GRD-1/PTR-11, the C. elegans hedgehog/patched-like morphogen-receptor pair, modulates developmental rate.

Both hedgehog (Hh) and target of rapamycin complex 2 (TORC2) are central, evolutionarily conserved signaling pathways that regulate development and metabolism. In C. elegans, loss of the essential TORC2 component RICTOR (rict-1) causes delayed development, shortened lifespan, reduced brood, small size and increased fat. Here, we report that knockdown of both the hedgehog-related morphogen grd-1 and its patched-related receptor ptr-11 rescues delayed development in TORC2 loss-of-function mutants, and grd-1 and ptr-11 overexpression delays wild-type development to a similar level to that in TORC2 loss-of-function animals. These findings potentially indicate an unexpected role for grd-1 and ptr-11 in slowing developmental rate downstream of a nutrient-sensing pathway. Furthermore, we implicate the chronic stress transcription factor pqm-1 as a key transcriptional effector in this slowing of whole-organism growth by grd-1 and ptr-11. We propose that TORC2, grd-1 and ptr-11 may act linearly or converge on pqm-1 to delay organismal development.

A consensus-based practical and daily guide for the treatment of acne patients.

BACKGROUND: Many current guidelines provide detailed evidence-based recommendations for acne treatment. OBJECTIVE: To create consensus-based, simple, easy-to-use algorithms for clinical acne treatment in daily office-based practice and to provide checklists to assist in determining why a patient may not have responded to treatment and what action to take. METHODS: Existing treatment guidelines and consensus papers were reviewed. The information in them was extracted and simplified according to daily clinical practice needs using a consensus-based approach and based on the authors' clinical expertise. RESULTS: As outcomes, separate simple algorithms are presented for the treatment of predominant comedonal, predominant papulopustular and nodular/conglobate acne. Patients with predominant comedonal acne should initially be treated with a topical retinoid, azelaic acid or salicylic acid. Fixed combination topicals are recommended for patients with predominant papulopustular acne with treatment tailored according to the severity of disease. Treatment recommendations for nodular/conglobate acne include oral isotretinoin or fixed combinations plus oral antibiotics in men, and these options may be supplemented with oral anti-androgenic hormonal therapy in women. Further decisions regarding treatment responses should be evaluated 8 weeks after treatment initiation in patients with predominant comedonal or papulopustular acne and 12 weeks after in those with nodular/conglobate acne. Maintenance therapy with a topical retinoid or azelaic acid should be commenced once a patient is clear or almost clear of their acne to prevent the disease from recurring. The principal explanations for lack of treatment response fall into 5 main categories: disease progression, non-drug-related reasons, drug-related reasons, poor adherence, and adverse events. CONCLUSION: This practical guide provides dermatologists with treatment algorithms adapted to different clinical features of acne which are simple and easy to use in daily clinical practice. The checklists to establish the causes for a lack of treatment response and subsequent action to take will facilitate successful acne management.

Photonic wire biosensor microarray chip and instrumentation with application to serotyping of Escherichia coli isolates.

A complete photonic wire molecular biosensor microarray chip architecture and supporting instrumentation is described. Chip layouts with 16 and 128 independent sensors have been fabricated and tested, where each sensor can provide an independent molecular binding curve. Each sensor is 50 µm in diameter, and consists of a millimeter long silicon photonic wire waveguide folded into a spiral ring resonator. An array of 128 sensors occupies a 2 × 2 mm2 area on a 6 × 9 mm2 chip. Microfluidic sample delivery channels are fabricated monolithically on the chip. The size and layout of the sensor array is fully compatible with commercial spotting tools designed to independently functionalize fluorescence based biochips. The sensor chips are interrogated using an instrument that delivers sample fluid to the chip and is capable of acquiring up to 128 optical sensor outputs simultaneously and in real time. Coupling light from the sensor chip is accomplished through arrays of sub-wavelength surface grating couplers, and the signals are collected by a fixed two-dimensional detector array. The chip and instrument are designed so that connection of the fluid delivery system and optical alignment are automated, and can be completed in a few seconds with no active user input. This microarray system is used to demonstrate a multiplexed assay for serotyping E. coli bacteria using serospecific polyclonal antibody probe molecules.

Effect of a training week on heart rate variability in elite youth rugby league players.

The aim of this study was to examine the influence of weekly training including a competitive game on heart rate (HR) variability (HRV). Youth players (n=9, age 17-20 years) were monitored during daily supine rest (10 min) and standing (8 min), 5 times over 8 days. Heart rate recordings were analysed for time domain, frequency (e. g. low frequency [LF], high frequency [HF]) domain and non-linear measures of HRV and compared using ANOVA or Friedman's tests. Relationships between HRV and training workloads were examined via Spearman rank rho (ρ) correlation coefficients. Prior to a game, mean HR was significantly increased and remained elevated until 2 days post-game while parasympathetic modulations (HF) were significantly reduced (p<0.05). The supine to standing change in HRV was significantly reduced for up to 4 days post-game (LF/HF ratio, - 1.0±2.9 vs. - 3.0±1.9, p<0.05). These results confirm that prior to a game, players exhibited reduced parasympathetic and/or predominant sympathetic modulation with the game significantly reducing autonomic responses to standing for up to the following 4 days. Identification of day to day fluctuations in HRV may provide a helpful tool for monitoring player workload to maximise training and game performance.

Influence of cycle ergometer type and sex on assessment of 30-second anaerobic capacity and power.

This study examined the influence of cycle ergometer type and sex on assessment of 30-s anaerobic capacity and power. 41 healthy adults performed a 30-s anaerobic cycle test using a mechanically- (ME) and air-braked (AE) ergometer in a randomised order, approximately 7 days apart. Peak heart rate (HR) and rating of perceived exertion were similar between tests with peak HR greater for females compared to males (187.0 ± 9.1 vs. 180.8 ± 9.9 bpm, p<0.05). Peak power (1 100 ± 330 vs. 802 ± 225 W), mean power (793 ± 223 vs. 587 ± 156 W) and total work (23.8 ± 6.7 vs. 17.6 ± 4.7 kJ) were greater for AE compared to ME (p<0.001) and greater for males compared to females (p<0.001). The mean difference for anaerobic capacity and power between AE and ME were similar for males and females (37-41% vs. 33-35%, p>0.05). Peak lactate was greater for AE compared to ME (16.1 ± 3.4 vs. 14.8 ± 2.9 mmol·L (-1); p<0.05) and greater for males compared to females (16.2 ± 3.5 vs. 14.6 ± 2.7 mmol·L (-1); p<0.05). The current study demonstrated that anaerobic power and capacity were substantially greater when assessed using AE compared to the traditional ME with the difference between ergometer types unaffected by sex. Ergometer type should be considered when comparing anaerobic results across populations and/or studies.

Analysis of styles of play according to season and end of season rank in the National Rugby League.

OBJECTIVES: This study aimed to identify styles of play in the National Rugby League (NRL) relative to season and end of season rank (position on the NRL ladder) across the 2015-2019 seasons. DESIGN: Retrospective, longitudinal analysis of performance indicators. METHODS: Forty-eight performance indicators (e.g. runs, tackles) from all NRL teams and matches during the 2015-2019 seasons (n=2010) were quantified. Principal component analysis (PCA) was then used to identify styles of play based on dimensions (Factors) of performance indicators. Multivariate analysis of covariance (MANCOVA) was then used to explain these emergent styles of play relative to 'season' and 'end of season rank'. RESULTS: The PCA revealed nine Factors (six attacking, two defensive and one contested style) accounting for ∼51% of seasonal team performance variance. These nine Factors differed across 'seasons', with four showing an effect against 'end of season rank'. From these four, two Factors (ball possession and player efforts) impacted upon the combined effects of 'season' and 'end of season rank'. CONCLUSIONS: The PCA identified nine Factors reflecting a spread of attacking, defensive and contested styles of play within the NRL. These styles differed relative to season and a team's end of season ranking. These results may assist practitioners with the recognition of more contemporary styles of play in the NRL, enabling the development of strategies to exploit competition trends.

Examining the evolution and classification of player position using performance indicators in the National Rugby League during the 2015-2019 seasons.

OBJECTIVES: This study aimed to: 1) examine recent seasonal changes in performance indicators for different National Rugby League (NRL) playing positions; and 2) determine the accuracy of performance indicators to classify and discriminate positional groups in the NRL. DESIGN: Retrospective, longitudinal analysis of individual performance metrics. METHODS: 48 performance indicators (e.g. passes, tackles) from all NRL games during the 2015-2019 seasons were collated for each player´s match-related performance. The following analyses were conducted with all data: (i) one-way ANOVA to identify seasonal changes in performance indicators; (ii) principal component analysis (PCA) to group performance indicators into factors; (iii) two-step cluster analysis to classify playing positions using the identified factors; and (iv) discriminant analysis to discriminate the identified playing positions. RESULTS: ANOVA showed significant differences in performance indicators across seasons (F=2.3-687.7; p=0-0.05; partial η2=0.00-0.075). PCA pooled all performance indicators and identified 14 factors that were included in the two-step cluster analysis (average silhouette=0.5) that identified six positional groups: forwards, 26.7%, adjustables, 17.2%, interchange, 23.2%, backs, 20.9%, interchange forwards, 5.5% and utility backs, 6.5%. Lastly, discriminant analysis revealed five discriminant functions that differentiated playing positions. CONCLUSIONS: Results indicated that player's performance demands across different playing positions did significantly change over recent seasons (2015-2019). Cluster analysis yielded a high-level of accuracy relative to playing position, identifying six clusters that best discriminated positional groups. Unsupervised analytical approaches may provide sports scientists and coaches with meaningful tools to evaluate player performance and future positional suitability in RL.

Silicon-on-insulator guided mode resonant grating for evanescent field molecular sensing.

We present experimental and theoretical results of label-free molecular sensing using the transverse magnetic mode of a 0.22 mum thick silicon slab waveguide with a surface grating implemented in a guided mode resonance configuration. Due to the strong overlap of the evanescent field of the waveguide mode with a molecular layer attached to the surface, these sensors exhibit high sensitivity, while their fabrication and packaging requirements are modest. Experimentally, we demonstrate a resonance wavelength shift of approximately 1 nm when a monolayer of the protein streptavidin is attached to the surface, in good agreement with calculations based on rigorous coupled wave analysis. In our current optical setup this shift corresponds to an estimated limit of detection of 0.2% of a monolayer of streptavidin.

Cysteamine: differential x-ray protective effect on Chinese hamster cells during the cell cycle.

Cysteamine present during x-irradiation protects synchronized Chinese hamster cells in culture against lethal damage at all stages of the cell cycle. The effect is greatest for cells irradiated at sensitive stages such as G(1) and least for resistant cells; for example, late S (dose-modifying factors 4.2 and 2.7, respectively). The effect of 50 millimolar cysteamine is to render almost invariant the normally variant x-ray age response for lethality. This suggests that there are two components of x-ray damage, only one of which is age dependent, and it is against this component that cysteamine protects the cell. Cystamine, however, has no protective effect upon these cells at any stage of the cell cycle.

The reliability of VO2(peak) determination in healthy females during an incremental arm ergometry test.

This study examined the reliability of an incremental arm ergometry (AE) protocol during peak aerobic power (VO2(peak)) determination in healthy females. Fifteen females completed two incremental AE tests to exhaustion, seven to eleven days apart, using a mechanically braked arm ergometer. The initial work rate was 16W and increased by 16W every two minutes until exhaustion. Significant differences between tests were determined by repeated measures ANOVA, and paired t-tests or Wilcoxon signed-rank tests, where appropriate. Reliability was determined by intraclass correlation coefficients (ICC), typical error, coefficient of variation (CV) and measurement bias/ratio and 95% limits of agreement (LOA). Peak cardio-respiratory responses were similar between tests, except for tidal volume (1.95 +/-0.47 vs. 1.81 +/- 0.41 L, P<0.05). Reliability for peak variables was moderate to high (ICC=0.659-0.941; CV< or =10%) while LOA were considerable for most variables including VO2(peak) (LOA=0.57 L.min(-1)). Similar peak cardio-respiratory responses, low CV and moderate-high ICC confirmed the reliability of the current incremental AE protocol to be similar to that of prior reported protocols for VO2(peak) determination. Substantial within-participant variability (LOA) for respiratory rate and tidal volume was common during the AE protocol and possibly reflects the influence of respiratory entrainment on reliability that requires further investigation.

A community change in the algal endosymbionts of a scleractinian coral following a natural bleaching event: field evidence of acclimatization.

The symbiosis between reef-building corals and their algal endosymbionts (zooxanthellae of the genus Symbiodinium) is highly sensitive to temperature stress, which makes coral reefs vulnerable to climate change. Thermal tolerance in corals is known to be substantially linked to the type of zooxanthellae they harbour and, when multiple types are present, the relative abundance of types can be experimentally manipulated to increase the thermal limits of individual corals. Although the potential exists for this to translate into substantial thermal acclimatization of coral communities, to date there is no evidence to show that this takes place under natural conditions. In this study, we show field evidence of a dramatic change in the symbiont community of Acropora millepora, a common and widespread Indo-Pacific hard coral species, after a natural bleaching event in early 2006 in the Keppel Islands (Great Barrier Reef). Before bleaching, 93.5% (n=460) of the randomly sampled and tagged colonies predominantly harboured the thermally sensitive Symbiodinium type C2, while the remainder harboured a tolerant Symbiodinium type belonging to clade D or mixtures of C2 and D. After bleaching, 71% of the surviving tagged colonies that were initially C2 predominant changed to D or C1 predominance. Colonies that were originally C2 predominant suffered high mortality (37%) compared with D-predominant colonies (8%). We estimate that just over 18% of the original A. millepora population survived unchanged leaving 29% of the population C2 and 71% D or C1 predominant six months after the bleaching event. This change in the symbiont community structure, while it persists, is likely to have substantially increased the thermal tolerance of this coral population. Understanding the processes that underpin the temporal changes in symbiont communities is key to assessing the acclimatization potential of reef corals.

Mitotic delay and chromosomal aberrations induced by X rays in synchronized Chinese hamster cells in vitro.

Synchronized Chinese hamster cell populations in vitro were X-irradiated at different stages of the cell cycle and examined at the next metaphase. Mitotic delay varied according to the stage of the cell cycle at the time of irradiation. It was greatest for cells irradiated in middle to late S, moderate for cells irradiated in G2, and least for cells irradiated in G1. It increased approximately linearly with dose (0.7 hr./100 rad for S cells and 0.3 hr./100 rad for G1 cells). Chromosomal aberration rates also depended on the stage of the cell cycle at which the cells were irradiated. Chromatid aberrations were induced mostly during G2 and S (more in early S than late S), while chromosome aberrations were induced mainly in G1. Total breaks after 500 or 750 R showed a minimum frequency in late S and a maximum frequency in G2. This form of response correlates, but only in a general qualitative way, with the dependence of survival on cell cycle stage previously reported. Mitotic delay has a dependence on cell cycle stage quite different from either chromosomal aberrations or survival.

Radiation protection recommendations on dose limits: the role of the NCRP and the ICRP and future developments.

The purpose of this paper is to review the role of the National Council on Radiation Protection and Measurements (NCRP) and the International Commission on Radiological Protection (ICRP) in making recommendations on dose limits for ionizing radiation exposure for workers and for the public. The text describes the new limits for workers and public recommended by ICRP in 1991 and NCRP in 1993 and the composition of the radiation health detriment on which they are based. The main component of this detriment is the risk of radiation induced cancer which is now estimated to be about three times greater than a decade or so earlier. Uncertainties in these risk estimates are discussed. Some special radiation protection problems, such as those for the embryo or fetus are described. The article also addresses future progress in radiation protection particularly with regard to future improvements in the scientific basis for radiation protection recommendations.

Idiopathic hemochromatosis: case report of a patient presenting with neurologic symptoms.

Idiopathic hemochromatosis is an iron-storage disease more common in men than in women. It is characterized clinically by diabetes mellitus, cirrhosis of the liver, pigmentation of the skin and cardiac failure. The diagnosis may be overlooked when the presenting symptoms do not follow the pattern. A case is reported which was diagnosed after an onset that featured neurologic symptoms.

Effects of nitrous oxide on psychological performance. A dose-response study using inhalation of concentrations up to 15%.

In this six-period randomised double-blind study, 12 healthy volunteers inhaled mixtures of nitrous oxide at concentrations of 0% (placebo); 3%, 5%, 7%, 10%, and 15% in oxygen. Each concentration was inhaled for 55 min, each period being on a separate day. The order of treatments was randomised using a Latin-Square design. The effects of nitrous oxide were assessed using a battery of performance tests which included measures of attention, psychomotor function, memory and cognition. Mood was assessed using visual analogue scales. Measures of attention and psychomotor performance showed impairment at 15% nitrous oxide, and subjective measures showed sedation at this dose. The Buschke Selective Reminding Task showed impairment to long-term recall at all doses of nitrous oxide compared to placebo, while short-term recall was impaired only at 15%. These results suggest that consolidation of memory may be particularly sensitive to disruption as a result of CNS depression.

Failla memorial lecture. Risk, research, and radiation protection.

Radiation protection concerns the risk of stochastic late effects, especially cancer, and limits on radiation exposure both occupationally and for the public tend to be based on these risks. The risks are determined, mainly by expert committees, from the steadily growing information on exposed human populations, especially the survivors of the atomic bombs dropped in Japan in 1945. Risks of cancer estimated up to the early 1980s were in the range 1 to 5 X 10(-2)/Sv, but recent revisions in the dosimetry of the Japanese survivors and additional cycles of epidemiological information suggest values now probably at the high end of this range. These are likely to require an increase in the values used for radiation protection. A major problem with risk estimation is that data are available only for substantial doses and must be extrapolated down to the low-dose region of interest in radiation protection. Thus the shape of the dose-response curve is important, and here we must turn to laboratory research. Of importance are studies involving (1) dose rate, which affects the response to low-LET radiation and often to high-LET radiation as well; (2) radiation quality, since the shapes of the dose-response curves for high- and low-LET radiation differ and thus the RBE, the ratio between them, varies, reaching a maximum value RBEM at low doses; and (3) modifiers of the carcinogenic response, which either enhance or reduce the effect of a given dose. Radiation protection depends both on risk information, and especially also on comparisons with other occupational and public risks, and on research, not only for extrapolations of risk to low doses but also in areas where human information is lacking such as in the effects of radiation quality and in modifications of response.

X-ray sensitivity of synchronized Chinese hamster cells irradiated during hypoxia.

Synchronized Chinese hamster cells were irradiated in air and in nitrogen at various points in the cell cycle. The irradiations were carried out after flushing with air or nitrogen with the medium removed from the mono-layer of cells. Under these conditions the dose-modifying factor, or oxygen enhancement ratio, was between 2.0 and 2.3 for survival in asynchronous cells. The variation in x-ray sensitivity evident as the cell progresses through its cycle was not differentially affected by its state of oxygenation at the time of irradiation. The x-ray age-response curves for irradiation in air and in nitrogen were similar at each point, except for the dose-modifying factor. This was true not only for the cells of a normal short generation time (10 hours) subline of the V79 line but also for a longer generation time (with longer GC period) subline derived from a "small colony". The variation in radiosensitivity as the cell progresses through its cycle must therefore be due to factors other than change in oxygen tension within the cell. The fact that the same variation in x-ray sensitivity with age exists for hypoxic cells as for well-oxygenated cells has a bearing on the radiotherapy of tumors which contain cells at low oxygen tensions.

The linear no-threshold response: why not linearity?

ICRP and NCRP recommend risk coefficients for use in radiation protection that are based on a linear quadratic response in the low dose region. This is a derivative of the linear no threshold (LNT) hypothesis with allowance for low dose and dose rate effects. The risk coefficients are derived from the Lifespan Study of the A-bomb survivors but are supported by many other epidemiological studies some, such as occupational, at low doses. Nevertheless, the risk coefficients are uncertain and range (90% confidence intervals) over a factor of 2-3 above and below the nominal values. Various possible dose responses in the low dose region are considered including those that may result from adaptive responses. Laboratory studies show linearity in some systems to doses as low as 2.5 mGy. Epidemiological studies include several with significant excess risks at 100 mGy or less with at least one at 10 mGy. The linear quadratic response seems, therefore, the most likely response in the very low dose region. Adopting the linear quadratic response in the low dose region does not prevent common sense judgements about dismissing small radiation risks. NCRP defined first a negligible individual risk (1987) and then an individual dose (1993) to encourage common sense judgements in the low dose region. More consideration might be given to dismissing minor risks in common sense applications in radiation protection.

Validity and sensitivity of a pen computer battery of performance tests.

This study compared administration of performance tests and visual analogue scales (VAS) using a newly developed pen computer (PenC) battery with established tests using either pencil-and-paper (PP) or conventional computer. The performance of 47 subjects (23 male, age 18-45 years, weight 51-112 kg) was compared on the two systems after a dose of ethanol (0.8 g/kg up to a maximum of 60 g for males, 50 g for females) or placebo in a double-blind two-period randomized crossover study. Mean (SD) blood ethanol concentrations (breathalyser) were 94.5 mg/100 ml (21.9) at the start of the test battery (30 min post-drink) and 80.2 (13.0) at the end of the battery (75 min post-drink). Ethanol effects were found in all tests, with most outcome measures showing significant slowing or loss of accuracy. Results from the Rapid Visual Information Processing, Sentence Verification and Continuous Attention tasks show that the ethanol-placebo difference and the statistical significance of this difference are in close correspondence for the two modes of administration. The pen computer versions of these tasks may therefore be used as direct replacements for the previous versions. Digit-Symbol and maze tasks did not correspond so closely both showing differences in the speed-accuracy trade-off between the two modes. These tests, however, are sensitive to the effects of ethanol, and may be useful in their own right. Principal component analysis suggested that VAS may be grouped into two factors: (1) 'functional integrity', including measures of alertness and perceived proficiency, and (2) 'mood', including happiness and sociability. Factor 1 showed substantial effects of ethanol, while factor 2 was unchanged. There was close agreement between the results from PP and PenC for both factors as well as for the Sober-Drunk scale, which showed the expected effects of ethanol. Thus pen computer VAS perform in a similar way to the PP versions.