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Low-intensity pulsed ultrasound (LIPUS) treatment of fractures has been available to the orthopaedic community for nearly three decades; however, it is still considered an experimental treatment by some clinicians, even though there is a wealth of clinical data. Based on the evaluation of clinical trial data, we have established key criteria which can lead to LIPUS success and avoid failure. These are fracture gap size and stability, accurate transducer placement and minimum treatment number. However, from a clinician’s view, the correct attitude to treatment must be observed, and this has also been discussed. It is hoped, armed with this new evaluation of the clinical data, that clinicians can treat patients with LIPUS more effectively, resulting in fewer failures of treatment.

Clozapine has proven efficacy in treatment-resistant schizophrenia, though there have been reports of untoward reactions to its use, including cases of rare side effects. The authors here describe a case of an unusual constellation of symptoms, predominantly diarrhoea, that consistently occurred over 3 attempts to treat a patient with clozapine. We conclude with a recommendation that clinicians need to be aware that new-onset diarrhoea may be an adverse reaction to clozapine.

The Tufted Titmouse Baeolophus bicolor is well known for its stereotyped “peter-peter-peter” song, but anecdotal reports of its song’s diversity also exist. We identified an atypical song in East-Central Illinois, USA, that has persisted for several years in the same vicinity. We used a spectrogram-based comparison metric to assess song similarity scores against con- and heterospecific songs from a citizen-science database. The results suggest that these novel songs may truly be outliers beyond the Tufted Titmouse’s local range of species-typical song variability. Our study also illustrates a methodological approach regarding the assessment of other, potentially atypical vocalizations recorded from birds.

The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development. CAPTURE ALS is a Canadian-based platform designed to include participants' voices in its development and through execution. Standardized methods will be used to longitudinally characterize ALS patients and healthy controls through deep clinical phenotyping, neuroimaging, neurocognitive and speech assessments, genotyping and multisource biospecimen collection. This effort plugs into complementary Canadian and international initiatives to share common resources. Here, we describe in detail the infrastructure, operating procedures, and long-term vision of CAPTURE ALS to facilitate and accelerate translational ALS research in Canada and beyond.

Ankle fractures are a common presentation to orthopaedic surgeons, with the lateral malleolus involved in 86% of cases. A soft tissue injury can be a concomitant feature of these injuries as a result of the primary injury or following secondary wound breakdown. The peroneus brevis muscle flap provides a reliable and robust option to cover the distal third of the lower limb. With an understanding of the anatomy and cautious dissection during periosteal elevation, the perforating vessels supplying the peroneus brevis can be preserved ensuring that a valuable reconstructive option is available. How to cite this article Irvine E, Cochrane E, Harwood P, et al. Surgical Exposure of the Distal Fibula to Protect the Peroneus Brevis Muscle Vascular Pedicle. Strategies Trauma Limb Reconstr 2021;16(3):176–178.

COVID-19 has changed the permeability of borders in transboundary environmental governance regimes. While borders have always been selectively permeable, the pandemic has reconfigured the nature of cross-border flows of people, natural resources, finances and technologies. This has altered the availability of spaces for enacting sustainability initiatives within and between countries. In Southeast Asia, national governments and businesses seeking to expedite economic recovery from the pandemic-induced recession have selectively re-opened borders by accelerating production and revitalizing agro-export growth. Widening regional inequities have also contributed to increased cross-border flows of illicit commodities, such as trafficked wildlife. At the same time, border restrictions under the exigencies of controlling the pandemic have led to a rolling back and scaling down of transboundary environmental agreements, regulations and programs, with important implications for environmental democracy, socio-ecological justice and sustainability. Drawing on evidence from Southeast Asia, the article assesses the policy challenges and opportunities posed by the shifting permeability of borders for organising and operationalising environmental activities at different scales of transboundary governance.

Abstract The obligate brood parasitic common cuckoo (Cuculus canorus) is best known for its two-note “cu-coo” call, which is uttered repeatedly by adult males during the breeding season. This call advertises the male’s claim for his territory. A rare, aberrant version (“cu-kee”) was discovered in a population of cuckoos in central Hungary. In a playback experiment, we simulated conspecific territorial intrusions using either aberrant call sequences or normal calls (as control). Cuckoos responded to both calls similarly by approaching the speaker, flying around it several times, and perching on nearby trees. To identify the role of each note of these cuckoo calls, we also played sequences of the first (“cu”) or second (“coo” or “kee”) notes of the calls. Territorial males responded to first notes at similarly high frequencies as to each of the full calls, whereas responses toward either second note type were nearly absent. Thus, the first notes of both typical and aberrant cuckoo calls contain sufficient information to recognize conspecific males and the novel calls did not reduce the efficiency of male-male communication in cuckoos because the aberration occurred in the less functional second note. Significance statement Birds use songs and calls to communicate with each other, including advertising their territories to keep competitors away. However, when the acoustic signal is atypical and distorted, the receiver individual may not process it correctly. Common cuckoos recognize a territorial intruder by their well-known “cu-coo” calls. We studied a rare, aberrant version of the common cuckoo call (“cu-kee”), which differed from the normal call in the second note of the two-partite call. However, cuckoos responded similarly to both of the normal and aberrant calls in a playback experiment. When the first or second parts of the different calls were played separately, only the first part of the cuckoo calls was effective in eliciting territorial defence. Consequently, the aberrant second note did not reduce cuckoos’ communication efficiency.

Hospital readmissions are an important metric of quality and safety. This study seeks to characterize the relationship between readmissions and obstructive sleep apnea (OSA). A better understanding of this relationship could be utilized to develop preventative measures and reduce readmission rates.A retrospective review of patients discharged over a 24-month period to a Department of Defense hospital was conducted. Medical records review provided demographic data, presence of OSA and comorbid diseases, and whether readmission occurred within 30 days of discharge. Statistical analysis assessed risk factors for readmission, and multivariate analysis was performed. Next, 125 readmitted patients with OSA were randomly selected for detailed chart review and compared to a matched cohort that was not readmitted.Of 22,261 unique patients discharged, 1,899 (8.5%) were readmitted. Patients with OSA had a readmission rate of 11.4% versus 7.6% for patients without OSA (This study found OSA to be an independent risk factor for readmission within 30 days of discharge. PAP therapy appears to be underutilized in patients with known OSA. Additional studies are needed to define the relationship between OSA, PAP adherence, and hospital readmission.

International audience; Recent increases in emergent infectious diseases have raised concerns about the sustainability of some marine species. The complexity and expense of studying diseases in marine systems often dictate that conservation and management decisions are made without quantitative data on population-level impacts of disease. Mark–recapture is a powerful, underutilized, tool for calculating impacts of disease on population size and structure, even in the absence of etiological information. We applied logistic regression models to mark–recapture data to obtain estimates of disease-associated mortality rates in three commercially important marine species: snow crab (Chionoecetes opilio) in Newfoundland, Canada, that experience sporadic epizootics of bitter crab disease; striped bass (Morone saxatilis) in the Chesapeake Bay, USA, that experience chronic dermal and visceral mycobacteriosis; and American lobster (Homarus americanus) in the Southern New England stock, that experience chronic epizootic shell disease. All three diseases decreased survival of diseased hosts. Survival of diseased adult male crabs was 1% (0.003–0.022, 95% CI) that of uninfected crabs indicating nearly complete mortality of infected crabs in this life stage. Survival of moderately and severely diseased striped bass (which comprised 15% and 11% of the population, respectively) was 84% (70–100%, 95% CI), and 54% (42–68%, 95% CI) that of healthy striped bass. The disease-adjusted yearly natural mortality rate for striped bass was 0.29, nearly double the previously accepted value, which did not include disease. Survival of moderately and severely diseased lobsters was 30% (15–60%, 95% CI) that of healthy lobsters and survival of mildly diseased lobsters was 45% (27–75%, 95% CI) that of healthy lobsters. High disease mortality in ovigerous females may explain the poor recruitment and rapid declines observed in this population. Stock assessments should account for disease-related mortality when resource management options are evaluated.

A free space quantum key distribution system has been demonstrated. Consideration has been given to factors such as field of view and spectral width, to cut down the deleterious effect from background light levels. Suitable optical sources such as lasers and RCLEDs have been investigated as well as optimal wavelength choices, always with a view to building a compact and robust system. The implementation of background reduction measures resulted in a system capable of operating in daylight conditions. An autonomous system was left running and generating shared key material continuously for over 7 days.

Gamma-secretase is an intramembrane-cleaving protease responsible for the final proteolytic event in the production of the amyloid-beta peptides (Abeta) implicated in Alzheimer's disease (AD). Inhibition of gamma-secretase activity is thus an attractive therapeutic strategy to slow down the pathogenesis of AD. Drugs often target more than one biomolecule because of conserved 3-dimensional structures in prospective protein binding sites. We have capitalized on this phenomenon of nature to identify new gamma-secretase inhibitors. Here we show that 2-hydroxy naphthyl derivatives, a previously identified subclass of NAD(+) analog inhibitors of sirtuin 2 (SIRT2), are direct gamma-secretase inhibitors. Subsequent structure-activity relationship studies further showed that 2-hydroxy-1-naphthaldehyde is the minimal pharmacophore for gamma-secretase inhibition. In evaluating target protein determinants of inhibition, we identified a common GXG signature nucleotide-binding site (NBS) shared by the gamma-secretase subunit presenilin-1 C-terminal fragment (PS1-CTF), SIRT2, and Janus kinase 3 (JAK3). Because a detailed 3-dimensional structure of gamma-secretase is beyond our knowledge, we took advantage of the known crystal structure of human JAK3 to model the NBS of the PS1-CTF, which includes the catalytic residue D385. Our results suggest that the flexible PS1-CTF (381)LGLG(384) loop comprises a substrate-docking site capable of recognizing specifically different gamma-secretase substrates.

In this paper, the authors discuss the modal and lasing properties of multicore photonic crystal fiber lasers in the context of high power/energy production from fiber cores with very large mode area. Supermode selection methods like Talbot imaging or far-field aperturing are tested using 6-, 7-, and 18-core fibers. It is shown that in-phase mode selection is achieved efficiently by using either method. The fibers have been tested in continuous-wave (CW) and Q-switched laser operation. The mode field area is as large as 4240 mum2 for one of the fibers, providing up to 2 mJ of pulse energy in Q-switched operations with 30 ns pulse duration.

Use of anticholinergic drugs in older people is associated with increased risk of cognitive decline and of dementia and death.We identified drugs widely used in older people and attempted to classify their anticholinergic effect on cognition (AEC) according to our three-point scale which scored AEC according to in vitro anticholinergic potency, capacity to cross the blood-brain barrier and statements made in standard texts.In total, 165 drugs were examined. We identified 21 drugs with an AEC score of 3, 18 with a score of 2, 21 with a score of 1 and 62 with a score of 0. Owing to insufficient information, we were unable to classify 43 drugs.A large number of drugs commonly used in older people are likely to be associated with cognitive impairment. Copyright © 2016 John WileySons, Ltd.

Summary The issues of cross-infection and the survival of variant Creutzfeldt Jakob disease (vCJD) on surgical instruments have highlighted the importance of cleanliness of multiple-use surgical instruments. The aim of this study was to assess the levels of total protein contamination on a wide range of surgical instruments as an indication of the effectiveness of routine cleaning and disinfection in hospitals. Anonymized trays of wrapped and autoclaved instruments were supplied to two laboratories for analysis at the stage where they would normally be returned to operating theatres. Instruments were assessed for residual protein and total organic matter. Laboratory A showed that 17% (35/206) of instruments were above a threshold that equated to 200 μg. The worst examples, a McIvor gag, a Draffin rod (child) and a Yankaur sucker, had 1.028, 1.286 and 2.228 mg of extractable protein, respectively. The median (25th, 75th percentiles) amount of protein from instruments from different hospitals assessed in Laboratory B ranged from 8 (3, 30) μg (Hospital C) to 91 (35, 213) μg (Hospital D) (P = 0.044). The residual matter washed from instruments varied from 0.62 (0.32, 0.81) mg (Hospital E) to 3.5 (3.5, 4.0) mg (Hospital A) (P = 0.0001). In one case, 45 mg of residual organic matter was washed from an instrument (split stem). In conclusion, this study demonstrated that a proportion of instruments at the point of use show levels of protein that could pose a direct cross-infection risk via prion agents and other organic contamination that may reduce the effectiveness of cleaning/disinfection strategies targeted against either prions or traditional infectious agents.

In the United Kingdom there has been a marked increase in the number of human infections caused by toxigenic Corynebacterium ulcerans . During 2002 and 2003 the organism was also isolated from several domestic cats with bilateral nasal discharge. As C. ulcerans has never previously been isolated from cats, the 16S rRNA gene from three cat isolates was sequenced to confirm their species identities. Fifty clinical isolates from the United Kingdom isolated from 1986 to 2003 and seven cat isolates were characterized by ribotyping to determine whether the ribotypes of the cat isolates were genotypically related to those found for human clinical isolates. For comparison, the genotypes of 11 overseas isolates and 13 isolates from H. R. Carne's collection isolated between 1933 and 1979 were also determined. Strains isolated from domestic cats were found to exhibit the predominant ribotypes observed among human clinical isolates, suggesting that C. ulcerans isolated from cats could be a potential reservoir for human infection.

Transmissible degenerative encephalopathy agents are relatively resistant to standard decontamination procedures. Bovine spongiform encephalopathy (BSE) agent was inactivated by sodium hypochlorite but not sodium dichloroisocyanurate; 1M or 2M sodium hydroxide was unreliable for BSE and scrapie agents. BSE infectivity survived a two‐year exposure to formol saline. Porous‐load autoclaving at 134‐138°C was ineffective with BSE and scrapie agents, and resistance to porous‐load autoclaving was enhanced by prior exposure to ethanol. Gravity displacement autoclaving at 132°C was also ineffective with BSE agent. Gravity displacement autoclaving at 121°C was effective with scrapie agent if it was exposed to 2M sodium hydroxide during autoclaving. After BSE‐spiked material was processed through facsimiles of EC rendering processes, infectivity was recoverable in the meat and bonemeal produced by four of these processes. Using scrapie‐spiked material, infectivity was recoverable in all meat and bonemeal samples except those derived from processes which used steam under pressure.

Feline chronic gingivostomatitis (FCGS) is a chronic inflammatory disease of the oral cavity that causes severe pain and distress. There are currently no specific treatment methods available and little is known regarding its aetiology, although bacteria are thought to play a major role. The purpose of this study was to identify the oral bacterial flora in normal and diseased cats. Oral swabs were obtained from the palatoglossal folds of eight cats (three normal and five FCGS) and were subjected to microbiological culture. Pasteurella pneumotropica and Pasteurella multocida subsp. multocida were the most prevalent species identified by culture methods in the normal and FCGS samples, respectively. Bacteria were also identified using culture-independent methods (bacterial 16S rRNA gene sequencing). For the normal samples, 158 clones were analysed and 85 clones were sequenced. Capnocytophaga canimorsus (10.8% of clones analysed) was the predominant species. Uncultured species accounted for 8.2% of clones analysed, and 43.7% of clones analysed represented potentially novel species. For the FCGS samples, 253 clones were analysed and 91 clones were sequenced. The predominant species was P. multocida subsp. multocida (51.8% of clones analysed). Uncultured species accounted for 8.7% of clones analysed, and 4.7% of clones analysed represented potentially novel species. It is concluded that the oral flora in cats with FCGS appears to be less diverse than that found in normal cats. However, P. multocida subsp. multocida is found to be significantly more prevalent in FCGS than in normal cats and consequently may be of aetiological significance in this disease.

Multiple-core fibers offer the possibility of creating fiber lasers with enlarged effective core diameter, while simultaneously controlling mode shape and quality. A review is presented of the basic theory used for design, and examples presented of such lasers operating in Q-switched mode. Examples of active, non-interacting, and passive multiple-core fibers are also presented.

Approximately 10,000 legal-sized male snow crabs Chionoecetes opilio were tagged and released on the commercial fishing grounds of Bonavista Bay between 1979 and 1982 inclusive, The distance that the snow crabs traveled, as determined from 4,255 recaptures, ranged from 0.6 to 74.1 km (mean, 10.7 km; median, 8.5 km). Snow crabs appeared to remain within Bonavista Bay: there was no observed movement to adjacent commercial crab-fishing areas over periods of up to 5 years. The practice of managing the fishery as a discrete unit appears to be warranted.

In amyotrophic lateral sclerosis caused by mutations in Cu/Zn-superoxide dismutase (SOD1), altered solubility and aggregation of the mutant protein implicates failure of pathways for detecting and catabolizing misfolded proteins. Our previous studies demonstrated early reduction of proteasome-mediated proteolytic activity in lumbar spinal cord of SOD1(G93A) transgenic mice, tissue particularly vulnerable to disease. The purpose of this study was to identify any underlying abnormalities in proteasomal structure. In lumbar spinal cord of pre-symptomatic mice [postnatal day 45 (P45) and P75], normal levels of structural 20S alpha subunits were incorporated into 20S/26S proteasomes; however, proteasomal complexes separated by native gel electrophoresis showed decreased immunoreactivity with antibodies to beta3, a structural subunit of the 20S proteasome core, and beta5, the subunit with chymotrypsin-like activity. This occurred prior to increase in beta5i immunoproteasomal subunit. mRNA levels were maintained and no association of mutant SOD1 with proteasomes was identified, implicating post-transcriptional mechanisms. mRNAs also were maintained in laser captured motor neurons at a later stage of disease (P100) in which multiple 20S proteins are reduced relative to the surrounding neuropil. Increase in detergent-insoluble, ubiquitinated proteins at P75 provided further evidence of stress on mechanisms of protein quality control in multiple cell types prior to significant motor neuron death.

Bitter crab disease (BCD) of snow crabs, Chionoecetes opilio, is caused by a parasitic dinoflagellate, Hematodinium sp. The disease has shown an alarming increase in prevalence in the commercial fishery in eastern and northeastern areas of Newfoundland and Labrador since it was first recorded there in the early 1990s. We documented histopathological alterations to the tissues in snow crabs with heavy infections of Hematodinium sp. and during sporulation of the parasite. Pressure necrosis was evident in the spongy connective tissues of the hepatopancreas and the blood vessels in most organs. In heavy infections, little remained of the spongy connective tissues around the hepatopancreas. Damage to the gills varied; in some cases it was severe, particularly during sporulation, involving apparent thinning of the cuticle, loss of epithelial cells, and fusion of the membranous layers of adjacent gill lamellae. Affected lamellae exhibited varying degrees of distention with a loss of trabecular cells, hemocyte infiltrations, and swelling or "clubbing" along the distal margins. Large numbers of zoospores were located along the distal margins of affected lamellae suggesting that sporulation may cause a lysis or bursting of the thin lamellar cuticle, releasing spores. Pressure necrosis, due to the build up of high densities of parasites, was the primary histopathological alteration in most tissues. Hematodinium infections in the snow crab are chronic, long-term infections that end in host death, during sporulation of the parasite.

Demanding real-time data processing applications are driving the need for high-throughput programmable logic. Improvements to computing speed from reduction of processor feature sizes are predicted, but these are expected to be hampered within the next 2-5 years by the limitations of metallic interconnects between processors. Optical interconnect alternatives have been attempted, but independent optical channel densities are, at present, restricted by conventional fiber dimensions. In this paper a novel solution to this problem is presented employing a multi-core microstructured fiber. In this type of fiber, a photonic crystal fiber (PCF), the core is a solid silica region surrounded by air holes shot through the length of the fiber. This is created by stacking capillaries and solid canes of silica to create a preform, with the structure preserved after drawing down; a core may be created by replacing an air hole by a solid cane. The criteria for the fiber design are discussed: a bit error rate restriction leads to an upper limit for cross-coupling between cores and hence the distance (or number of air holes) between each channel. Modeling indicates a final fiber design containing 37 cores 31.25 microns apart, equivalent to a density of 1150 independent channels per millimeter squared. Details of an optical transmitting/receiving system utilizing four of the channels and arrays of VCSELs as transmitters and receivers are described. Future improvements to the system are discussed.

In this paper, we show that it is possible to arrange for an 18-core photonic crystal fibre (PCF) laser to operate in the fundamental in-phase supermode. The mode divergence is as small as 12.5 mrad. The equivalent mode field diameter is about 52 μm. Mode filtering is provided by a pinhole in the far field. The laser is Q-switched using an Acousto-Optic Modulator (AOM). An output power up to 65 W at a repetition rate of 50 kHz (corresponding to 1.3 mJ per pulse), with 22 ns short pulses, has been obtained with a slope efficiency of 46%. Ongoing amplification experiments are briefly described. Limiting factors (end facet damage threshold and thermal dissipation) are discussed for further scaling of this laser concept.

We report on the laser properties of multicore photonic crystal fiber lasers. A stable phase locking of six- and seven-core structures through evanescent coupling is observed. Effective supermode selection is obtained by using both diffraction losses and the Talbot effect. A pure in-phase supermode is obtained (1.1 times diffraction limited). The laser operating in this mode has a slope efficiency of 70% with up to 44 W of output power. The modal area of the in-phase supermode multicore fiber is 1150 microm2, which makes it, to our knowledge, the single-mode fiber laser with the largest mode field area. In-phase laser action is stable when the fiber is bent.

The parasitic dinoflagellate Hematodinium sp. causes a condition known as bitter crab disease (BCD) in snow crabs Chionoecetes opilio and Tanner crabs C. bairdi. As the name of the condition implies, crabs infected with BCD are unmarketable due to their bitter flavor. We surveyed the distribution of BCD in 3 regions within the snow crab fishery of Newfoundland from 1997 to 2003. Over time, the disease has become firmly established in Conception and Bonavista Bays and persists at low levels on the Avalon fishing grounds. An epizootic occurred within Bonavista and Conception Bays in 1999 and persisted in Conception Bay in 2000, reaching prevalences of over 2% to 9% in trapped and trawled male crabs and from 19 to 26% in trawled and trapped female crabs, respectively. Infections were highest in females and small males, i.e. the unfished and pre-recruit portions of the fishery. In a mortality study, all of the naturally infected crabs died and 50% of the experimentally inoculated crabs died. Patterns in the molting cycle and prevalence of infection indicate that transmission occurs during the post-molt condition, and that overt infections probably develop 2 to 4 mo later with mortalities occurring at least 3 to 4 mo thereafter. The hydrography of this bay may have contributed to the epizootic as infections were centered within the deeper confines of the bay. Analysis of various abiotic factors uncovered a significant positive association between prevalence, depth and mud/sand substrates; the nature of this relationship was not apparent but may be related to diet or alternate hosts. Lastly, given the increase in BCD in snow crabs in Newfoundland, we recommend that fishery management programs for Chionoecetes fisheries employ non-selective gear to monitor for Hematodinium infections in female and juvenile crabs because these under-sampled members of the population may forewarn of impending recruitment declines that might otherwise remain unexplained.

We describe a free space quantum cryptography system which is designed to allow continuous unattended key exchanges for periods of several days, and over ranges of a few kilometres. The system uses a four-laser faint-pulse transmission system running at a pulse rate of 10MHz to generate the required four alternative polarization states. The receiver module similarly automatically selects a measurement basis and performs polarization measurements with four avalanche photodiodes. The controlling software can implement the full key exchange including sifting, error correction, and privacy amplification required to generate a secure key.

Laser damage thresholds of 10 and 20 micron-core diameter solid-core photonic crystal fibres (PCF) and hollow-core photonic band gap (PBG) fibres have been measured. The studies were carried out using a Nd:Yag laser (30nsec pulses at 10Hz), which is optimally coupled into the fibres by careful mode matching, providing a coupling efficiency greater than 90%. It has been shown that the damage threshold of the 10-micron PBG fibre occurs for pulse energies close to 1 mJ, equivalent to a fluence well in excess of 1kJ/cm 2 propagating down the fibre. This is a factor of 4 larger than the damage threshold of the 10-micron diameter solid-core PCF. However, the damage threshold of the large-core PBG is smaller than that of the PCF. Theoretical modelling based only on the optical modal properties of the single-mode PBG fibre shows that an enhancement by a factor 25 should be obtainable. Thus there are different mechanisms potentially responsible for the fragility of larger core PBG fibres. In an experimental study of bend losses it ahs been found that it is possible to bend the 10-micron PBG fibre up to the breaking point bend radius (less than 1mm). The critical bend radius for the 20-micron PCF. A summary will be presented of the results of the experimental and theoretical studies, highlighting possible reasons for the observed trends for the two different forms of fibre.

This paper presents a slide presentation on practical quantum key distribution. The transmitter, random number generator, receiver, and software are presented. (10 pages)

Laser damage thresholds of 8 μm- and 22 μm-core diameter solid-core photonic crystal fibres (PCF) and hollow-core photonic band gap (PBG) fibres have been measured. The studies were carried out using a 1.06 μm Nd:YAG laser (30 nsec pulses at 10 Hz), which is optimally coupled into these fibres by careful mode matching, providing a coupling efficiency greater than 90%. It has been shown that the damage threshold of the 8 μm core PBG fibre occurs at pulse energies close to 1 mJ, equivalent to a fluence well in excess of 1 kJ/cm 2 propagating down the fibre. This is a factor of 4 larger than the damage threshold of a solid-core PCF of similar core diameter. In comparison, the damage threshold of the large-core PBG is smaller than that of the equivalent PCF. Theoretical modelling based only on the optical modal properties of the single-mode PBG fibre shows that an enhancement by a factor of 25 should be obtainable. Thus there are different damage mechanisms potentially responsible for the fragility of larger-core PBG fibres. In an experimental study of bend losses it has been found that it is possible to bend the 8 μm PBG fibre up to the breaking point bend radius (

We have analysed different 1D and 2D arrays of evanescently coupled cores within a fibre laser structure. The supermodes (phase-locked modes) have been calculated using coupled mode theory. We show that without a Talbot mirror, the out-of-phase supermode has the lowest threshold. Supermode selection is obtained using a Talbot cavity. A threshold analysis is carried out and it is shown than the in-phase supermode can be selected for a densely packed array of cores. 2D core structures are much more effective than 1D core structures for in-phase supermode selection. The influence of parameters like the strength of the evanescent coupling constant or the core-to-core detunings of propagation constant on the dynamical stability of the supermodes is investigated. We give figures of the minimum bend radius for phase locking. We show that large multicore structures can potentially be bent tighter than the equivalent single large core fibre laser.

St. John's wort (Hypericum perforatum) has been identified as an effective treatment for depression in controlled studies and subsequent meta-analyses. However, 3 recently published large studies failed to demonstrate robust efficacy. Updated meta-analysis and assessment of publication bias may help determine the true effect of St. John's wort.Meta-analysis to reevaluate the effectiveness of St. John's wort as an antidepressant, funnel plot analysis, and meta-regression to assess the impact of publication bias, small-study effects, and variation in trial characteristics were performed. We conducted 2 analyses: a reproduction of a recent meta-analysis including 15 studies (Meta-15) and a meta-analysis extended by the 3 studies published since then (Meta-18). The studies in Meta-15 were identified through MEDLINE and EMBASE searches conducted in June 2000. The search terms used were St. John's wort, hypericum, hypericin, depression, and antidepressant, and no language restrictions were applied. For both meta-analyses, we compared funnel plots, Begg's rank correlation, Egger's regression, trim and fill method, and meta-regression.In both analyses, effect sizes in recent studies were smaller than those reported in earlier studies; the addition of more recent studies into the analyses resulted in reduced effect size. In Meta-15, St. John's wort was significantly more effective than placebo with a risk ratio (RR) of 1.97 (CI = 1.54 to 2.53). In Meta-18, the RR was reduced to 1.73 (CI = 1.40 to 2.14). On funnel plot analysis, the Meta-18 plot proved to be much more skewed than the Meta-15 plot. Meta-regression showed that increase in effect size was associated with smaller sample size only. The impact of baseline severity of depression could not be evaluated as the studies used different versions of the Hamilton Rating Scale for Depression.St. John's wort may be less effective in the treatment of depression than previously assumed and may finally be shown to be ineffective if future trials confirm this trend.

A validation study was carried out to determine the capacity of the traditional acid and alkaline processes used in the manufacture of bovine bone gelatine to remove and/or inactivate the transmissible agent that causes BSE (bovine spongiform encephalopathy). Using an accurately scaled down laboratory process that precisely mimicked the minimum conditions of the industrial processes, gelatine (gelatin) was manufactured from industrial starting material that had been spiked with mouse brain infected with the 301V strain of mouse-passaged BSE agent. Clearance factors were determined by titrating the infectivity levels of the infected mouse brain tissue, the gelatine extracts, and the final sterilized gelatine solution. The infectivity level of the spiked starting material was 10(8.4) mouse intracerebral ID(50)/kg (ID(50) is the dose at which half of the challenged animals were infected). Clearance factors of 10(2.6) and 10(3.7) ID(50) were demonstrated for the first stages of the acid and alkaline processes respectively during which the bones are converted to crude gelatine. It was further demonstrated that the complete acid and alkaline processes both reduced infectivity to undetectable levels, giving clearance factors of/=10(4.8) ID(50) for the acid process, and/=10(4.9) ID(50) for the alkaline process.

Variable success rates of the Valsalva maneuver in treatment of paroxysmal supraventricular tachycardia may be due to variations in performance technique. This study aimed to compare the magnitude of the vagal reflexes initiated by 5 variations of the Valsalva maneuver technique (supine, supine with epigastric pressure, supine with leg raise, semirecumbent position, and sitting position).This was a single-blinded, repeated-measures, clinical trial of 65 subjects in sinus rhythm. Subjects performed each Valsalva maneuver technique 5 times in random order. The means of the longest ECG R-R intervals during the relaxation phase (postmaneuver R-R interval) and the postmaneuver pulse rates for each technique were compared. The mean differences between the pre- and postmaneuver R-R intervals for each technique were also compared.The supine with epigastric pressure and supine techniques resulted in longer mean postmaneuver R-R intervals (1.082 seconds [95% confidence interval (CI) 1.045 to 1.119 seconds] and 1.075 seconds [95% CI 1.035 to 1.114 seconds], respectively) than the leg raise, semirecumbent, and sitting position techniques (1.053 seconds [95% CI 1.019 to 1.086 seconds], 1.044 seconds [95% CI 1.006 to 1.081 seconds], and 1.024 seconds [95% CI 0.990 to 1.059 seconds], respectively), which equates to slower mean postmaneuver pulse rates for the supine with epigastric pressure and supine techniques (55.5 and 55.8 beats/min, respectively) than the leg raise, semirecumbent, and sitting position techniques (57.0, 57.5, and 58.6 beats/min, respectively). The supine with epigastric pressure and supine techniques also resulted in the largest premaneuver versus postmaneuver differences.For healthy subjects in sinus rhythm, the supine with epigastric pressure and supine techniques generated stronger vagal responses, as measured by R-R intervals and pulse rates, than the other techniques examined. However, the vagal responses of these 2 techniques were similar, and the addition of epigastric pressure may confer little advantage.

Thermostable proteases have been investigated for their ability to provide a novel biological solution to decontamination of prion agents responsible for transmissible spongiform encephalopathies (TSEs). Proteases were identified that digested total mouse brain homogenate (MBH) protein from uninfected mice. These proteases were then evaluated for digestion of BSE (301V) infectious MBH over a range of pH and temperatures, screened for loss of anti-prion antibody 6H4 immunoreactivity and protease-treated infectious MBH assessed in mouse bioassay using VM mice. Despite a number of proteases eliminating all 6H4-immunoreactive material, only the subtilisin-enzyme Properase showed a significant extension in incubation period in mouse bioassays following a 30-min incubation at 60 degrees C and pH 12. These results demonstrate the potential of the method to provide a practical solution to the problems of TSE contamination of surgical instruments and highlight the inadequacy of using Western blot for assessment of decontamination/inactivation of TSE agents.

From the preceding Chapters the reader will already have become aware of the unusual characteristics of the transmissible spongiform encephalopathies (TSEs) and the unconventional nature of their incompletely-characterised causal agents. A notable property of these agents, which will be addressed in this Chapter, is their remarkable degree of resistance to a wide range of chemical and physical inactivation procedures that are effective with conventional microorganisms [1]. As will be discussed, this has a number of implications for the safe handling of TSE-infected materials in the laboratory.

Treatment of alcohol dependence generally requires more intensive treatment than brief interventions. This may include a withdrawal programme (detoxification) to enable the dependent subject to stop drinking, and ongoing interventions to remain abstinent such as counselling, pharmacotherapy and self-help programmes. Treatment and maintenance of abstinence from alcohol involves the use of pharmacotherapy in combination with psychosocial interventions such as cognitive behaviour therapy.

The mechanism by which humans became infected with the BSE agent is discussed, and the matter of potential person-to person transmission of TSEs through contagion or medical procedures is considered. There is some discussion regarding the current evidence relating to whether or not the blood of humans infected with TSEs is infectious. Considerable emphasis is placed on the fact that TSE agents are known to be relatively resistant to decontamination by procedures that are effective with conventional micro-organisms, including (under worst-case conditions) the autoclaving procedures used to sterilise surgical instruments. Methods for providing additional re-assurance with regard to the safety of instruments are described. Safety in the pathology laboratory is discussed extensively because TSE agents are not inactivated by the usual processes used to fix tissues, and such laboratories will receive fixed tissues that are still highly infectious as far as TSE agents are concerned.

Risperidone and olanzapine are thought to have broadly similar clinical effects. This study was designed as a cost analysis study comparing costs and basic clinical outcomes of treatment with risperidone or olanzapine in a naturalistic setting.The U.K. Risperidone Olanzapine Drug Outcomes Studies in Schizophrenia (RODOS-UK) program consisted of a retrospective review of medical notes and prescription charts for 501 patients with schizophrenia or schizoaffective disorder who had been admitted to the hospital for the treatment of psychosis. The main outcome measure was cost of inpatient drug treatment. Clinical outcomes (clinician-assessed and -documented effectiveness, time to discharge) were also evaluated. Data were collected and verified between June and September 2000.Clinical outcomes were similar for risperidone and olanzapine. Clinician-assessed effectiveness was similar for both treatments (78% risperidone, 74% olanzapine; p =.39), but mean time to documented onset of effectiveness was significantly shorter for those treated with risperidone versus olanzapine (17.6 vs. 22.4 days; p =.01). Risperidone-treated patients stayed a mean of 9 fewer days in the hospital compared with olanzapine-treated patients (49 vs. 58 days; p =.007). The possibility that these observed differences were a result of different baseline characteristics could not be entirely discounted. Mean +/- SD doses of risperidone and olanzapine were 5.5 +/- 2.4 mg/day and 14.1 +/- 4.7 mg/day, respectively. The mean daily cost of all inpatient drugs was significantly higher for olanzapine than for risperidone (pound 5.63 vs. pound 3.92; p.0001). Mean total costs of all inpatient drugs were significantly higher for olanzapine than for risperidone (pound 164 vs. pound 96; p.0001), which partly reflected the longer mean treatment duration for olanzapine compared with risperidone (44 vs. 37 days). Concomitant antipsychotic use was similar for both groups (66% risperidone, 67% olanzapine). The number of patients documented as experiencing adverse events was not different between groups (22% risperidone, 19% olanzapine; p =.32).Risperidone and olanzapine produced broadly comparable clinical outcome in this cohort of hospitalized patients, but the use of risperidone was associated with significantly lower drug treatment costs.

Treatment resistant or refractory schizophrenia is a difficult to define condition of largely unknown prevalence. For 10 years, clozapine has been the standard treatment in this condition and is recognized unequivocally as being effective. However, clozapine is sometimes poorly tolerated and has the potential for severe toxicity. Partly as a result of this, other atypicals have recently been evaluated as treatments for refractory schizophrenia. In order to evaluate the evidence base relating to the drug treatment of refractory schizophrenia, we developed a refractoriness rating based on previous work. Using this rating, we assessed all trials of atypicals in schizophrenia unresponsive to at least one drug. Overall, clozapine was consistently shown to be effective in refractory schizophrenia, even when stringently defined. Data relating to olanzapine and risperidone are equivocal at best, and there is some evidence to suggest that they are less effective than clozapine. There is essentially no cogent evidence to support the use of any other atypical in refractory schizophrenia. Clozapine remains the drug of choice in this condition.

Prions are very resistant to inactivation, and accidental transmission has occurred through the use of inadequate decontamination procedures. Strong sodium hypochiorite solutions achieve inactivation but other chlorine-releasing compounds are less effective. 2M sodium hydroxide leads to substantial but incomplete inactivation; other chemical procedures such as the use of proprietary phenolic disinfectants are much less less effective. Infectivity can survive autoclaving at 132-138 degrees C, and under certain conditions the effectiveness of autoclaving actually declines as the temperature is increased. The small resistant subpopulations that survive autoclaving are not inactivated by simply re-autoclaving, and they acquire biological characteristics that differentiate them from the main population. Despite the limitations of autoclaving, combining autoclaving (even at 121 degrees C) with a sodium hydroxide treatment is extremely effective. Protein-fixation (e.g., by ethanol or formalin) substantially enhances the thermostability of these agents. This suggests that future successful inactivation strategies might best be developed by studying procedures that avoid protein-fixation.

The unconventional agents that cause transmissible degenerative encephalopathies, such as bovine spongiform encephalopathy, scrapie, and Creutzfeldt-Jakob disease (CJD), are relatively resistant to inactivation by standard decontamination procedures. The only methods that appear to be completely effective under worst-case conditions are strong sodium hypochlorite solutions or hot solutions of sodium hydroxide. Other procedures that result in significant degrees of inactivation are described. The infectivity levels in histologically-fixed tissue can be reduced substantially by treatment with concentrated formic acid without adversely affecting the microscopic quality of the tissue. Copyright 2000 Harcourt Publishers Ltd