RIGHT TO COUNSEL/CRIMINAL LAW--WISHING FOR RIGHTS: INTERPRETING THE ARTICLE 12 RIGHT TO COUNSEL IN MASSACHUSETTS IN THE AFTERMATH OF MONTEJO v. LOUISIANA

This Note reviews Montejo v. Louisiana (2009) and discusses its implications on Article 12 of the Massachusetts Declaration of Rights, particularly related to post-arraignment waivers of a defendant’s right to counsel at a police-initiated interrogation. Montejo’s appeal relied upon a bright-line rule (Jackson rule) established 26 years before, which makes post-arraignment waivers of a defendant’s right to counsel at a police-initiated interrogation presumptively invalid. In Montejo, the Supreme Court did away with the Jackson rule, while allowing that a state may continue to adhere to the Jackson rule under its state constitution. The Author finds that historically the right to counsel in Massachusetts demonstrates the Commonwealth’s longstanding record of being proactive in both affording indigent criminal defendants the right to counsel before the Supreme Court and expanding the right to counsel when the Supreme Court has limited it. While Montejo has affected “a sea change in the law,” the Author argues that following the Supreme Court’s holding in Montejo would degrade the right to counsel and Massachusetts courts should continue the prohibition that is in place forbidding police-initiated interrogations of represented defendants. Further, adherence by the Massachusetts Supreme Judicial Court to pre-Montejo law would continue to provide a bright-line, workable rule thereby ensuring that the protections afforded by Article 12 do not become mere abstractions

RIGHT TO COUNSEL/CRIMINAL LAW--WISHING FOR RIGHTS: INTERPRETING THE ARTICLE 12 RIGHT TO COUNSEL IN MASSACHUSETTS IN THE AFTERMATH OF MONTEJO v. LOUISIANA

This Note reviews Montejo v. Louisiana (2009) and discusses its implications on Article 12 of the Massachusetts Declaration of Rights, particularly related to post-arraignment waivers of a defendant’s right to counsel at a police-initiated interrogation. Montejo’s appeal relied upon a bright-line rule (Jackson rule) established 26 years before, which makes post-arraignment waivers of a defendant’s right to counsel at a police-initiated interrogation presumptively invalid. In Montejo, the Supreme Court did away with the Jackson rule, while allowing that a state may continue to adhere to the Jackson rule under its state constitution. The Author finds that historically the right to counsel in Massachusetts demonstrates the Commonwealth’s longstanding record of being proactive in both affording indigent criminal defendants the right to counsel before the Supreme Court and expanding the right to counsel when the Supreme Court has limited it. While Montejo has affected “a sea change in the law,” the Author argues that following the Supreme Court’s holding in Montejo would degrade the right to counsel and Massachusetts courts should continue the prohibition that is in place forbidding police-initiated interrogations of represented defendants. Further, adherence by the Massachusetts Supreme Judicial Court to pre-Montejo law would continue to provide a bright-line, workable rule thereby ensuring that the protections afforded by Article 12 do not become mere abstractions

RIGHT TO COUNSEL/CRIMINAL LAW--WISHING FOR RIGHTS: INTERPRETING THE ARTICLE 12 RIGHT TO COUNSEL IN MASSACHUSETTS IN THE AFTERMATH OF MONTEJO v. LOUISIANA

This Note reviews Montejo v. Louisiana (2009) and discusses its implications on Article 12 of the Massachusetts Declaration of Rights, particularly related to post-arraignment waivers of a defendant’s right to counsel at a police-initiated interrogation. Montejo’s appeal relied upon a bright-line rule (Jackson rule) established 26 years before, which makes post-arraignment waivers of a defendant’s right to counsel at a police-initiated interrogation presumptively invalid. In Montejo, the Supreme Court did away with the Jackson rule, while allowing that a state may continue to adhere to the Jackson rule under its state constitution. The Author finds that historically the right to counsel in Massachusetts demonstrates the Commonwealth’s longstanding record of being proactive in both affording indigent criminal defendants the right to counsel before the Supreme Court and expanding the right to counsel when the Supreme Court has limited it. While Montejo has affected “a sea change in the law,” the Author argues that following the Supreme Court’s holding in Montejo would degrade the right to counsel and Massachusetts courts should continue the prohibition that is in place forbidding police-initiated interrogations of represented defendants. Further, adherence by the Massachusetts Supreme Judicial Court to pre-Montejo law would continue to provide a bright-line, workable rule thereby ensuring that the protections afforded by Article 12 do not become mere abstractions

RIGHT TO COUNSEL/CRIMINAL LAW--WISHING FOR RIGHTS: INTERPRETING THE ARTICLE 12 RIGHT TO COUNSEL IN MASSACHUSETTS IN THE AFTERMATH OF MONTEJO v. LOUISIANA

This Note reviews Montejo v. Louisiana (2009) and discusses its implications on Article 12 of the Massachusetts Declaration of Rights, particularly related to post-arraignment waivers of a defendant’s right to counsel at a police-initiated interrogation. Montejo’s appeal relied upon a bright-line rule (Jackson rule) established 26 years before, which makes post-arraignment waivers of a defendant’s right to counsel at a police-initiated interrogation presumptively invalid. In Montejo, the Supreme Court did away with the Jackson rule, while allowing that a state may continue to adhere to the Jackson rule under its state constitution. The Author finds that historically the right to counsel in Massachusetts demonstrates the Commonwealth’s longstanding record of being proactive in both affording indigent criminal defendants the right to counsel before the Supreme Court and expanding the right to counsel when the Supreme Court has limited it. While Montejo has affected “a sea change in the law,” the Author argues that following the Supreme Court’s holding in Montejo would degrade the right to counsel and Massachusetts courts should continue the prohibition that is in place forbidding police-initiated interrogations of represented defendants. Further, adherence by the Massachusetts Supreme Judicial Court to pre-Montejo law would continue to provide a bright-line, workable rule thereby ensuring that the protections afforded by Article 12 do not become mere abstractions

Les isoformes P1 et P2 du récepteur nucléaire HNF4α ont des fonctions différentes dans le cancer colorectal

Le récepteur nucléaire HNF4α est un facteur de transcription qui contrôle l’expression des gènes au niveau de l’épithélium de l’intestin et du côlon. Récemment associé au cancer colorectal, HNF4α pourrait réguler des processus importants pour la survie des cellules cancéreuses. Son rôle dans le cancer colorectal est toutefois controversé, ce qui compromet son utilisation en tant que cible thérapeutique. Par contre, les fonctions de HNF4α au côlon sont accomplies par deux différentes classes d’isoformes (P1 et P2) qui ont été très peu caractérisées jusqu’à présent. Pour clarifier le rôle de HNF4α, nous avons donc évalué les fonctions spécifiques de ses isoformes P1 et P2 dans le cancer colorectal. Nous avons observé que l’expression des isoformes P1 de HNF4α est localisée dans la région supérieure différenciée des cryptes du côlon alors que celle des isoformes P2 dans la région inférieure proliférative. Au cours du cancer colorectal, l’expression des isoformes P1 est inhibée au niveau de leur ARNm par l’activation de la β-caténine alors que l’expression des isoformes P2 est maintenue. Pour vérifier si ces isoformes ont des fonctions spécifiques dans le cancer colorectal, nous avons déterminé par ChIP-seq et RNA-seq leur gènes cibles spécifiques chez les Caco2/15. Les résultats suggèrent que les isoformes de HNF4α régulent des réseaux de gènes distincts permettant aux isoformes P1 d’influencer le métabolisme énergétique et aux isoformes P2 les mécanismes moléculaires associés au développement du cancer colorectal. De plus, plusieurs des partenaires protéiques des isoformes P2 identifiés par GFP-Trap et BioID chez les cellules cancéreuses sont associés aux mécanismes de réparation des dommages à l’ADN suggérant un nouveau rôle pour HNF4α. Notre étude suggère donc que les isoformes P1 et P2 de HNF4α régulent des réseaux de gènes différents dans le cancer colorectal. L’inhibition des isoformes P1 par la β-caténine pourrait permettre d’adapter le métabolisme aux besoins des cellules cancéreuses alors que le maintien de l’expression des isoformes P2, favoriser l’activité des voies oncogéniques et contribuer à la réponse aux dommages à l’ADN

Loss of Hepatocyte-Nuclear-Factor-4α Affects Colonic Ion Transport and Causes Chronic Inflammation Resembling Inflammatory Bowel Disease in Mice

BACKGROUND: Hnf4alpha, an epithelial specific transcriptional regulator, is decreased in inflammatory bowel disease and protects against chemically-induced colitis in mice. However, the precise role of this factor in maintaining normal inflammatory homeostasis of the intestine remains unclear. The aim of this study was to evaluate the sole role of epithelial Hnf4alpha in the maintenance of gut inflammatory homeostasis in mice. METHODOLOGY/PRINCIPAL FINDINGS: We show here that specific epithelial deletion of Hnf4alpha in mice causes spontaneous chronic intestinal inflammation leading to focal areas of crypt dropout, increased cytokines and chemokines secretion, immune cell infiltrates and crypt hyperplasia. A gene profiling analysis in diseased Hnf4alpha null colon confirms profound genetic changes in cell death and proliferative behaviour related to cancer. Among the genes involved in the immune protection through epithelial barrier function, we identify the ion transporter claudin-15 to be down-modulated early in the colon of Hnf4alpha mutants. This coincides with a significant decrease of mucosal ion transport but not of barrier permeability in young animals prior to the manifestation of the disease. We confirm that claudin-15 is a direct Hnf4alpha gene target in the intestinal epithelial context and is down-modulated in mouse experimental colitis and inflammatory bowel disease. CONCLUSION: Our results highlight the critical role of Hnf4alpha to maintain intestinal inflammatory homeostasis during mouse adult life and uncover a novel function for Hnf4alpha in the regulation of claudin-15 expression. This establishes Hnf4alpha as a mediator of ion epithelial transport, an important process for the maintenance of gut inflammatory homeostasis

Motivational engagement in first-time hearing aid users: a feasibility study

Objective: To assess (1) the feasibility of incorporating the Ida Institute’s Motivation Tools into a UK audiology service, (2) the potential benefits of motivational engagement in first-time hearing aid users, and (3) predictors of hearing aid and general health outcome measures. Design: A feasibility study using a single-centre, prospective, quasi-randomized controlled design with two arms. The Ida Institute’s Motivation Tools formed the basis for motivational engagement. Study sample: First-time hearing aid users were recruited at the initial hearing assessment appointment. The intervention arm underwent motivational engagement (M+, n = 32), and a control arm (M-, n = 36) received standard care only. Results: The M+ group showed greater self-efficacy, reduced anxiety, and greater engagement with the audiologist at assessment and fitting appointments. However, there were no significant between-group differences 10-weeks post-fitting. Hearing-related communication scores predicted anxiety, and social isolation scores predicted depression for the M+ group. Readiness to address hearing difficulties predicted hearing aid outcomes for the M- group. Hearing sensitivity was not a predictor of outcomes. Conclusions: There were some positive results from motivational engagement early in the patient journey. Future research should consider using qualitative methods to explore whether there are longer-term benefits of motivational engagement in hearing aid users

Nuclear Receptor HNF4α Binding Sequences are Widespread in Alu Repeats

<p>Abstract</p> <p>Background</p> <p>Alu repeats, which account for ~10% of the human genome, were originally considered to be junk DNA. Recent studies, however, suggest that they may contain transcription factor binding sites and hence possibly play a role in regulating gene expression.</p> <p>Results</p> <p>Here, we show that binding sites for a highly conserved member of the nuclear receptor superfamily of ligand-dependent transcription factors, hepatocyte nuclear factor 4alpha (HNF4α, NR2A1), are highly prevalent in Alu repeats. We employ high throughput protein binding microarrays (PBMs) to show that HNF4α binds > 66 unique sequences in Alu repeats that are present in ~1.2 million locations in the human genome. We use chromatin immunoprecipitation (ChIP) to demonstrate that HNF4α binds Alu elements in the promoters of target genes (<it>ABCC3, APOA4, APOM, ATPIF1, CANX, FEMT1A, GSTM4, IL32, IP6K2, PRLR, PRODH2, SOCS2, TTR</it>) and luciferase assays to show that at least some of those Alu elements can modulate HNF4α-mediated transactivation <it>in vivo </it>(<it>APOM, PRODH2, TTR, APOA4</it>). HNF4α-Alu elements are enriched in promoters of genes involved in RNA processing and a sizeable fraction are in regions of accessible chromatin. Comparative genomics analysis suggests that there may have been a gain in HNF4α binding sites in Alu elements during evolution and that non Alu repeats, such as Tiggers, also contain HNF4α sites.</p> <p>Conclusions</p> <p>Our findings suggest that HNF4α, in addition to regulating gene expression via high affinity binding sites, may also modulate transcription via low affinity sites in Alu repeats.</p

AUDITORY BRAINSTEM RESPONSE THRESHOLD AND DISTORTION PRODUCT OTOACOUSTIC EMISSION AMPLITUDE IN GUINEA PIGS By LORRAINE REID BABEU

xv CHAPTERS