plays a central role in plans to safely loosen Covid-19 physical distancing measures and begin to reopen the economy. Contact tracing apps, used in conjunction with established human contact tracing methods, could serve as part of Canada’s “test, trace, and isolate” strategy. In this brief, we consider the potential benefits of using contract tracing apps to identify people who have been exposed to Covid-19, as well as the limitations of using this technology. We also consider the privacy implications of different app design choices. Finally, we consider how the privacy impacts of contact tracing apps could be evaluated under the Canadian Charter of Rights and Freedoms, which provides a framework for balancing competing rights and interests. We argue that so long as apps are carefully constructed and the information they reveal is appropriately safeguarded, tracing apps may have a role to play in the response of a free and democratic society to the Covid 19 pandemic. 1. Improving the Efficiency of Human Contact Tracing: The public health goal of a contact tracing app should be to integrate with human contact tracing and make it more efficient rather than replace it. We need to keep humans in the loop to ensure accuracy and to maintain the important social functions of contact tracing, which includes educating people about risks and helping them access social supports. 2. Privacy Choices: Currently, the most privacy-protective design for contact tracing apps makes use of proximity data (via Bluetooth) through a decentralized design. This method is receiving significant technical support from Apple and Google. However, this method fails to integrate with the human contact tracing system. Other options, such as the use of location logs or a centralized registration system, are more aligned with the public health goal of integration with human contact tracing but raise additional privacy questions. In addition to the constitutional questions raised by these privacy choices, there are two important considerations. First, social trust is important. If individuals do not feel comfortable with using a particular contact tracing app there will not be the large-scale uptake needed to make these an effective addition to human contact tracing. Second, due to various technical challenges, it is difficult to make effective contact tracing apps utilizing proximity data unless one uses the method supported by Apple and Google. However, Google and Apple prohibit app developers both from utilizing centralized methods and from utilizing location data. 3. Constitutional Balancing: Our privacy commissioners have discussed the need to assess these privacy choices according to the principles of necessity and proportionality. The Canadian Charter provides an important framework for thinking about these principles as it provides us with a framework for how to balance rights and interests in a free and democratic society. The Charter requires that we choose the most privacy-protective app design that meets the public health goal, so long as the benefits of meeting this goal outweigh its deleterious effects on privacy. This requires a reasonable belief in the efficacy of such an app. It also requires an assessment of the nature of the benefits, which are not just the economic benefits of reopening the economy. The currently prevailing restrictions on movement and work are themselves limitations of basic rights and liberties. Individuals who self-isolate in situations of poverty, precarious housing, mental health challenges, abusive relationships, or other vulnerabilities face challenges that affect their security of the person. There are also broader effects on equality and human flourishing. If contact tracing, enhanced by an app, reduces the need for restrictions in the form of self-isolation, it promotes other Charter rights and values (e.g., security of the person) which must be balanced against the potential infringement of privacy rights

The Common Sense of Counseling Psychology: Introducing

The goal of therapy is typically to improve clients’ self-management of their problems, not only during the course of therapy but also after therapy ends. Although it seems obvious that therapists are interested in improving client’s self-management, the psychotherapy literature has little to say on the topic. This article introduces Leventhal’s Common-Sense Model of Self-Regulation, a theoretical model of the self-management of health, and applies the model to the therapeutic process. The Common-Sense Model proposes that people develop illness representations of health threats and these illness representations guide self-management. The model has primarily been used to understand how people self-manage physical health problems, we propose it may also be useful to understand self-management of mental health problems. The Common-Sense Model’s strengths-based perspective is a natural fit for the work of counseling psychologists. In particular, the model has important practical implicationsfor addressing how clients understand mental health problems over the course of treatment and self-manage these problems during and after treatment

The effects of sildenafil on ciliary beat frequency in patients with pulmonary non-tuberculous mycobacteria disease: phase I/II trial.

RATIONALE:Pulmonary non-tuberculous mycobacterial (PNTM) disease has increased over the past several decades, especially in older women. Abnormal mucociliary clearance and abnormal nasal nitric oxide (nNO) have been associated with PNTM disease in other patient cohorts. Mucociliary clearance can be affected by NO-cyclic guanosine monophosphate signalling and, therefore, modulation of the pathway may be possible with phosphodiesterase inhibitors such as sildenafil as a novel therapeutic approach. OBJECTIVE:To define ex vivo characteristics of PNTM disease affected by sildenafil. METHODS:Subjects with PNTM infections were recruited into an open-label dose-escalation trial of sildenafil. Laboratory measurements and mucociliary measurements-ciliary beat frequency, nNO and 24-hour sputum production-were collected throughout the study period. Patients received sildenafil daily during the study period, with escalation from 20 to 40 mg three times per day. MEASUREMENTS AND MAIN RESULTS:Increased ciliary beat frequency occurred after a single dose of 40 mg sildenafil and after extended dosing of 40 mg sildenafil. The increase ciliary beat frequency was not seen with 20 mg sildenafil dosing. There were no changes in sputum production, nNO production, Quality of Life-Bronchiectasis-NTM module (QOL-B-NTM) questionnaire or the St George's Respiratory Questionnaire during the study period. CONCLUSION:Sildenafil, 40 mg, increased ciliary beat frequency acutely as well as with extended administration

Collections Of Trauma: Exploring Generative Frictions

Through this paper we identify systemic challenges that face efforts to ethically steward collections of trauma in a conflict-ridden world. Our scholarly reflections are grounded in the context of a centre being created to hold materials related to Canada’s ongoing Truth and Reconciliation Commission. We report on initial discussions with those involved in the Centre’s development and our ongoing review of court documents and media accounts related to the Centre. We call attention to the amalgamation of socio-technical, political, and legal structures that influence the actions of those managing collections of trauma. We highlight how those involved in the Centre’s development (including the researchers) are participants in and descendants of Canada’s legacy of colonizing initiatives. We identify generative frictions related to issues of conflict, plurality, agency, and distrust that underlie the design and management of collections of trauma. These reflections guide our ongoing investigation.ye