38 research outputs found
Putting Equity Back in Reverse Mortgages: Helping Seniors Retire with Dignity
Policymakers can help some seniors age in place through policies to strengthen private-sector reverse mortgages. In reverse mortgages, individuals who may be âhouse rich but cash poorâ can use their homeâs equity to receive regular income or get money through a credit line. Andrew Helman argues that state legislatures can help seniors avoid the âtricks and trapsâ of reverse mortgages by estabÂlishing programs in which lenders who agree to play by rules that ensure the safety and security of such mortgages are placed on a âpreferredâ list for seniors seeking a loan. He observes that laying the groundwork now can help a larger group of seniors age with dignity
Antibody-free magnetic cell sorting of genetically modified primary human CD4+ T cells by one-step streptavidin affinity purification.
Existing methods for phenotypic selection of genetically modified mammalian cells suffer disadvantages of time, cost and scalability and, where antibodies are used to bind exogenous cell surface markers for magnetic selection, typically yield cells coated with antibody-antigen complexes and beads. To overcome these limitations we have developed a method termed Antibody-Free Magnetic Cell Sorting in which the 38 amino acid Streptavidin Binding Peptide (SBP) is displayed at the cell surface by the truncated Low Affinity Nerve Growth Receptor (LNGFRF) and used as an affinity tag for one-step selection with streptavidin-conjugated magnetic beads. Cells are released through competition with the naturally occurring vitamin biotin, free of either beads or antibody-antigen complexes and ready for culture or use in downstream applications. Antibody-Free Magnetic Cell Sorting is a rapid, cost-effective, scalable method of magnetic selection applicable to either viral transduction or transient transfection of cell lines or primary cells. We have optimised the system for enrichment of primary human CD4+ T cells expressing shRNAs and exogenous genes of interest to purities of >99%, and used it to isolate cells following Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing
Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin
Recent genomic analyses of pathologically-defined tumor types identify âwithin-a-tissueâ disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies
Racism, Juries, and Justice: Addressing Post-Verdict Juror Testimony of Racial Prejudice During Deliberations
From the beginning, race played a role in the prosecution of Christopher McCowen for the rape and murder of well-known fashion writer Christa Worthington. To some, the trial was even a spectacle and treated as âone of the most spectacular homicide cases in [Massachusetts\u27] history.â It quickly became a âmade-for-cable-news tale of the heiress fashion writer and her lowly Portuguese fisherman lover, illicit sex, and an out-of-wedlock child,â all set in a seaside village. McCowen, an African-American garbage man, was right in the middle of it; police and prosecutors did not believe his assertions that he had consensual sex with Worthington and that someone else killed her. And after eight days of deliberations, it appeared that jurors also did not believe McCowen\u27s defense. They convicted him of Worthington\u27s rape and murder. Arguably, for some legal experts and scholars, that is where the story started to get more interesting. A few days after the deliberations, three jurors contacted McCowen\u27s lawyer and said that racial prejudice tainted the deliberations and that at least one juror felt pressure to convict. The three jurors alleged that a white juror âused the term âblack manâ in a racist manner,â that another white juror âtold fellow jurors she feared McCowen because he was a black man staring at her,â and that a Cape Verdean juror said âblacks had a tendency toward violence.â Based on the jurors\u27 affidavits, McCowen\u27s lawyer filed a motion for a new trial, arguing, among other things, that racial prejudice denied McCowen a fair trial. Similar to Maine and the federal courts, Massachusetts\u27 evidentiary guidelines bar jury testimony to impeach a verdict, except for evidence of extraneous prejudicial information or outside influences. There is disagreement among courts and scholars as to whether evidence of racial prejudice during deliberations is considered to be barred by the rule, within an exception to the rule, or whether racially prejudiced statements present constitutional problems to which the rule must give way. In Massachusetts, however, juror testimony to prove that racial prejudice tainted deliberations is allowed because doing otherwise âmight well offend fundamental fairness.â In practice, however, only a few jurors had ever been recalled at one time. In contrast to Massachusetts, the Tenth Circuit does not allow jurors to testify to show whether racial prejudice infected deliberations, though that does not mean deliberations are free from racial prejudice. Here in Maine, the law on juror testimony is not entirely clear. Trial courts have ample authority to allow post-verdict juror testimony in some instances, but the right case has not yet emerged to test the law on testimony to prove racial prejudice tainted deliberations. Accordingly, this article will explore whether the rule pits process values against notions of fairness; whether Maine trial judges have the authority to admit juror testimony in some instances; and whether it is possible to do so without undermining important process values, both before and after the verdict
Judicial Performance and Policy Implications in Moore v. Abbott
In Moore v. Abbott, a divided Maine Supreme Judicial Court, sitting as the Law Court, held that a three-member panel organized by the Attorney General to investigate alleged misconduct by prosecutors and law enforcement officers did not constitute an agency or public official under Maine\u27s Freedom of Access Act (FOAA). Therefore, the panel did not have to release records compiled during its review of the investigation and prosecution of Dennis Dechaine, who was convicted for the 1988 murder of Sarah Cherry. Justice Alexander, writing for the majority, applied a four-part test looking to whether the panel was the functional equivalent of a government agency and concluded that it was not, which meant its records could be kept confidential. Justice Levy, joined in his dissent by Justice Mead, characterized the facts differently and applied a broader version of the functional equivalency test to reach the opposite conclusion: the panel was acting as the functional equivalent of a government agency. However, Justice Levy\u27s dissent did not go so far as to assert that the records should be public; rather, he concluded that the panel acted as an agency under the FOAA, but that further analysis must be done to determine whether other statutory provisions prevent disclosure. There are several issues in the Moore decision. Most significantly, the majority opinion undermined the Maine Legislature\u27s policy favoring disclosure of government records. The Law Court previously noted that the FOAA\u27s purpose is to open public proceedings and require that public actions and records be available to the public, a result not achieved here. Additionally, the majority and dissenting opinions did not share the same understanding of the historical facts. For example, it is unclear from the majority and dissenting opinions whether the panel had access to the entire Dechaine file, including photographs of the victim designated confidential by the Maine Legislature, or whether it only had access to portions already available for public inspection. Consequently, the majority and dissenting opinions turned to different versions of the law; the majority adhered to a narrow view of the functional equivalency test, while the dissent applied a broader version that is in sync with the way several other jurisdictions supplement their freedom of access laws. Ultimately, the dissent\u27s analysis better effectuated the legislature\u27s policy of openness; therefore, the Law Court should adopt that policy in the future
A Nutrient-Sensing Transition at Birth Triggers Glucose-Responsive Insulin Secretion
A drastic transition at birth, from constant maternal nutrient supply in utero to intermittent postnatal feeding, requires changes in the metabolic system of the neonate. Despite their central role in metabolic homeostasis, little is known about how pancreatic β cells adjust to the new nutritional challenge. Here, we find that after birth β cell function shifts from amino acid- to glucose-stimulated insulin secretion in correlation with the change in the nutritional environment. This adaptation is mediated by a transition in nutrient sensitivity of the mTORC1 pathway, which leads to intermittent mTORC1 activity. Disrupting nutrient sensitivity of mTORC1 in mature β cells reverts insulin secretion to a functionally immature state. Finally, manipulating nutrient sensitivity of mTORC1 in stem cell-derived β cells in vitro strongly enhances their glucose-responsive insulin secretion. These results reveal a mechanism by which nutrients regulate β cell function, thereby enabling a metabolic adaptation for the newborn
Developmental care pathway for hospitalised infants with CHD: On behalf of the Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative
Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease, includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework