Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors

The deafness caused by early onset hypothyroidism indicates that thyroid hormone is essential for the development of hearing. We investigated the underlying roles of the TRa1 and TRß thyroid hormone receptors in the auditory system using receptor-deficient mice. TRa1 and TRß, which act as hormone-activated transcription factors, are encoded by the Thra and Thrb genes, respectively, and both are expressed in the developing cochlea. TRß is required for hearing because TRß-deficient (Thrb tm1/tm1) mice have a defective auditory-evoked brainstem response and retarded expression of a potassium current (I K,f) in the cochlear inner hair cells. Here, we show that although TRa1 is individually dispensable, TRa1 and TRß synergistically control an extended array of functions in postnatal cochlear development. Compared with Thrb tm1/tm1 mice, the deletion of all TRs inThra tm1/tm1 Thrb tm1/tm1mice produces exacerbated and novel phenotypes, including delayed differentiation of the sensory epithelium, malformation of the tectorial membrane, impairment of electromechanical transduction in outer hair cells, and a low endocochlear potential. The induction ofI K,f in inner hair cells was not markedly more retarded than in Thrb tm1/tm1mice, suggesting that this feature of hair cell maturation is primarily TRß-dependent. These results indicate that distinct pathways mediated by TRß alone or by TRß and TRa1 together facilitate control over an extended range of functions during the maturation of the cochlea

Are "part-time" general practitioners workforce idlers or committed professionals?

BACKGROUND: The traditional view of general practice holds that only general practitioners (GPs) in full-time clinical practice can provide quality patient care. Nevertheless, increasing numbers of GPs are choosing to work sessionally, that is, ostensibly “part-time”. There are concerns about the health workforce’s ability to meet demand and also fears that patient care may be compromised. We sought answers to a) what activities do GPs undertake when not consulting patients, b) why do they choose to work sessionally, and c) does sessional general practice reflect a lack of commitment to patients and the profession? METHODS: Semi-structured interviews were conducted with GPs who worked sessionally, (i.e. six or fewer sessions a week in clinical general practice, where a session comprises four consecutive hours of patient care). These data were analysed qualitatively and saturation was reached. RESULTS: The majority of participants were in full-time paid employment, while part-time in clinical general practice. They reported that consultations increasingly required the management of patients with complex, chronic conditions who also required psychological management. Coupled with unrealistic patient expectations, these factors led GPs to be concerned about maintaining the quality patient care they considered professionally desirable. Many diversified their work activities to ensure that they retained their professional standards. CONCLUSIONS: “Part-time” general practice is a misnomer that masks the contribution these GPs make as part of the health workforce. Sessional practice more accurately describes the nature of our participants’ clinical work. Their choice of sessional work is a professional response to the increasing demands within the consultation. It enables GPs to maintain their commitment to quality patient care and their profession, while attenuating the challenges of demanding consultations. Sessional general practitioners demonstrate strong commitment to their patients and the profession

A Study of the myc Gene in Feline Leukaemias

I isolated and characterised a clone of the normal feline c-myc gene. Sequence analysis showed the gene to be highly related in other mammals but less well related in the chicken. The feline c-myc gene possessed an apparently non-coding first exon with a dual promoter structure, similar to that found in the human and mouse c-myc genes. The sequences of three independent FeLV v-myc genes were compared to that of the c-myc gene to identify possible structural alterations involved in myc oncogenic activation. The c-myc clone also provided probes to map c-myc rearrangements in feline thymic lymphosarcomas. Some rearrangements were due to FeLV integration within or upstream of c-myc, but one case involved a complex 3' alteration which was apparently not directly virus-induced. S1 nuclease mapping of RNA from normal cells using c-myc probes located 5' discontinuities to each of the two promoter-like sequences (P1 and P2), and a major 3' discontinuity mapping to the most 3' of two possible polyadenylation signals. Tumours carrying c-myc rearrangements did not display readily obvious abnormalities in the structure or levels of c-myc RNA, except for case T24 which appeared to contain RNA lacking exon 1 sequences. However, the ratio of P1 to P2 RNAs detected in tumours varied considerably and was high in tumours with a rearrangement adjacent to c-myc, although it was equally high in some tumours with an ostensibly normal c-myc gene structure. There was a consistent lack of detectable RNA from normal c-myc alleles in tumours containing different myc-transducing FeLVs. Also, in tumour T24 which expressed a rearranged c-myc gene, RNA from the normal c-myc allele could not be detected. The phenotype of thymic tumours was characterised with respect to expression of RNA of the a and beta-chains of the T-cell antigen receptor (TCR). Several tumours, including all those induced by two myc-transducing FeLVs and others carrying a rearranged c-myc gene, contained TCR a and beta-chain transcripts. This study provided preliminary evidence that one tumour contained independently transduced myc and beta-chain TCR genes present in separate FeLV proviruses, suggesting a direct role for TCR genes in oncogenesis

The Norfolk Hoax: Fear Social Violence and Ethnicity at the Norfolk Navy Yard During the Strike of 1877

This thesis examines the contributing causes why the command of the Norfolk Navy Yard feared a labor uprising or riot in the surrounding community of Portsmouth, Virginia in July 1877. Racial, class and ethnic tensions heightened to the point that on the morning of July 25, 1877, unknown agents distributed pamphlets around the city, which appealed to workers at the Navy Yard. A culture of social violence was prevalent during Norfolk and Portsmouth\u27s post-Civil War existence. The ground-level view offered by this thesis is of the intense fear that spread across the country in 1877 as a result of severe economic depression, ethnic tensions, and racial conflict. A combination of racial and labor antagonism was latent in both cities and the navy yard\u27s location, its function as federal outpost in the South, and largest employer in the area caused its commander, J. Blakeley Creighton, to take the precautionary measure of landing the fleet\u27s firepower in Portsmouth. This thesis proves that the larger context of social fear, violence, and depression that marked Reconstruction, labor unrest and naval mismanagement combined to create a culture of fear and violence at the Norfolk Navy Yard in July of 1877

TheEffects of Decision Aid Recommendations on Users’ Cognitive Processes, Memories, and Judgments

This study extends the existing decision aid literature by examining the influence of decision aid recommendations on users’ memories, decision processes, and judgments. Existing research suggests that decision aids can be beneficial in a variety of settings. Judgments or decisions, the outputs of the decision- making process, are the focus of most of the decision aid research. This study offers a more comprehensive investigation of the impact of decision aids by examining both the outputs of the decision-making process and the inputs and processes that lead to judgment and decision-making. An experiment is conducted that examines the influence of decision aid recommendations on memory patterns, search, cue usage, and judgments. Specifically, the study focuses on how positive and negative decision aid recommendations and the timing of receipt of the decision aid recommendation differentially affect these components of the decision process. The key findings of the research are: (1) decision aid recommendations create strong affective responses that are encoded in memory and cause users to reconstruct memories of financial data to be consistent with the affective response, (2) receiving a decision aid recommendation at the start of a task creates a strong initial response that acts as an initial hypothesis wherein users’ subsequent information search patterns exhibit a confirming bias, (3) receiving a decision aid recommendation later in the task creates a strong response that initiates professional skepticism and causes users’ subsequent information search patterns to exhibit a disconfirming bias, (4) decision aid recommendations influence the choice of information cues users believe to be important, (5) decision aid recommendations exert influence on users’ judgments, with the amount of influence diminishing as additional information is received, and (6) working memory capacity is a determinant in the ability to recall financial information but does not determine the extent of influence decision aid recommendations have on users. These findings, when considered together, validate the need for a more complete examination of how decision aids impact the entire decision-making process to identify potential negative consequences in addition to proposed benefits. This research demonstrates that task structure can be manipulated to mitigate certain undesirable consequences of decision aid use

Detection of Potential Transit Signals in Sixteen Quarters of Kepler Mission Data

We present the results of a search for potential transit signals in four years of photometry data acquired by the Kepler Mission. The targets of the search include 111,800 stars which were observed for the entire interval and 85,522 stars which were observed for a subset of the interval. We found that 9,743 targets contained at least one signal consistent with the signature of a transiting or eclipsing object, where the criteria for detection are periodicity of the detected transits, adequate signal-to-noise ratio, and acceptance by a number of tests which reject false positive detections. When targets that had produced a signal were searched repeatedly, an additional 6,542 signals were detected on 3,223 target stars, for a total of 16,285 potential detections. Comparison of the set of detected signals with a set of known and vetted transit events in the Kepler field of view shows that the recovery rate for these signals is 96.9%. The ensemble properties of the detected signals are reviewed.Comment: Accepted by ApJ Supplemen

Planetary Candidates Observed by Kepler IV: Planet Sample From Q1-Q8 (22 Months)

We provide updates to the Kepler planet candidate sample based upon nearly two years of high-precision photometry (i.e., Q1-Q8). From an initial list of nearly 13,400 Threshold Crossing Events (TCEs), 480 new host stars are identified from their flux time series as consistent with hosting transiting planets. Potential transit signals are subjected to further analysis using the pixel-level data, which allows background eclipsing binaries to be identified through small image position shifts during transit. We also re-evaluate Kepler Objects of Interest (KOI) 1-1609, which were identified early in the mission, using substantially more data to test for background false positives and to find additional multiple systems. Combining the new and previous KOI samples, we provide updated parameters for 2,738 Kepler planet candidates distributed across 2,017 host stars. From the combined Kepler planet candidates, 472 are new from the Q1-Q8 data examined in this study. The new Kepler planet candidates represent ~40% of the sample with Rp~1 Rearth and represent ~40% of the low equilibrium temperature (Teq<300 K) sample. We review the known biases in the current sample of Kepler planet candidates relevant to evaluating planet population statistics with the current Kepler planet candidate sample.Comment: 12 pages, 8 figures, Accepted ApJ Supplemen

Planetary Candidates Observed by Kepler V: Planet Sample from Q1-Q12 (36 Months)

The Kepler mission discovered 2842 exoplanet candidates with 2 years of data. We provide updates to the Kepler planet candidate sample based upon 3 years (Q1-Q12) of data. Through a series of tests to exclude false-positives, primarily caused by eclipsing binary stars and instrumental systematics, 855 additional planetary candidates have been discovered, bringing the total number known to 3697. We provide revised transit parameters and accompanying posterior distributions based on a Markov Chain Monte Carlo algorithm for the cumulative catalogue of Kepler Objects of Interest. There are now 130 candidates in the cumulative catalogue that receive less than twice the flux the Earth receives and more than 1100 have a radius less than 1.5 Rearth. There are now a dozen candidates meeting both criteria, roughly doubling the number of candidate Earth analogs. A majority of planetary candidates have a high probability of being bonafide planets, however, there are populations of likely false-positives. We discuss and suggest additional cuts that can be easily applied to the catalogue to produce a set of planetary candidates with good fidelity. The full catalogue is publicly available at the NASA Exoplanet Archive.Comment: Accepted for publication, ApJ