The Anti-G0 Manifesto: Should a problematic construct (G0) with no biological reality be removed from the cell cycle? Yes!

It is widely accepted that there exists a "resting" or "quiescent" state where a growing cell leaves the cell cycle to enter what is often called the "G0-phase." I propose that there is no biological reality to the "G0-phase." The experimental basis for proposing a G0-phase is re-examined and re-analyzed here showing that the G0-phase is an anthropomorphic construct with no biological reality.

The influence of maturation on exercise-induced cardiac remodelling and haematological adaptation.

Cardiovascular and haematological adaptations to endurance training facilitate greater maximal oxygen consumption ( V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ ), and such adaptations may be augmented following puberty. Therefore, we compared left ventricular (LV) morphology (echocardiography), blood volume, haemoglobin (Hb) mass (CO rebreathing) and V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ in endurance-trained and untrained boys (n = 42, age = 9.0-17.1 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 61.6 ± 7.2 ml/kg/min, and n = 31, age = 8.0-17.7 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 46.5 ± 6.1 ml/kg/min, respectively) and girls (n = 45, age = 8.2-17.0 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 51.4 ± 5.7 ml/kg/min, and n = 36, age = 8.0-17.6 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 39.8 ± 5.7 ml/kg/min, respectively). Pubertal stage was estimated via maturity offset, with participants classified as pre- or post-peak height velocity (PHV). Pre-PHV, only a larger LV end-diastolic volume/lean body mass (EDV/LBM) for trained boys (+0.28 ml/kg LBM, P = 0.007) and a higher Hb mass/LBM for trained girls (+1.65 g/kg LBM, P = 0.007) were evident compared to untrained controls. Post-PHV, LV mass/LBM (boys: +0.50 g/kg LBM, P = 0.0003; girls: +0.35 g/kg LBM, P = 0.003), EDV/LBM (boys: +0.35 ml/kg LBM, P < 0.0001; girls: +0.31 ml/kg LBM, P = 0.0004), blood volume/LBM (boys: +12.47 ml/kg LBM, P = 0.004; girls: +13.48 ml/kg LBM, P = 0.0002.) and Hb mass/LBM (boys: +1.29 g/kg LBM, P = 0.015; girls: +1.47 g/kg LBM, P = 0.002) were all greater in trained versus untrained groups. Pre-PHV, EDV (R2adj  = 0.224, P = 0.001) in boys, and Hb mass and interventricular septal thickness (R2adj  = 0.317, P = 0.002) in girls partially accounted for the variance in V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ . Post-PHV, stronger predictive models were evident via the inclusion of LV wall thickness and EDV in boys (R2adj  = 0.608, P < 0.0001), and posterior wall thickness and Hb mass in girls (R2adj  = 0.490, P < 0.0001). In conclusion, cardiovascular adaptation to exercise training is more pronounced post-PHV, with evidence for a greater role of central components for oxygen delivery. KEY POINTS: It has long been hypothesised that cardiovascular adaptation to endurance training is augmented following puberty. We investigated whether differences in cardiac and haematological variables exist, and to what extent, between endurance-trained versus untrained, pre- and post-peak height velocity (PHV) children, and how these central factors relate to maximal oxygen consumption. Using echocardiography to quantify left ventricular (LV) morphology and carbon monoxide rebreathing to determine blood volume and haemoglobin mass, we identified that training-related differences in LV morphology are evident in pre-PHV children, with haematological differences also observed between pre-PHV girls. However, the breadth and magnitude of cardiovascular remodelling was more pronounced post-PHV. Cardiac and haematological measures provide significant predictive models for maximal oxygen consumption ( V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ ) in children that are much stronger post-PHV, suggesting that other important determinants within the oxygen transport chain could account for the majority of variance in V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ before puberty.

Short-Term Effects of "Composite" Training on Strength, Jump, and Sprint Performance in Hurling Players.

ABSTRACT: Byrne, PJ, Moody, JA, Cooper, S-M, Farrell, E, and Kinsella, S. Short-term effects of "composite training" on strength, jump, and sprint performance in hurling players. J Strength Cond Res 36(8): 2253-2261, 2022-The purpose of this study was to compare the short-term effects of "composite" training to sprint training on strength, jump, and sprint acceleration performance in hurling players. A randomized counterbalanced group design with baseline test, pretest and post-test measures was used. Twenty-five hurling players volunteered to participate and 21 completed the study. Subjects were divided into a "composite" (COMP group, n = 10) or a sprint training (SPRINT group, n = 11) group. Both groups trained twice per week for 7 weeks with the SPRINT group performing 6 repetitions of 20 m sprints and the COMP group completing 6 repetitions (1 repetition = 3 bounce drop jumps [BDJs] with a 20 m sprint after 15 seconds recovery). Significant differences existed pretraining to post-training for the COMP group for BDJ contact time (-7.25%; p = 0.05) and countermovement jump (CMJ) variables (height: 7.43%, p = 0.006; force: 5.24%, p = 0.05; power: 15.11%, p = 0.001). No significant differences were found between groups at baseline and for group by time interactions. Significant improvements were observed pretraining to post-training in both groups for the following: absolute 3 repetition maximum (3RM) back squat strength (12.73-17.62%, p = 0.01), 5 m (5.74-9.49%, p = 0.006-0.04), 10 m (4.27-5.59%, p = 0.007-0.02), and 20 m (3.35-3.98%, p = 0.003-0.01). In conclusion, "composite" training is effective in enhancing fast stretch-shortening cycle efficiency inducing CMJ force and power augmentation. However, "composite" and sprint training are effective training approaches for enhancing maximal strength and sprint performance in a time efficient manner in hurling players.

Toxicokinetic evaluation of the common indoor air pollutant, α-pinene, and its potential reactive metabolite, α-pinene oxide, following inhalation exposure in rodents.

The toxicokinetic behavior of α-pinene and its potential reactive metabolite, α-pinene oxide, was investigated following whole body inhalation exposure to 50 and 100 ppm α-pinene in rats and mice for 6 h per day for 7d. In both species and sexes, the maximum blood concentration (Cmax) increased more than proportionally while the increase in area under the concentration time curve (AUC) was proportional to the exposure concentration. When normalized to the calculated dose (D), both Cmax/D (male rats, 12.2-54.5; female rats, 17.4-74.1; male mice, 7.41-14.2; female mice, 6.59-13.0 (ng/mL)/(mg/kg)) and AUC/D (male rats, 28.9-31.1; female rats, 55.8-56.8; male mice, 18.1-19.4; female mice, 19.2-22.5 (h*ng/mL)/(mg/kg)) in rats were higher than in mice and in female rats were higher than in male rats; no sex difference was observed in mice. α-Pinene was eliminated from blood with half-lives between 12.2 and 17.4 h in rats and 6.18-19.4 h in mice. At the low dose, the ratio of α-pinene oxide to α-pinene, based on Cmax and AUC, respectively, was 0.200-0.237 and 0.279-0.615 in rats and 0.060-0.086 and 0.036-0.011 in mice demonstrating lower formation of the oxide in mice than in rats. At the high dose, the ratio decreased considerably in both species pointing to saturation of pathways leading to the formation of α-pinene oxide. α-Pinene and the oxide were quantified in the mammary glands of rats and mice with tissue to blood ratios of ≥23 demonstrating retention of these analytes in mammary glands. The findings of epoxide formation and species- and sex-differences in systemic exposure may be important in providing context and relating animal findings to human exposures.

Acute Effects of "Composite" Training on Neuromuscular and Fast Stretch-Shortening Cycle Drop Jump Performance in Hurling Players.

ABSTRACT: Byrne, PJ, Moody, JA, Cooper, SM, and Kinsella, S. Acute effects of "composite" training on neuromuscular and fast stretch-shortening cycle drop jump performance in hurling players. J Strength Cond Res 35(12): 3474-3481, 2021-"Composite" training is a term developed by the authors and defined as the combination of a plyometric exercise with an explosive activity such as a sprint run, performed as a "combined repetition"/session. The purposes of this study were to investigate the acute effect of a "composite" training session on neuromuscular and fast stretch-shortening cycle bounce drop jumps (BDJs) in hurling players' immediately, after session, and after 7 days of recovery. Eight hurling players first completed a drop jump test to identify individual BDJ drop height, followed 72 hours later with a single "composite" training session. Three repetition maximum (3RM) back squat strength, BDJ, countermovement jump (CMJ), and sprint performance testing were performed 10 minutes before and immediately after session and 7 days after session. An analysis of variance reported a significant decrease in CMJ measures (height, velocity, and eccentric rate of force development) and sprint performance from presession to postsession (p ≤ 0.05). Moreover, a significant increase was evident for CMJ performance (height and power), sprint performance (5 and 20 m), 3RM back squat strength, and BDJ performance (reactive strength index and height) from postsession to post-7-day recovery (p ≤ 0.05). Pairwise comparisons indicated that absolute and relative 3RM strength significantly increased from presession to post-7 days (absolute 3RM: p = 0.0001; relative 3RM: p = 0.01). The findings indicate that "composite" training results in an immediate decline in CMJ measures after session possibly due to acute muscle fatigue, and supercompensation augments maximum lower-limb strength after 7 days of recovery.

Potentiating Response to Drop-Jump Protocols on Sprint Acceleration: Drop-Jump Volume and Intrarepetition Recovery Duration.

Byrne, PJ, Moody, JA, Cooper, SM, Callanan, D, and Kinsella, S. Potentiating response to drop-jump protocols on sprint acceleration: drop-jump volume and intrarepetition recovery duration. J Strength Cond Res 34(3): 717-727, 2020-The purpose of this study was to investigate the postactivation potentiation response first to bounce drop jump (BDJ) volume; second, BDJ intrarepetition recovery duration and recovery duration between BDJs and 20-meter (including 5- and 10-m split times) sprint performance. The study was undertaken in 2 parts, the first part compared different volumes of BDJs and the second part compared different BDJ intrarepetition recovery periods. The effect of recovery periods between the BDJs and the subsequent 20-m sprints was examined in both parts 1 and 2 (15 seconds, 4, 8, and 12 minutes). Fourteen (mean ± SD: age = 20.83 ± 1.26 years; height = 1.77 ± 0.04 m; and mass = 74.89 ± 6.07 kg) (part 1) and 15 (mean ± SD: age = 20.64 ± 1.00 years; height = 1.78 ± 0.06 m; and mass = 75.67 ± 6.28 kg) (part 2) male collegiate and club hurling players volunteered to participate. A randomized cross-over design was used to compare BDJ volumes (1, 2, and 3 sets of 3 repetitions) and BDJ intrarepetition recovery time (15 vs. 60 seconds) after a warm-up followed by 2 baseline 20-m sprints. The results in part 1 reported a significant improvement in 5- and 10-m sprint time for 1 set of 3 BDJs between baseline and 4 minutes (5 m: -2.34%, p = 0.04, effect size [ES] = -0.043; 10 m: -1.42%, p = 0.03, ES = -0.35), and baseline and 12 minutes (5 m: -3.33%, p = 0.03, ES = -0.57; 10 m: -2.13%, p = 0.01, ES = -0.52). Part 2 reported a significant improvement in 5-m sprint time between baseline and 15 seconds (5 m: -3.38%, p = 0.01, ES = -0.83; 10 m: -2.07%, p = 0.02, ES = -0.58) after the BDJs. The findings support the use of 1 set of 3 BDJs using a 15-second intrarepetition recovery period to maximize 5-, 10-, and 20-m sprint performance after 15 seconds of recovery after the final BDJ in hurling players. The acute response to this BDJ protocol proves to be time efficient and effective in acutely improving sprint acceleration.

The independent effects of hypovolaemia and pulmonary vasoconstriction on ventricular function and exercise capacity during acclimatisation to 3800 m.

KEY POINTS: We sought to determine the isolated and combined influence of hypovolaemia and hypoxic pulmonary vasoconstriction on the decrease in left ventricular (LV) function and maximal exercise capacity observed under hypobaric hypoxia. We performed echocardiography and maximal exercise tests at sea level (344 m), and following 5-10 days at the Barcroft Laboratory (3800 m; White Mountain, California) with and without (i) plasma volume expansion to sea level values and (ii) administration of the pulmonary vasodilatator sildenafil in a double-blinded and placebo-controlled trial. The high altitude-induced reduction in LV filling and ejection was abolished by plasma volume expansion but to a lesser extent by sildenafil administration; however, neither intervention had a positive effect on maximal exercise capacity. Both hypovolaemia and hypoxic pulmonary vasoconstriction play a role in the reduction of LV filling at 3800 m, but the increase in LV filling does not influence exercise capacity at this moderate altitude. ABSTRACT: We aimed to determine the isolated and combined contribution of hypovolaemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxaemia at high altitude. In a double-blinded, randomised and placebo-controlled design, 12 healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344 m) and after 5-10 days at 3800 m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of sildenafil (50 mg) to create four unique experimental conditions that were compared with SL values: high altitude (HA), Plasma Volume Expansion (HA-PVX), Sildenafil (HA-SIL) and Plasma Volume Expansion with Sildenafil (HA-PVX-SIL). High altitude exposure reduced plasma volume by 11% (P < 0.01) and increased pulmonary artery systolic pressure (19.6 ± 4.3 vs. 26.0 ± 5.4, P < 0.001); these differences were abolished by PVX and SIL respectively. LV end-diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA-PVX trial. LV EDV and SV were also elevated in the HA-SIL and HA-PVX-SIL trials compared to HA, but to a lesser extent. Neither PVX nor SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800 m both hypovolaemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, but restoring LV filling does not confer an improvement in maximal exercise performance.

Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents: A dose, species, and sex comparison.

Sulfolane is a ground water contaminant near refinery sites. The objective of this work was to investigate the toxicokinetics and bioavailability of sulfolane in male and female Harlan Hsd:Sprague Dawley® SD® rats and B6C3F1/N mice following a single oral administration of 10, 30, or 100 mg/kg. Sulfolane was rapidly absorbed in rats with the maximum plasma concentration, Cmax, reached at ≤1.47 h. Although Cmax increased proportionally to the dose, the half-life of elimination increased with the dose and the area under the concentration versus time curve (AUC) increased more than proportionally to the dose. In male and female rats, plasma elimination half-life increased with the dose from 1.97 to 6.33 h. Absorption of sulfolane in mice following oral administration was more rapid than in rats with Cmax reached at ≤0.55 h. In addition, mice had a shorter half-life (≤ 1.25 h) and a lower AUC than rats. In male and female mice, both Cmax and AUC increased more than proportionally to the dose. Bioavailability of sulfolane was higher in rats (81-83%) than mice (59-63%) at 10 mg/kg; at 30 and 100 mg/kg, bioavailability >100% in both species and sexes suggesting that the saturation of metabolism and clearance processes of sulfolane may begin at a single oral dose of ~30 mg/kg. There was no apparent sex difference in toxicokinetic parameters of sulfolane in rats and mice. These data demonstrate that sulfolane was well-absorbed following oral administration with high bioavailability in rats and mice with some species differences, but no sex difference.

Impact of secondary care financial incentives on the quality of physical healthcare for people with psychosis: a longitudinal controlled study.

BACKGROUND: Concerns have repeatedly been expressed about the quality of physical healthcare that people with psychosis receive. AIMS: To examine whether the introduction of a financial incentive for secondary care services led to improvements in the quality of physical healthcare for people with psychosis. METHOD: Longitudinal data were collected over an 8-year period on the quality of physical healthcare that people with psychosis received from 56 trusts in England before and after the introduction of the financial incentive. Control data were also collected from six health boards in Wales where a financial incentive was not introduced. We calculated the proportion of patients whose clinical records indicated that they had been screened for seven key aspects of physical health and whether they were offered interventions for problems identified during screening. RESULTS: Data from 17 947 people collected prior to (2011 and 2013) and following (2017) the introduction of the financial incentive in 2014 showed that the proportion of patients who received high-quality physical healthcare in England rose from 12.85% to 31.65% (difference 18.80, 95% CI 17.37-20.21). The proportion of patients who received high-quality physical healthcare in Wales during this period rose from 8.40% to 13.96% (difference 5.56, 95% CI 1.33-10.10). CONCLUSIONS: The results of this study suggest that financial incentives for secondary care mental health services are associated with marked improvements in the quality of care that patients receive. Further research is needed to examine their impact on aspects of care that are not incentivised.

Adaptation of myocardial twist in the remodelled athlete's heart is not related to cardiac output.

NEW FINDINGS: What is the central question of this study? What is the role of heart muscle function in the increased output of remodelled, larger hearts? What is the main finding and its importance? The greater stroke volume of endurance athletes is not associated with enhanced function of the heart muscle (i.e. left ventricular twist, torsion and twist-to-shortening) in normal and low-oxygen environments. These data indicate that, in the process of cardiac adaptation, left ventricular twist may play an important role that is not related to generating a larger output. Since enlarged hearts with low output can develop in disease, the present findings may influence the future interpretation of heart muscle function in patients. ABSTRACT: Despite increased stroke volume (SV), 'athlete's heart' has been proposed to have a similar left ventricular (LV) muscle function - as represented by LV twist - compared with the untrained state. However, the underpinning mechanisms and the associations between SV/cardiac output and LV twist during exercise are unknown. We hypothesised that endurance athletes would have a significantly lower twist-to-shortening ratio (TwSR, a parameter that relates twist to the shortening of heart muscle layers) at rest, but significantly greater LV muscle function during exercise. Eleven endurance trained male runners and 13 untrained males were tested at rest and during supine cycling exercise in normoxia and hypoxia (increased cardiac output but unaltered SV). Despite the expected cardiac remodelling in endurance athletes, LV twist, torsion, TwSR, strain and strain rate ('LV systolic mechanics') did not differ significantly between groups (P > 0.05). Structural remodelling, as per relative wall thickness, and LV twist did not correlate (r2  = 0.04, P = 0.33). In normoxia and hypoxia, exercise increased LV systolic mechanics in both groups (P < 0.001), but with different relationships to SV and cardiac output. Conversely to our hypothesis, hearts of different size had similar LV systolic mechanics, suggesting that similar twist, torsion and TwSR at rest and during exercise irrespective of cardiac output may be an important mechanism in healthy hearts. We hypothesise that the regulatory 'purpose' of LV twist may be related to the sensing of maximal cardiac myofibre stress, which may act as a biologically purposeful limiter to contraction.

A literature review of systemic to pulmonary collaterals in preterm infants to emphasise their existence and clinical importance.

AIM: Cardiorespiratory physiology plays an important role in neonatal care with increasing utility of point-of-care ultrasound. This review is to bring to light the importance of systemic to pulmonary collaterals (SPCs) in the preterm population without congenital heart disease (CHD) and provide a useful diagnostic tool to the neonatologist performing a cardiac ultrasound. METHODS: Medline, PubMed, EMBASE and the Internet were searched up to November 2017 for articles in English which included SPCs in preterm infants without CHD. This comprised title, abstract and full-text screening of relevant data. RESULTS: A total of 10 studies which included case reports, retrospective observational studies and one small prospective cohort study were identified and analysed in detail. The studies had varying focus such as variable incidence, clinical presentation, association with chronic lung disease, pathophysiology and clinical importance of SPCs. SPCs were overall thought to be prevalent, underdiagnosed and of clinical significance in preterm infants. CONCLUSION: Systemic to pulmonary collaterals are a potential left-to-right shunt in preterm infants and may contribute to worsening chronic lung disease (CLD) or heart failure. They should be carefully looked for when performing bedside cardiac ultrasound as the findings can mimic those seen in patent ductus arteriosus (PDA).

Rethinking cell-cycle-dependent gene expression in Schizosaccharomyces pombe.

Three studies of gene expression during the division cycle of Schizosaccharomyces pombe led to the proposal that a large number of genes are expressed at particular times during the S. pombe cell cycle. Yet only a small fraction of genes proposed to be expressed in a cell-cycle-dependent manner are reproducible in all three published studies. In addition to reproducibility problems, questions about expression amplitudes, cell-cycle timing of expression, synchronization artifacts, and the problem with methods for synchronizing cells must be considered. These problems and complications prompt the idea that caution should be used before accepting the conclusion that there are a large number of genes expressed in a cell-cycle-dependent manner in S. pombe.

Relationships between Cardiorespiratory and Muscular Fitness with Cardiometabolic Risk in Adolescents.

This study examined the independent relationships between cardiorespiratory and muscular fitness with cardiometabolic risk in adolescents. Subjects were 192 adolescents (118 boys), aged 15-17.5 years. The 2 m multi-stage fitness test assessed cardiorespiratory fitness and the counter movement jump assessed muscular fitness. Additional measures included interleukin-6, C-reactive protein, adiponectin, fibrinogen and plasminogen activator inhibitor-1. Regression analysis revealed that cardiorespiratory fitness was negatively related to cardiometabolic risk (ß = -0.014, p < 0.001). With additional adjustment for muscular fitness the relationship remained significant (ß = -0.015, p < 0.001). Muscular fitness was negatively related to cardiometabolic risk (ß = -0.021, p < 0.001) and remained significant after adjustment for cardiorespiratory fitness. Participants in the least-fit quartile for both cardiorespiratory and muscular fitness had significantly poorer cardiometabolic risk scores than those in the other quartiles. Findings revealed that muscular and cardiorespiratory fitness are significantly associated with cardiometabolic risk independently of one another.

A Palladium(II)-Catalyzed C-H Activation Cascade Sequence for Polyheterocycle Formation.

Polyheterocycles are found in many natural products and are useful moieties in functional materials and drug design. As part of a program towards the synthesis of Stemona alkaloids, a novel palladium(II)-catalyzed C-H activation strategy for the construction of such systems has been developed. Starting from simple 1,3-dienyl-substituted heterocycles, a large range of polycyclic systems containing pyrrole, indole, furan and thiophene moieties can be synthesized in a single step.

Parents' perceptions of genetics services for congenital heart disease: the role of demographic, clinical, and psychological factors in determining service attendance.

PURPOSE: We sought to identify the demographic, clinical, and psychological factors associated with parents' attendance at clinical genetics services for congenital heart disease. METHODS: A survey assessing access to cardiac genetics services and a range of other variables was sent to the families of 213 children diagnosed with congenital heart disease between the years 2000 and 2009 at the Sydney Children's Hospital, Australia. RESULTS: Of the 114 respondents, 22% had accessed cardiac genetics services. Variables strongly associated with service attendance included presence of a syndrome associated with congenital heart disease (odds ratio = 17.93; P < 0.001) and antenatal diagnosis of congenital heart disease (odds ratio = 4.13; P = 0.02). Most participants (87%) perceived genetic factors as "quite" or "extremely important" in the development of congenital heart disease, and many (73%) believed that receiving information about congenital heart disease and genetics was "quite" or "extremely important"; however, only 36% of participants could recall receiving information of this nature. Forty-two percent of parents reported current concerns about their child's health, and a substantial subset reported levels of depression (26%), anxiety (27%), and stress (32%) warranting clinical attention. CONCLUSION: There is a strong desire among parents of children with congenital heart disease for greater information about the role of genetic factors; however, most families do not access cardiac genetics services and report limited recall of information gathered from other sources.

Assessment and treatment of physical health problems among people with schizophrenia: national cross-sectional study.

BACKGROUND: In the UK and other high-income countries, life expectancy in people with schizophrenia is 20% lower than in the general population. AIMS: To examine the quality of assessment and treatment of physical health problems in people with schizophrenia. Method Retrospective audit of records of people with schizophrenia or schizoaffective disorder aged ⩾18. We collected data on nine key aspects of physical health for 5091 patients and combined these with a cross-sectional patient survey. RESULTS: Body mass index was recorded in 2599 (51.1%) patients during the previous 12 months and 1102 (21.6%) had evidence of assessment of all nine key measures. Among those with high blood sugar, there was recorded evidence of 53.5% receiving an appropriate intervention. Among those with dyslipidaemia, this was 19.9%. Despite this, most patients reported that they were satisfied with the physical healthcare they received. CONCLUSIONS: Assessment and treatment of common physical health problems in people with schizophrenia falls well below acceptable standards. Cooperation and communication between primary and secondary care services needs to improve if premature mortality in this group is to be reduced.

Clinical validation of a fast-acting acetaminophen: a randomized, active and placebo controlled dental pain study.

OBJECTIVES: To address the need for faster pain relief of over-the-counter (OTC) analgesic users, a novel drug delivery technology was developed to achieve faster absorption of orally administered acetaminophen with the goal of delivering earlier onset of pain relief. Previous development studies suggested that a 1000 mg dose of this fast-acting acetaminophen (FA-acetaminophen) formulation provided faster absorption and onset of action versus, commercially available OTC fast-acting analgesics, 1000 mg of extra-strength acetaminophen (ES-acetaminophen) or 400 mg of liquid-filled ibuprofen capsules (LG-ibuprofen). This study was designed as the definitive trial evaluating the onset of pain relief of FA-acetaminophen versus these same OTC comparators. METHODS: This single-dose, randomized, double-blind, placebo- and active-controlled clinical trial compared analgesic onset, overall efficacy, and safety of FA-acetaminophen 1000 mg, ES-acetaminophen 1000 mg, LG-ibuprofen 400 mg, and placebo over 4 h in a postsurgical dental pain model. Following removal of 3 to 4 impacted third molars, 664 subjects with moderate-to-severe pain were randomized in a 4:4:2:1 ratio to FA-acetaminophen (249), ES-acetaminophen (232), LG-ibuprofen (124), or placebo (59). Mean age was 18.9 years; 45.5% were male; 57.5% had severe baseline pain intensity. Subjects stopped a first stopwatch if/when they had perceptible pain relief and a second stopwatch if/when their pain relief became meaningful to them. Pain intensity difference (PID) and pain relief (PAR) were obtained using an 11-point numerical rating scale. FINDINGS: FA-acetaminophen 1000 mg had faster median time to onset of pain relief (15.7 min) compared to ES-acetaminophen 1000 mg (20.2 min, p = 0.035), LG-ibuprofen 400 mg (23.2 min, p < 0.001), and placebo (non-estimable), statistically greater mean PAR and PID scores than other treatment groups at 15 and 30 min, and a statistically greater percentage of subjects with confirmed perceptible pain relief at 15 and 20 min. At 25 min, FA-acetaminophen 1000 mg had a statistically significantly greater percentage of subjects with confirmed perceptible pain relief than LG-ibuprofen 400 mg and placebo. No clinically significant adverse events were reported. CONCLUSIONS: This study supports previous studies, demonstrating faster onset of analgesia with FA-acetaminophen 1000 mg compared to OTC ES-acetaminophen 1000 mg and OTC LG-ibuprofen 400 mg. CLINICALTRIALS.GOV IDENTIFIER: NCT03224403 https://clinicaltrials.gov/ct2/show/NCT03224403.

Development of novel calibration model(s) to predict whole-body density in professional football players.

INTRODUCTION: Questions continue to be raised about the validity that is in existence to estimate Db, in professional male footballer players. METHODS: Phase 1: n = 28 anthropometric variables were used on n = 206 footballers, using regression analyses to determine standard error of estimate and R2. A cut-off correlation coefficient set at r = 0.950 and 90% R2. Phase 2: all variables (z-scores, x- = 0.0, SD = ±1.0) to help reduce heteroscedasticity, ß, r, t, significance of t and P-values were calculated. Phase 3: a forced stepwise-backwards regression analysis approach with nine predictors which met the acceptance criteria (r = 0.950, R2 = 90% and ß weights) was used to develop a 'best fit' and a 'practical' calibration model. Phase 4: cross-validation of the two newly developed calibration method using LoA. RESULTS: The 'best fit' model SEM (0.115 g ml-1), the highest R2 (6.6%) (P ≤ 0.005), whereas the 'practical' calibration model SEM (0.115 g ml-1), R2 (4.7%) (P ≤ 0.005) with r values = 0.271 and 0.596 and R2 (%) coefficients = 0.3526 for the 'best fit' and 'practical' calibration models, respectively (P = 0.01). CONCLUSIONS: The two calibration models supported an ecologically and statistically valid contribution and can provide sound judgements about professional footballers' body composition.