Bayesian strategy selection identifies optimal solutions to complex problems using an example from GP prescribing.

Complex health problems require multi-strategy, multi-target interventions. We present a method that uses machine learning techniques to choose optimal interventions from a set of possible interventions within a case study aiming to increase General Practitioner (GP) discussions of physical activity (PA) with their patients. Interventions were developed based on a causal loop diagram with 26 GPs across 13 clinics in Geelong, Australia. GPs prioritised eight from more than 80 potential interventions to increase GP discussion of PA with patients. Following a 2-week baseline, a multi-arm bandit algorithm was used to assign optimal strategies to GP clinics with the target outcome being GP PA discussion rates. The algorithm was updated weekly and the process iterated until the more promising strategies emerged (a duration of seven weeks). The top three performing strategies were continued for 3 weeks to improve the power of the hypothesis test of effectiveness for each strategy compared to baseline. GPs recorded a total of 11,176 conversations about PA. GPs identified 15 factors affecting GP PA discussion rates with patients including GP skills and awareness, fragmentation of care and fear of adverse outcomes. The two most effective strategies were correctly identified within seven weeks of the algorithm-based assignment of strategies. These were clinic reception staff providing PA information to patients at check in and PA screening questionnaires completed in the waiting room. This study demonstrates an efficient way to test and identify optimal strategies from multiple possible solutions.

Decreased incidence of knee posterior cruciate ligament injury in Australian Football League after ruck rule change.

OBJECTIVE: To assess whether a rule change introduced in the Australian Football League (AFL) before the start of the 2005 season, to limit the run-up of ruckmen at the centre bounce, has been successful in reducing the incidence of knee posterior cruciate ligament (PCL) injuries. DESIGN: Cohort study with historical control. SETTING: The AFL competition from 1992 to 2008 inclusive. ASSESSMENT OF RISK FACTORS: The presence of a rule change (four seasons) compared with the previous 13 seasons (divided into two eras of seven and six seasons). MAIN OUTCOME MEASURE: Occurrence of knee PCL injury during a regular season or finals match, both from all causes and specifically from centre bounce ruck collision mechanisms. RESULTS: From 1992 to 1998 there were 11.0 PCL injuries per 10,000 player-hours, with 0.8 ruck injuries per 10,000 centre bounces. From 1999 to 2004, the rates increased to 12.9 per 10,000 player-hours and 5.6 ruck injuries per 10,000 centre bounces (p<0.01). The rates reduced to 5.9 PCL injuries per 10,000 player-hours and 0.9 ruck injuries per 10,000 centre bounces in the period 2005-2008 following the rule change (p<0.01). There was a lower relative risk in 2005-2008 than in 1999-2004 of incurring a centre bounce ruck PCL injury (0.16 (95% CI 0.04 to 0.69)) or of sustaining any PCL injury (0.45 (95% CI 0.28 to 0.75)). CONCLUSION: A rule change in the AFL to limit the run-up of ruckmen at the centre bounce has successfully reduced the rate of PCL injuries with this mechanism, with the total incidence of PCL injuries also falling.

CYP121, CYP51 and associated redox systems in Mycobacterium tuberculosis: towards deconvoluting enzymology of P450 systems in a human pathogen.

An extraordinary array of P450 (cytochrome P450) enzymes are encoded on the genome of the human pathogen Mycobacterium tuberculosis (Mtb) and in related mycobacteria and actinobacteria. These include the first characterized sterol 14alpha-demethylase P450 (CYP51), a known target for azole and triazole drugs in yeasts and fungi. To date, only two Mtb P450s have been characterized in detail: CYP51 and CYP121. The CYP121 P450 shows structural relationships with P450 enzymes involved in synthesis of polyketide antibiotics. Both P450s exhibit tight binding to a range of azole drugs (e.g. clotrimazole and fluconazole) and the same drugs also have potent effects on growth of mycobacteria (but not of e.g. Escherichia coli). Atomic structures are available for both Mtb CYP51 and CYP121, revealing modes of azole binding and intriguing mechanistic and structural aspects. This paper reviews our current knowledge of these and the other P450 systems in Mtb including recent data relating to the reversible conversion of the CYP51 enzyme between P450 (thiolate-co-ordinated) and P420 (thiol-co-ordinated) species on reduction of the haem iron in the absence of a P450 substrate. The accessory flavoprotein and iron-sulfur proteins required to drive P450 catalysis are also discussed, providing an overview of the current state of knowledge of Mtb P450 redox systems.

Rye grass is associated with fewer non-contact anterior cruciate ligament injuries than bermuda grass.

OBJECTIVE: To assess the contribution of ground variables including grass type to the rate of anterior cruciate ligament (ACL) injury in the Australian Football League (AFL), specifically which factors are primarily responsible for previously observed warm season and early season biases for ACL injuries. METHODS: Grass types used at the major AFL venues from 1992 to 2004 were established by consultation with ground managers, and ground hardness and other weather variables were measured prospectively. RESULTS: There were 115 ACL injuries occurring in matches during the survey time period, 88 with a non-contact mechanism. In multivariate analysis, use of bermuda (couch) grass as opposed to rye grass, higher grade of match, and earlier stage of the season were independent risk factors for non-contact ACL injury. Ground hardness readings did not show a significant association with ACL injury risk, whereas weather variables of high evaporation and low prior rainfall showed univariate association with injury risk but could not be entered into a logistic regression equation. DISCUSSION: Rye grass appears to offer protection against ACL injury compared with bermuda (couch) grass fields. The likely mechanism is reduced "trapping" of football boots by less thatch. Grass species as a single consideration cannot fully explain the ACL early season bias, but is probably responsible for the warm season bias seen in the AFL. Weather variables previously identified as predictors are probably markers for predominance of bermuda over rye grass in mixed fields.

Flavocytochrome P450 BM3: an update on structure and mechanism of a biotechnologically important enzyme.

Since its discovery in the 1980s, the fatty acid hydroxylase flavocytochrome P450 (cytochrome P450) BM3 (CYP102A1) from Bacillus megaterium has been adopted as a paradigm for the understanding of structure and mechanism in the P450 superfamily of enzymes. P450 BM3 was the first P450 discovered as a fusion to its redox partner--a eukaryotic-like diflavin reductase. This fact fuelled the interest in soluble P450 BM3 as a model for the mammalian hepatic P450 enzymes, which operate a similar electron transport chain using separate, membrane-embedded P450 and reductase enzymes. Structures of each of the component domains of P450 BM3 have now been resolved and detailed protein engineering and molecular enzymology studies have established roles for several amino acids in, e.g. substrate binding, coenzyme selectivity and catalysis. The potential of P450 BM3 for biotechnological applications has also been recognized, with variants capable of industrially important transformations generated using rational mutagenesis and forced evolution techniques. This paper focuses on recent developments in our understanding of structure and mechanism of this important enzyme and highlights important problems still to be resolved.

The playing habits and other commitments of elite junior Australian football players.

The Victorian Football League Under 18 (VFL U18) competition provides a pathway to the elite senior level of Australian football. Players involved in the VFL U18 competition also play football in other contexts, including for school and local clubs, and can have considerable additional work and educational demands. A total of 103 elite junior Australian football players from six VFL U18 clubs participated in a survey that asked about their football playing habits and other commitments. The median age of players when they first joined their VFL U18 squad was 16.3 years. The players participated in a median of five weekly training sessions during the last two weeks of the 1999 preseason and played a median of five preseason games. Fifty percent of the players expected to participate in 3-4 training sessions per week and 25% expected to play more than two games per week during the 1999 season. Half of the players reported ambitions to play Australian Football League (AFL) football. Further research is needed to determine whether or not high participation levels have negative impacts on performance and injury risk in these players.

Epidemiology of injuries in the Australian Football League, seasons 1997-2000.

OBJECTIVE: To describe the epidemiology of injuries in the Australian Football League (AFL) over four seasons. METHODS: An injury was defined as "any physical or medical condition that caused a player to miss a match in the regular season." The rationale for this definition was to eliminate a previously noted tendency of team recorders to interpret injury definitions subjectively. Administrative records of injury payments to players who did not play matches determined the occurrence of an injury. RESULTS: The seasonal incidence of new injuries was 39 per club (of 40 players) per season (of 22 matches). The match injury incidence for AFL games was 25.7 injuries per 1000 player hours. The injury prevalence (percentage of players missing through injury in an average week) was 16%. The recurrence rate of injuries was 17%. The most common and prevalent injury was hamstring strain (six injuries per club per season, resulting in 21 missed matches per club per season), followed in prevalence by anterior cruciate ligament and groin injuries. CONCLUSIONS: The injury definition of this study does not produce incidence rates that are complete for all minor injuries. However, the determination of an injury is made by a single entity in exactly the same manner for all teams, which overcomes a significant methodological flaw present in other multiteam injury surveillance systems.

1998 European Cataract Outcome Study: report from the European Cataract Outcome Study Group.

PURPOSE: To collect clinical data on cataract surgery to allow participating surgeons to compare their performance with that of their colleagues in an anonymous manner. SETTING: Surgeons from 31 surgical units providing cataract surgery in 13 European countries. METHODS: Every patient at each participating unit having surgery during 1 study month was evaluated. Data were reported to the coordinating center at the time of surgery and at the final examination. When the study was closed 6 months after surgery, all participants were provided with the outcomes from their own patients so they could compare them with outcomes from other centers. RESULTS: The study included preoperative and intraoperative data on 2950 patients. Complete follow-up data were available for 2731 patients. The surgical audit included surgically induced astigmatism, proximity of target refraction, and the frequency of major complications. For each variable, a large variation in outcome between participating centers was found. Most centers had results both above and below average for different variables. CONCLUSION: Cataract surgery data collected from 31 units in 13 European countries allowed participants to compare their performance with that of their colleagues in an anonymous manner. Significant variation was found in the outcomes among the units, with many units reporting results above and below the averages.

Intrinsic and extrinsic risk factors for anterior cruciate ligament injury in Australian footballers.

The aim of this study was to examine the interaction between intrinsic (player-related) and extrinsic (environment-related) variables as risk factors for anterior cruciate ligament injury in Australian football. Between 1992 and 1999, 100,820 player-match exposures were analyzed for risk of anterior cruciate ligament injury using logistic regression analysis. There were 63 surgically proven noncontact anterior cruciate ligament injuries. The strongest risk factors were a player history of anterior cruciate ligament reconstruction either in the previous 12 months (relative risk [RR], 11.33; 95% confidence interval [CI], 4.02 to 31.91) or before the previous 12 months (RR, 4.44; 95% CI, 2.46 to 8.01). Weather conditions that were associated with dry field conditions--high water evaporation in the month before the match (RR, 2.55; 95% CI, 1.44 to 4.52) and low rainfall in the year before the match (RR, 2.87; 95% CI, 1.30 to 6.32)--were also significantly associated with these injuries. The increased risk of injury in the first 12 months after reconstruction was associated with the reconstructed knee, whereas after 12 months there was an even distribution of new injuries to the reconstructed knee and contralateral knee. A history of anterior cruciate ligament reconstruction is a risk factor for further injury. Weather conditions of high evaporation and low rainfall before matches are associated with noncontact anterior cruciate ligament injury.

Comparing wobble board and jump-landing training effects on knee and ankle movement discrimination.

The effects of two training programs on movement discrimination ability, at the ankle and knee, were assessed from the left and right lower limbs of forty-four football players. All players in three Under 18 Victorian Football League (VFL) squads were allocated to either wobble board training, jump landing training, or no-training conditions. Pre-tests to assess discrimination of extent for active movements made while standing were carried out on both ankles and knees of all subjects, using an automated device to accurately set the different movement stop points. Five distances were used, between 10.5 degrees and 14.5 degrees from horizontal for ankle inversion, and between 30.3 degrees and 31.7 degrees from vertical for knee flexion. From a series of 50 inversion movements and 50 knee flexion movements, matrices of absolute judgement by actual movement extent were produced. Non-parametric signal detection analysis was applied to the discrimination score. All subjects were retested after eight weeks. Improvement in discrimination of ankle movements into inversion from pre-test (0.65) to post test (0.70) for the wobble board trained group was significantly larger than the change in the jump-landing trained and the untrained groups (Jump Landing: Pretest: 0.64 to Post-test: 0.64 and Control; Pretest: 0.63 to Post-test: 0.64). Discrimination of knee flexion movements improved significantly from pre-test to post-test in all three groups. These data demonstrate that wobble board training can improve discrimination of discrete ankle inversion movements, an effect interpreted as enabling greater accuracy in the making of inversion movements in foot preparation prior to ground contact.

Rainfall, evaporation and the risk of non-contact anterior cruciate ligament injury in the Australian Football League.

OBJECTIVE: To determine if weather conditions affect the risk of anterior cruciate ligament (ACL) tear in Australian Football. DESIGN: Prospective observational analytic study of football matches. SETTING: The Australian Football League (AFL), a professional competition. PARTICIPANTS: All players in 2280 matches from 1992-1998. MAIN OUTCOME MEASURES: Surgically-proven ACL injury, not involving a direct contact mechanism, during a match; rainfall; water evaporation. RESULTS: 59 ACL injuries not involving direct contact occurred during the study period, more commonly in cities north of Melbourne (chi 2 = 17.0; df = 1; P < 0.001). Senior grade matches (relative risk [RR], 3.03; 95% confidence interval [CI], 1.52-6.03), high water evaporation in the month before the match (RR, 2.80; 95% CI, 1.53-5.10) and low rainfall in the year before the match (RR, 1.93; 95% CI, 1.12-3.34) were significantly associated with these injuries. CONCLUSION: Low water evaporation and high rainfall significantly lower the risk of ACL injuries in AFL footballers. The likely mechanism is a softening of the ground, which lowers shoe-surface traction. Consistent extra watering and covering of grounds during periods of high water evaporation may lower the rate of ACL injuries.

Comparison of injuries in elite senior and junior Australian football.

Three thousand and thirty one AFL and 1034 injuries in the VSFL U/18 competition were recorded by club doctors over the 1992, 1993 and 1994 seasons. Hamstring strains had the highest incidence (86.4 per 10,000 player hours) and prevalence (30.2 hours missed per 1000 hours) of any injury in the AFL, but were significantly less common in the U/18 competition. Other injuries which were common in both competitions were ankle sprains, thigh haematomas, concussion, groin strains and head lacerations. Injury prevalence was higher overall in the AFL, with lower limb muscle strains (hamstring, calf, quadriceps) being significantly more prevalent than in the U/18 competition. Injuries which were significantly more prevalent in the U/18 competition included stress fractures and concussion. Subsequent to this study, coaches and medical staff in the U/18 competition were made aware of the high risk of stress fractures in young footballers with heavy training loads. The AFL injury survey is ongoing and in the process of being computerised; risk factors for specific injuries with high rates are being studied further.