Aging Prisoners: A Brief Report of Key Legal and Policy Dilemmas

Background: The social phenomenon of the aging of the prison population has raised various legal and policy challenges. Objective: The goal of this brief report is to describe the current key legal-policy dilemmas in this field. Methods: A computerized search for legal documents, articles and studies using relevant key words was conducted in computerized databases. Results: Five key dilemmas were found: (1) Early and compassionate release of older prisoners; (2) Segregation or integration of older prisoners; (3) Heaven or hell? The meaning of imprisonment in old age; (4) Fixed v. tailored sentences to older offenders; and (5) Is prison the right place to send older offenders? Conclusion: Evidence regarding the unique socio-medical needs of older prisoners does not provide easy or simple answers to the legal-policy dilemmas in this field. Hence, as of today, the scholarly discussions in this field seem to be more normative (what "should" be the solution) rather than empirical (what "is" the evidence-based solution). Therefore, more empirical evidence is needed in order to design old-age based legal-policies towards older prisoners

High-Density Microwell Chip for Culture and Analysis of Stem Cells

With recent findings on the role of reprogramming factors on stem cells, in vitro screening assays for studying (de)-differentiation is of great interest. We developed a miniaturized stem cell screening chip that is easily accessible and provides means of rapidly studying thousands of individual stem/progenitor cell samples, using low reagent volumes. For example, screening of 700,000 substances would take less than two days, using this platform combined with a conventional bio-imaging system. The microwell chip has standard slide format and consists of 672 wells in total. Each well holds 500 nl, a volume small enough to drastically decrease reagent costs but large enough to allow utilization of standard laboratory equipment. Results presented here include weeklong culturing and differentiation assays of mouse embryonic stem cells, mouse adult neural stem cells, and human embryonic stem cells. The possibility to either maintain the cells as stem/progenitor cells or to study cell differentiation of stem/progenitor cells over time is demonstrated. Clonality is critical for stem cell research, and was accomplished in the microwell chips by isolation and clonal analysis of single mouse embryonic stem cells using flow cytometric cell-sorting. Protocols for practical handling of the microwell chips are presented, describing a rapid and user-friendly method for the simultaneous study of thousands of stem cell cultures in small microwells. This microwell chip has high potential for a wide range of applications, for example directed differentiation assays and screening of reprogramming factors, opening up considerable opportunities in the stem cell field

Imaging Immune Surveillance of Individual Natural Killer Cells Confined in Microwell Arrays

New markers are constantly emerging that identify smaller and smaller subpopulations of immune cells. However, there is a growing awareness that even within very small populations, there is a marked functional heterogeneity and that measurements at the population level only gives an average estimate of the behaviour of that pool of cells. New techniques to analyze single immune cells over time are needed to overcome this limitation. For that purpose, we have designed and evaluated microwell array systems made from two materials, polydimethylsiloxane (PDMS) and silicon, for high-resolution imaging of individual natural killer (NK) cell responses. Both materials were suitable for short-term studies (<4 hours) but only silicon wells allowed long-term studies (several days). Time-lapse imaging of NK cell cytotoxicity in these microwell arrays revealed that roughly 30% of the target cells died much more rapidly than the rest upon NK cell encounter. This unexpected heterogeneity may reflect either separate mechanisms of killing or different killing efficiency by individual NK cells. Furthermore, we show that high-resolution imaging of inhibitory synapse formation, defined by clustering of MHC class I at the interface between NK and target cells, is possible in these microwells. We conclude that live cell imaging of NK-target cell interactions in multi-well microstructures are possible. The technique enables novel types of assays and allow data collection at a level of resolution not previously obtained. Furthermore, due to the large number of wells that can be simultaneously imaged, new statistical information is obtained that will lead to a better understanding of the function and regulation of the immune system at the single cell level

The Genetic Basis of Hepatosplenic T-cell Lymphoma

Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets

Colorectal cancer cell line proteomes are representative of primary tumors and predict drug sensitivity

Proteomics holds promise for individualizing cancer treatment. We analyzed to what extent the proteomic landscape of human colorectal cancer (CRC) is maintained in established CRC cell lines and the utility of proteomics for predicting therapeutic responses. Proteomic and transcriptomic analyses were performed on 44 CRC cell lines, compared against primary CRCs (n=95) and normal tissues (n=60), and integrated with genomic and drug sensitivity data. Cell lines mirrored the proteomic aberrations of primary tumors, in particular for intrinsic programs. Tumor relationships of protein expression with DNA copy number aberrations and signatures of post-transcriptional regulation were recapitulated in cell lines. The 5 proteomic subtypes previously identified in tumors were represented among cell lines. Nonetheless, systematic differences between cell line and tumor proteomes were apparent, attributable to stroma, extrinsic signaling, and growth conditions. Contribution of tumor stroma obscured signatures of DNA mismatch repair identified in cell lines with a hypermutation phenotype. Global proteomic data showed improved utility for predicting both known drug-target relationships and overall drug sensitivity as compared with genomic or transcriptomic measurements. Inhibition of targetable proteins associated with drug responses further identified corresponding synergistic or antagonistic drug combinations. Our data provide evidence for CRC proteomic subtype-specific drug responses. Proteomes of established CRC cell line are representative of primary tumors. Proteomic data tend to exhibit improved prediction of drug sensitivity as compared with genomic and transcriptomic profiles. Our integrative proteogenomic analysis highlights the potential of proteome profiling to inform personalized cancer medicine

Age and ageism in the sentencing of older adults

As Canada\u27s population ages, judges will increasingly have to determine what sorts of sentences are appropriate for aged criminal offenders. This thesis sought to uncover current trends in judicial practices by asking the research questions: Does old age have an impact on a sentence? When, why, and in what way? Are these practices ageist? This thesis investigates these important questions by first comparing the sentences handed down to older adults (those aged older than 60 years) with those handed down to younger adults (those aged under 60 years) to see if old age has an impact on the duration of penal sentences. While the duration of the sentences handed down to older adults compared to younger adults are not significantly different, in many cases, judges explicitly state that old age operates as a factor that commands leniency in a sentence. Next, a qualitative analysis of the legal texts of the judgments examines when, why and in what way old age influences sentencing practices. These practices are then submitted to an age based critique. Old age impacts sentencing practices in a variety of ways, and can either increase or decrease the duration of a prison term. This paper concludes that, in most cases, judges adopt an age-neutral approach to sentencing

Age and ageism in the sentencing of older adults

As Canada's population ages, judges will increasingly have to determine what sorts of sentences are appropriate for aged criminal offenders. This thesis sought to uncover current trends in judicial practices by asking the research questions: Does old age have an impact on a sentence? When, why, and in what way? Are these practices ageist? This thesis investigates these important questions by first comparing the sentences handed down to older adults (those aged older than 60 years) with those handed down to younger adults (those aged under 60 years) to see if old age has an impact on the duration of penal sentences. While the duration of the sentences handed down to older adults compared to younger adults are not significantly different, in many cases, judges explicitly state that old age operates as a factor that commands leniency in a sentence. Next, a qualitative analysis of the legal texts of the judgments examines when, why and in what way old age influences sentencing practices. These practices are then submitted to an age based critique. Old age impacts sentencing practices in a variety of ways, and can either increase or decrease the duration of a prison term. This paper concludes that, in most cases, judges adopt an age-neutral approach to sentencing.Law, Faculty ofGraduat

Age and ageism in the sentencing of older adults

As Canada\u27s population ages, judges will increasingly have to determine what sorts of sentences are appropriate for aged criminal offenders. This thesis sought to uncover current trends in judicial practices by asking the research questions: Does old age have an impact on a sentence? When, why, and in what way? Are these practices ageist? This thesis investigates these important questions by first comparing the sentences handed down to older adults (those aged older than 60 years) with those handed down to younger adults (those aged under 60 years) to see if old age has an impact on the duration of penal sentences. While the duration of the sentences handed down to older adults compared to younger adults are not significantly different, in many cases, judges explicitly state that old age operates as a factor that commands leniency in a sentence. Next, a qualitative analysis of the legal texts of the judgments examines when, why and in what way old age influences sentencing practices. These practices are then submitted to an age based critique. Old age impacts sentencing practices in a variety of ways, and can either increase or decrease the duration of a prison term. This paper concludes that, in most cases, judges adopt an age-neutral approach to sentencing

Age and Ageism in the Assessment of Witnesses

As Canada’s population ages, an area of related concern is widespread and systemic discrimination against older adults known as ageism. Despite its importance, little is known about the ways age or ageism relate to judges’ credibility decisions in common law trials. This study empirically examines case law to see if there is a relationship between old age and judges’ credibility decisions for a sample of witnesses (N=898). T-tests and probit regressions showed a positive correlation between old age and judges’ assessments of general credibility, where witnesses aged over 60 were more likely to be positively assessed. At the same time, testimony from witnesses who were aged over 60 was also less likely to be positively assessed in terms of weight. The other evidence led by the party that called a witness was the strongest predictor of judges’ assessments. When the inquiry is shifted to the texts of individual cases, there are examples of judges holding stereotypical beliefs about older individuals who testify in their courtrooms. The final part of this dissertation moves beyond credibility decisions and considers the ways the rules of evidence and procedure could disproportionately exclude older adults from participating in trials. While the rules are capable of accommodating witnesses who experience limitations, a case law review finds that these provisions are rarely used for older adults. Through its detailed catalogue of judicial behaviours and analysis of rules and procedure, this study provides insights into the ways age and ageism could affect older witnesses, a conclusion with that has implications for research as well as for those who practice law.S.J.D