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1.  Sexual Reproduction and Seasonality of the Alaskan Red Tree Coral, Primnoa pacifica 
PLoS ONE  2014;9(4):e90893.
The red tree coral Primnoa pacifica is an important habitat forming octocoral in North Pacific waters. Given the prominence of this species in shelf and upper slope areas of the Gulf of Alaska where fishing disturbance can be high, it may be able to sustain healthy populations through adaptive reproductive processes. This study was designed to test this hypothesis, examining reproductive mode, seasonality and fecundity in both undamaged and simulated damaged colonies over the course of 16 months using a deepwater-emerged population in Tracy Arm Fjord. Females within the population developed asynchronously, though males showed trends of synchronicity, with production of immature spermatocysts heightened in December/January and maturation of gametes in the fall months. Periodicity of individuals varied from a single year reproductive event to some individuals taking more than the 16 months sampled to produce viable gametes. Multiple stages of gametes occurred in polyps of the same colony during most sampling periods. Mean oocyte size ranged from 50 to 200 µm in any season, and maximum oocyte size (802 µm) suggests a lecithotrophic larva. No brooding larvae were found during this study, though unfertilized oocytes were found adhered to the outside of polyps, where they are presumably fertilized. This species demonstrated size-dependent reproduction, with gametes first forming in colonies over 42-cm length, and steady oocyte sizes being achieved after reaching 80-cm in length. The average fecundity was 86 (±12) total oocytes per polyp, and 17 (±12) potential per polyp fecundity. Sub-lethal injury by removing 21–40% of colony tissue had no significant reproductive response in males or females over the course of this study, except for a corresponding loss in overall colony fecundity. The reproductive patterns and long gamete generation times observed in this study indicate that recruitment events are likely to be highly sporadic in this species increasing its vulnerability to anthropogenic disturbances.
PMCID: PMC4000209  PMID: 24770675
2.  Can virtual nature improve patient experiences and memories of dental treatment? A study protocol for a randomized controlled trial 
Trials  2014;15:90.
Dental anxiety and anxiety-related avoidance of dental care create significant problems for patients and the dental profession. Distraction interventions are used in daily medical practice to help patients cope with unpleasant procedures. There is evidence that exposure to natural scenery is beneficial for patients and that the use of virtual reality (VR) distraction is more effective than other distraction interventions, such as watching television. The main aim of this randomized controlled trial is to determine whether the use of VR during dental treatment can improve the overall dental experience and recollections of treatment for patients, breaking the negative cycle of memories of anxiety leading to further anxiety, and avoidance of future dental appointments. Additionally, the aim is to test whether VR benefits dental patients with all levels of dental anxiety or whether it could be especially beneficial for patients suffering from higher levels of dental anxiety. The third aim is to test whether the content of the VR distraction can make a difference for its effectiveness by comparing two types of virtual environments, a natural environment and an urban environment.
The effectiveness of VR distraction will be examined in patients 18 years or older who are scheduled to undergo dental treatment for fillings and/or extractions, with a maximum length of 30 minutes. Patients will be randomly allocated into one of three groups. The first group will be exposed to a VR of a natural environment. The second group will be exposed to a VR of an urban environment. A third group consists of patients who receive standard care (control group). Primary outcomes relate to patients’ memories of the dental treatment one week after treatment: (a) remembered pain, (b) intrusive thoughts and (c) vividness of memories. Other measures of interest are the dental experience, the treatment experience and the VR experience.
Trial registration
Current Controlled Trials ISRCTN41442806
PMCID: PMC3978097  PMID: 24655569
Dental anxiety; distraction; memories; virtual reality
3.  Enhancing Neural Transmission in Multiple Sclerosis (4-Aminopyridine Therapy) 
Neurotherapeutics  2012;10(1):106-110.
Enhancing neural transmission by improving axonal conduction and synaptic neurotransmitter release is a novel strategy to improve symptoms in multiple sclerosis. Dalfampridine (4-aminopyridine extended-release) is a first-in-class medication that targets the damaged nervous system through blockage of voltage-gated potassium channels. Through a series of clinical trials, dalfampridine (dosed at 10 mg twice daily) has been found to improve walking speed by approximately 25 % on average in one third of individuals with multiple sclerosis regardless of disease stage. Furthermore, it significantly improves patients' perception of their ambulatory disability and may improve lower extremity strength. Given the mechanism of action, the most serious adverse effect is its pro-convulsant property, which occurs more frequently at high serum concentrations. The most common adverse events include increased falls, urinary tract infections, dizziness, insomnia, and headaches. Despite these potential side-effects, the vast majority of individuals who derive benefit continue on the treatment. The exact mechanism of action is uncertain, as is the reason for response variability. The medication serves as proof-of-concept that targeting axonal transmission can improve disability in multiple sclerosis.
Electronic supplementary material
The online version of this article (doi:10.1007/s13311-012-0156-3) contains supplementary material, which is available to authorized users.
PMCID: PMC3557354  PMID: 23184313
Multiple sclerosis; Gait disorder; Potassium channel; Neural transmission; Dalfampridine
4.  Structure-Forming Corals and Sponges and Their Use as Fish Habitat in Bering Sea Submarine Canyons 
PLoS ONE  2012;7(3):e33885.
Continental margins are dynamic, heterogeneous settings that can include canyons, seamounts, and banks. Two of the largest canyons in the world, Zhemchug and Pribilof, cut into the edge of the continental shelf in the southeastern Bering Sea. Here currents and upwelling interact to produce a highly productive area, termed the Green Belt, that supports an abundance of fishes and squids as well as birds and marine mammals. We show that in some areas the floor of these canyons harbors high densities of gorgonian and pennatulacean corals and sponges, likely due to enhanced surface productivity, benthic currents and seafloor topography. Rockfishes, including the commercially important Pacific ocean perch, Sebastes alutus, were associated with corals and sponges as well as with isolated boulders. Sculpins, poachers and pleuronectid flounders were also associated with corals in Pribilof Canyon, where corals were most abundant. Fishes likely use corals and sponges as sources of vertical relief, which may harbor prey as well as provide shelter from predators. Boulders may be equivalent habitat in this regard, but are sparse in the canyons, strongly suggesting that biogenic structure is important fish habitat. Evidence of disturbance to the benthos from fishing activities was observed in these remote canyons. Bottom trawling and other benthic fishing gear has been shown to damage corals and sponges that may be very slow to recover from such disturbance. Regulation of these destructive practices is key to conservation of benthic habitats in these canyons and the ecosystem services they provide.
PMCID: PMC3309998  PMID: 22470486
5.  The (human) science of medical virtual learning environments 
The uptake of virtual simulation technologies in both military and civilian surgical contexts has been both slow and patchy. The failure of the virtual reality community in the 1990s and early 2000s to deliver affordable and accessible training systems stems not only from an obsessive quest to develop the ‘ultimate’ in so-called ‘immersive’ hardware solutions, from head-mounted displays to large-scale projection theatres, but also from a comprehensive lack of attention to the needs of the end users. While many still perceive the science of simulation to be defined by technological advances, such as computing power, specialized graphics hardware, advanced interactive controllers, displays and so on, the true science underpinning simulation—the science that helps to guarantee the transfer of skills from the simulated to the real—is that of human factors, a well-established discipline that focuses on the abilities and limitations of the end user when designing interactive systems, as opposed to the more commercially explicit components of technology. Based on three surgical simulation case studies, the importance of a human factors approach to the design of appropriate simulation content and interactive hardware for medical simulation is illustrated. The studies demonstrate that it is unnecessary to pursue real-world fidelity in all instances in order to achieve psychological fidelity—the degree to which the simulated tasks reproduce and foster knowledge, skills and behaviours that can be reliably transferred to real-world training applications.
PMCID: PMC3013422  PMID: 21149363
human factors; human-centred design; virtual environments; medical and surgical simulation; fidelity
6.  Collaborative working within UK NHS secondary care and across sectors for COPD and the impact of peer review: qualitative findings from the UK National COPD Resources and Outcomes Project 
We investigated the effects on collaborative work within the UK National Health Service (NHS) of an intervention for service quality improvement: informal, structured, reciprocated, multidisciplinary peer review with feedback and action plans. The setting was care for chronic obstructive pulmonary disease (COPD).
Theory and methods
We analysed semi-structured interviews with 43 hospital respiratory consultants, nurses and general managers at 24 intervention and 11 control sites, as part of a UK randomised controlled study, the National COPD Resources and Outcomes Project (NCROP), using Scott's conceptual framework for action (inter-organisational, intra-organisational, inter-professional and inter-individual). Three areas of care targeted by NCROP involved collaboration across primary and secondary care.
Hospital respiratory department collaborations with commissioners and hospital managers varied. Analysis suggested that this is related to team responses to barriers. Clinicians in unsuccessful collaborations told ‘atrocity stories’ of organisational, structural and professional barriers to service improvement. The others removed barriers by working with government and commissioner agendas to ensure continued involvement in patients' care. Multidisciplinary peer review facilitated collaboration between participants, enabling them to meet, reconcile differences and exchange ideas across boundaries.
The data come from the first randomised controlled trial of organisational peer review, adding to research into UK health service collaborative work, which has had a more restricted focus on inter-professional relations. NCROP peer review may only modestly improve collaboration but these data suggest it might be more effective than top-down exhortations to change when collaboration both across and within organisations is required.
PMCID: PMC2948684  PMID: 20922063
collaboration; inter-organizational; inter-professional; quality improvement; respiratory disease
7.  Introducing the national COPD resources and outcomes project 
We report baseline data on the organisation of COPD care in UK NHS hospitals participating in the National COPD Resources and Outcomes Project (NCROP).
We undertook an initial survey of participating hospitals in 2007, looking at organisation and performance indicators in relation to general aspects of care, provision of non-invasive ventilation (NIV), pulmonary rehabilitation, early discharge schemes, and oxygen. We compare, where possible, against the national 2003 audit.
100 hospitals participated. These were typically larger sized Units. Many aspects of COPD care had improved since 2003. Areas for further improvement include organisation of acute care, staff training, end-of-life care, organisation of oxygen services and continuation of pulmonary rehabilitation.
Key Points: positive change occurs over time and repeated audit seems to deliver some improvement in services. It is necessary to assess interventions such as the Peer Review used in the NCROP to achieve more comprehensive and rapid change.
PMCID: PMC2761897  PMID: 19778416
8.  Ergonomics in medicine and surgery 
BMJ : British Medical Journal  2004;328(7448):1115-1118.
This review outlines some of the issues surrounding ergonomics that are relevant to medical and surgical practice and to health care in general
PMCID: PMC406327  PMID: 15130981
9.  Virtual reality in surgery 
BMJ : British Medical Journal  2001;323(7318):912-915.
PMCID: PMC1121442  PMID: 11668138
12.  Survival of Microorganisms in a Rock Bed Under Conditions Simulating Solar Heat Storage 
A laboratory-scale unit containing about 360 kg of washed river gravel was designed to [ill] the use of rocks for heat storage. The unit was operated under varying conditions of temperature, relative humidity, and the addition of volatile nutrients over a 4-month period. Effluent air and rock surfaces were monitored for the presence of microorganisms. After 2 weeks, virtually no microorganisms were detected in the effluent air except when dry soil or compost was added as the inoculum. A small number of heat-resistant bacteria, but no fungi, were found to survive on the rock surfaces. Microorganisms isolated were either sporeforming bacteria or actinomycetes closely resembling Thermoactinomyces vulgaris. Microbial colonization of rock beds used for solar heat storage does not appear likely under routine operation.
PMCID: PMC243874  PMID: 16345765
13.  Inhibition of Nucleic Acid and Protein Synthesis in Mouse Spleen Cells In Vitro by Azathioprine 
Applied Microbiology  1970;20(6):910-912.
The effect of azathioprine on macromolecular biosynthesis was studied in mouse spleen cells cultured in vitro. The rate of incorporation of 3H-thymidine, 3H-uridine, and 14C-leucine into acid-insoluble material was used to measure deoxyribonucleic acid, ribonucleic acid, and protein synthesis. Results indicate that azathioprine inhibited nucleic acid and protein synthesis at levels which did not decrease cell viability.
PMCID: PMC377082  PMID: 5492440
Journal of Bacteriology  1962;84(4):724-729.
Dobrogosz, Walter J. (The Pennsylvania State University, University Park) and Robert W. Stone. Oxidative metabolism in Pediococcus pentosaceus. II. Factors controlling the formation of oxidative activities. J. Bacteriol. 84:724–729. 1962.—Studies were conducted on some factors which regulate the formation of oxidative activities in Pediococcus pentosaceus, a homofermentative lactic acid organism. Oxidative abilities were defined as the capacities to oxidize glucose and glycerol, and to exhibit catalase activity. Factors such as the type of growth substrate, the growth substrate concentration, pH, and oxygen tension were considered. The results suggested that the development of oxidative activities in this organism is under adaptive control and subject to repression by the well-known “glucose effect,” as well as by anaerobiosis. In addition to the necessity for the formation of aerobic systems for the metabolism of glycerol, which can be utilized only under aerobic conditions, data are presented which suggest that aerobic reactions may play a physiologically important role toward the induction of growth on other substrates such as d-xylose and lactose.
PMCID: PMC277949  PMID: 14028240
Journal of Bacteriology  1962;84(4):716-723.
Dobrogosz, Walter J. (Pennsylvania State University, University Park) and Robert W. Stone. Oxidative metabolism in Pediococcus pentosaceus. I. Role of oxygen and catalase. J. Bacteriol. 84:716–723. 1962.—Studies were conducted on the physiological behavior of several strains of Pediococcus pentosaceus isolated from alfalfa silages. Although these organisms are regarded as homofermentative lactic acid bacteria which metabolize carbohydrates via the classic reactions of glycolysis, this investigation showed that they were capable of developing other physiologically important reactions related to carbohydrate metabolism. Growth on glycerol, for example, was shown to depend on the development of aerobic reactions, and was directly related to the catalase content of the various strains tested. These organisms were shown to be devoid of a cytochrome system, thus implicating an active flavoprotein system in oxidative reactions. A study of the end products of aerobic glycerol metabolism suggested that glycerol was oxidized to the pyruvate level, with subsequent reactions involving pyruvate leading to the accumulation of lactate, acetate, acetoin, and CO2 in a molar ratio of approximately 1:1:1:3.
PMCID: PMC277948  PMID: 14028239
Journal of Bacteriology  1961;81(3):425-430.
PMCID: PMC279025  PMID: 13767102
Rabbit papilloma virus seems uniquely to begin its proliferation in the nucleolus of infected cells. In cells near the germinal layer of the stratum Malpighii spherical viral bodies seem to develop within a reticulum which forms out of the fine granular matrix of the nucleolus. The virus may later fill the nucleus and spread into the whole cell. The age of the cell, determined by its position in the Malpighian layer and by the extent of keratinization, can be correlated with the viral development.
PMCID: PMC2136998  PMID: 13834926
California Medicine  1955;82(3):176-178.
The results of treatment of tuberculous meningitis in Highland Alameda County Hospital, since the advent of streptomycin, in 34 cases were: dead, 21 patients, or 61 per cent; alive, 10 patients, or 29 per cent. Three cases were excluded from the ultimate report due to inadequate follow-up. The mean survival time of the ten survivors at the time of report was 35 months, the longest being 74 months.
The composite results of treatment elsewhere, as reported in the literature, have been: dead, 892, or 59 per cent; alive, 629, or 41 per cent.
The pathogenesis of the disease and the effects of chemotherapy are discussed.
A therapeutic regimen for tuberculous meningitis is presented, which has been used at Highland Hospital since INH became established as the most effective component in the combined chemotherapeutic attack on the disease.
PMCID: PMC1532755  PMID: 14351987
23.  The Tuberculin Test* 
California and Western Medicine  1932;37(2):108-111.
PMCID: PMC1658254  PMID: 18742211

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