Ecological Studies of Wolves on Isle Royale, 1984-1985

Annual Report 1984-1985 (Covering the twenty-seventh year of research)https://digitalcommons.mtu.edu/wolf-annualreports/1036/thumbnail.jp

Metabotropic Glutamate Receptors as Novel Therapeutic Targets on Visceral Sensory Pathways

Metabotropic glutamate receptors (mGluR) have a diverse range of structures and molecular coupling mechanisms. There are eight mGluR subtypes divided into three major groups. Group I (mGluR1 and 5) is excitatory; groups II (mGluR2 and 3) and III (mGluR 4, 6, and 7) are inhibitory. All mGluR are found in the mammalian nervous system but some are absent from sensory neurons. The focus here is on mGluR in sensory pathways from the viscera, where they have been explored as therapeutic targets. Group I mGluR are activated by endogenous glutamate or constitutively active without agonist. Constitutive activity can be exploited by inverse agonists to reduce neuronal excitability without synaptic input. This is promising for reducing activation of nociceptive afferents and pain using mGluR5 negative allosteric modulators. Many inhibitory mGluR are also expressed in visceral afferents, many of which markedly reduce excitability. Their role in visceral pain remains to be determined, but they have shown promise in inhibition of the triggering of gastro-esophageal reflux, via an action on mechanosensory gastric afferents. The extent of reflux inhibition is limited, however, and may not reach a clinically useful level. On the other hand, negative modulation of mGluR5 has very potent actions on reflux inhibition, which has produced the most likely candidates so far as therapeutic drugs. These act probably outside the central nervous system, and may therefore provide a generous therapeutic window. There are many unanswered questions about mGluR along visceral afferent pathways, the answers to which may reveal many more therapeutic candidates

Ecological Studies of Wolves on Isle Royale, 1983-1984

Annual Report 1983-1984 (Covering the twenty-sixth year of research)https://digitalcommons.mtu.edu/wolf-annualreports/1037/thumbnail.jp

Community next steps for making globally unique identifiers work for biocollections data

Biodiversity data is being digitized and made available online at a rapidly increasing rate but current practices typically do not preserve linkages between these data, which impedes interoperation, provenance tracking, and assembly of larger datasets. For data associated with biocollections, the biodiversity community has long recognized that an essential part of establishing and preserving linkages is to apply globally unique identifiers at the point when data are generated in the field and to persist these identifiers downstream, but this is seldom implemented in practice. There has neither been coalescence towards one single identifier solution (as in some other domains), nor even a set of recommended best practices and standards to support multiple identifier schemes sharing consistent responses. In order to further progress towards a broader community consensus, a group of biocollections and informatics experts assembled in Stockholm in October 2014 to discuss community next steps to overcome current roadblocks. The workshop participants divided into four groups focusing on: identifier practice in current field biocollections; identifier application for legacy biocollections; identifiers as applied to biodiversity data records as they are published and made available in semantically marked-up publications; and cross-cutting identifier solutions that bridge across these domains. The main outcome was consensus on key issues, including recognition of differences between legacy and new biocollections processes, the need for identifier metadata profiles that can report information on identifier persistence missions, and the unambiguous indication of the type of object associated with the identifier. Current identifier characteristics are also summarized, and an overview of available schemes and practices is provided

Ecological Studies of Wolves on Isle Royale, 1982-1983

Annual Report 1982-1983 (Covering the twenty-fifth year of research)https://digitalcommons.mtu.edu/wolf-annualreports/1038/thumbnail.jp

Performance, Politics and Media: How the 2010 British General Election leadership debates generated ‘talk’ amongst the electorate.

During the British General Election 2010 a major innovation was introduced in part to improve engagement: a series of three live televised leadership debates took place where the leader of each of the three main parties, Labour, Liberal Democrat and Conservative, answered questions posed by members of the public and subsequently debated issues pertinent to the questions. In this study we consider these potentially ground breaking debates as the kind of event that was likely to generate discussion. We investigate various aspects of the ‘talk’ that emerged as a result of watching the debates. As an exploratory study concerned with situated accounts of the participants experiences we take an interpretive perspective. In this paper we outline the meta-narratives (of talk) associated with the viewing of the leadership debates that were identified, concluding our analysis by suggesting that putting a live debate on television and promoting and positioning it as a major innovation is likely to mean that is how the audience will make sense of it – as a media event

Comparison of Outcomes Following a Switch from a Brand to an Authorized vs. Independent Generic Drug

Authorized generics are identical in formulation to brand drugs, manufactured by the brand company but marketed as a generic. Generics, marketed by generic manufacturers, are required to demonstrate pharmaceutical and bioequivalence to the brand drug, but repetition of clinical trials is not required. This retrospective cohort study compared outcomes for generics and authorized generics, which serves as a generic vs. brand proxy that minimizes bias against generics. For the seven drugs studied between 1999-2014, 5,234 unique patients were on brand drug prior to generic entry and 4,900 (93.6%) switched to a generic. During the 12-months following the brand-to-generic switch, patients using generics vs. authorized generics were similar in terms of outpatient visits, urgent care visits, hospitalizations, and medication discontinuation. The likelihood of emergency department visits was slightly higher for authorized generics compared with generics. These data suggest that generics were clinically no worse than their proxy brand comparator

Primary hemiarthroplasty for treatment of proximal humeral fractures

Background: Primary hemiarthroplasty of the shoulder is used to treat complex proximal humeral fractures, although the reported functional results following this method of treatment have varied widely. The aim of this study was to prospectively assess the prosthetic survival and functional outcomes in a large series of patients treated with shoulder hemiarthroplasty for a proximal humeral fracture. By determining the factors that affected the outcome, we also aimed to produce models that could be used clinically to estimate the functional outcome at one year following surgery.Methods: A thirteen-year observational cohort study of 163 consecutive patients treated with hemiarthroplasty for a proximal humeral fracture was performed. Twenty-five patients died or were lost to follow-up in the first year after treatment, leaving 138 patients who had assessment of shoulder function with use of the modified Constant score at one year postinjury.Results: The overall rate of prosthetic survival was 96.9% at one year, 95.3% at five years, and 93.9% at ten years. The overall median modified Constant score was 64 points at one year, with a typically good score for pain relief (median, 15 points) and poorer scores, with a greater scatter of values, for function (median, 12 points), range of motion (median, 24 points), and muscle power (median, 14 points). Of the factors that were assessed immediately after the injury, only patient age, the presence of a neurological deficit, tobacco usage, and alcohol consumption were significantly predictive of the one-year Constant score (p &lt; 0.05). Of the factors that were assessed at six weeks postinjury, those that predicted the one-year Constant score included the age of the patient, the presence of a persistent neurological deficit, the need for an early reoperation, the degree of displacement of the prosthetic head from the central axis of the glenoid seen radiographically, and the degree of displacement of the tuberosities seen radiographically.Conclusions: Primary shoulder hemiarthroplasty performed for the treatment of a proximal humeral fracture in medically fit and cooperative adults is associated with satisfactory prosthetic survival at an average of 6.3 years. Although the shoulder is usually free of pain following this procedure, the overall functional result, in terms of range of motion, function, and power, at one year varies. A good functional outcome can be anticipated for a younger individual who has no preoperative neurological deficit, no postoperative complications, and a satisfactory radiographic appearance of the shoulder at six weeks. The results are poorer in the larger group of elderly patients who undergo this procedure, especially if they have a neurological deficit, a postoperative complication requiring a reoperation, or an eccentrically located prosthesis with retracted tuberosities.<br /

A Novel Approach to Contamination Suppression in Transmission Detectors for Radiotherapy

The current trend in X-ray radiotherapy is to treat cancers that are in difficult locations in the body using beams with a complex intensity profile. Intensity Modulated Radiotherapy (IMRT) is a treatment which improves the dose distribution to the tumour whilst reducing the dose to healthy tissue. Such treatments administer a larger dose per treatment fraction and hence require more complex methods to verify the accuracy of the treatment delivery. Measuring beam intensity fluctuations is difficult as the beam is heavily distorted after leaving thepatient and transmission detectors will attenuate the beam and change the energy spectrum of the beam. Monolithic Active Pixel Sensors (MAPS) are ideal solid-state detectors to measure the 2D beam profile of a radiotherapy beam upstream of the patient. MAPS sensors can be made very thin (∼ 30 μm) with still very good signal-to-noise performance. This means that the beam would pass through the sensor virtually undisturbed(< 1% attenuation). Pixel pitches of between 2 μm to 100 μm are commercially available. Large area devices (∼ 15 × 15 cm 2 ) have been produced. MAPS can be made radiation hard enough to befully functional after a large number of fractions. All this makes MAPS a very realistic transmission detector candidate for beam monitoring upstream of the patient. A remaining challenge for thin, upstream sensors is that the detectors are sensitive to the signal of both therapeutic photons and electron contamination. Here a method is presented to distinguish between the signal due to electrons and photons and thus provide real-time dosimetric information in very thin sensors that does not require Monte Carlo simulation of each linear accelerator treatment head