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PubMed2001

Null hypothesis significance testing. On the survival of a flawed method.

Null hypothesis significance testing (NHST) is the researcher's workhorse for making inductive inferences. This method has often been challenged, has occasionally been defended, and has persistently been used through most of the history of scientific psychology. This article reviews both the criticisms of NHST and the arguments brought to its defense. The review shows that the criticisms address the logical validity of inferences arising from NHST, whereas the defenses stress the pragmatic value of these inferences. The author suggests that both critics and apologists implicitly rely on Bayesian assumptions. When these assumptions are made explicit, the primary challenge for NHST--and any system of induction--can be confronted. The challenge is to find a solution to the question of replicability.

Humans↗
PubMed2005

Effects of freshly neutralized aluminum on oxygen consumption by freshwater invertebrates.

The hypothesis tested in this study was if a pulse of precipitating aluminum (Al) at circumneutral pH covers the body of an invertebrate and, therefore, reduces the surface area available for respiration, organisms exposed to precipitating Al in an experimental system should consume less oxygen than organisms not exposed to aluminum. To test this hypothesis, experiments were conducted in the laboratory placing test organisms in biochemical oxygen demand (BOD) bottles containing a recently neutralized acidic, Al-enriched solution; conditions were meant to loosely mimic those of an acidic, Al-rich stream flowing into a larger, neutralizing receiving stream. The experiments suggested that freshly neutralized Al, i.e., Al in transition from ionic species in acidic waters to polymers or precipitating hydroxides after a rapid increase to pH > or = 6.8, impaired oxygen consumption by D. magna in a repeatable, dose-dependent fashion. Precipitating Al also impaired oxygen consumption by the perlid stoneflies Perlesta lagoi and Acroneuria abnormis, at the lower concentrations used, but higher concentrations resulted in oxygen consumption similar to that of controls. An ionoregulatory impairment response may explain this trend. Aluminum did not affect oxygen consumption by the larger, detritivorous stonefly, Pteronarcys pictetii.

Aluminum↗
PubMed2003

Bayesian inferences in the Cox model for order-restricted hypotheses.

In studying the relationship between an ordered categorical predictor and an event time, it is standard practice to include dichotomous indicators of the different levels of the predictor in a Cox model. One can then use a multiple degree-of-freedom score or partial likelihood ratio test for hypothesis testing. Often, interest focuses on comparing the null hypothesis of no difference to an order-restricted alternative, such as a monotone increase across levels of a predictor. This article proposes a Bayesian approach for addressing hypotheses of this type. We reparameterize the Cox model in terms of a cumulative product of parameters having conjugate prior densities, consisting of mixtures of point masses at one, and truncated gamma densities. Due to the structure of the model, posterior computation can proceed via a simple and efficient Gibbs sampling algorithm. Posterior probabilities for the global null hypothesis and subhypotheses, comparing the hazards for specific groups, can be calculated directly from the output of a single Gibbs chain. The approach allows for level sets across which a predictor has no effect. Generalizations to multiple predictors are described, and the method is applied to a study of emergency medical treatment for stroke.

Bayes Theorem↗
PubMed2005

Testing hypotheses of speciation timing in Dicamptodon copei and Dicamptodon aterrimus (Caudata: Dicamptodontidae).

Giant salamanders of the genus Dicamptodon are members of the mesic forest ecosystem that occurs in the Pacific Northwest of North America. We estimate the phylogeny of the genus to test several hypotheses concerning speciation and the origin of current species distributions. Specifically, we test competing a priori hypotheses of dispersal and vicariance to explain the disjunct inland distribution of the Idaho giant salamander (D. aterrimus) and to test the hypothesis of Pleistocene speciation of Cope's giant salamander (D. copei) using Bayesian hypothesis testing. We determined that available outgroups were too divergent to root the phylogeny effectively, and we calculated Bayesian posterior probabilities for each of the 15 possible root placements for this four-taxon group. This analysis placed the root on the branch leading to D. aterrimus, indicating that current distribution and speciation of D. aterrimus fit the ancient vicariance hypothesis and are attributable to the orogeny of the Cascade Mountains rather than recent inland dispersal. Furthermore, test results indicate that D. copei is distantly related to other coastal lineages and likely originated much earlier than the Pleistocene. These results suggest that speciation within the genus is attributable to ancient geologic events, while more recent Pleistocene glaciation has shaped genetic variation and distributions within the extant species.

Animals↗
PubMed1994

The analysis of 2 x 1 and 2 x 2 contingency tables: an historical review.

This paper describes the historical development of analytic techniques for frequency data presented as 2 x 1 or 2 x 2 contingency tables. The issues raised include: the need for a continuity correction when estimating the exceedance probability of a discrete statistic; the vulnerability of such statistics to a conservative bias when used in hypothesis testing; and the different statistical models that may underlie contingency tables. In the case of 2 x 1 contingency tables the recommended technique is the binomial test with a modified decision procedure for hypothesis testing. In the case of 2 x 2 contingency tables there is a single statistic approximating the chi-square distribution which can be used to test the hypothesis of an association between the two relevant variables and which in most practical situations is robust with respect to the occurrence of small expected cell frequencies.

Bias↗
PubMed1993

Exploratory data analysis in two-dimensional electrophoresis.

The use of computerized matching of proteins in the analysis of multiple two-dimensional electrophoresis (2DE) gels creates volumes of data that are readily accessible for exploratory analysis. When these data are used in health-effects studies or in studies to identify factors associated with particular diseases, hundreds or even thousands of hypotheses can be tested. Interpreting so many hypothesis tests requires some preliminary statistical evaluations of the data. In addition, prior to the preliminary statistical evaluations and subsequent hypothesis tests, accurate protein quantification and correct protein matching must be verified. In this report we present an approach used at the Centers for Disease Control to address these issues. This approach consists of a randomized experimental design incorporating replicate gels for each specimen, gel image analysis, protein matching, editing, Boolean unions of all gels to obtain correspondences and contradictions of match identification numbers, resolution of correspondences and contradictions, statistical tests to identify outliers, and finally an assessment of statistical and practical significance to focus attention on the proteins most likely to be associated with the effects under study. We illustrate our approach with data from an exploratory exposure-response study.

Blood Protein Electrophoresis↗
PubMed2006

Contraction stress and bond strength to dentinfor compatible and incompatible combinations of bonding systems and chemical and light-cured core build-up resin composites.

OBJECTIVE: Recent studies have shown that adhesives containing acidic monomers combined with composites can adversely effect the polymerization reaction producing low bond strengths. This phenomenon may also occur in making composite build-ups, jeopardizing one of the key factors for a successful core build-up restoration. The aim of this study was to investigate the contraction stress development and bond strength to dentin of core build-up resin composites combined with adhesives of various acidities. In addition the hypothesis tested was that light irradiation through chemical-cured composites during curing does not influence contraction stress or bond strength to dentin. METHODS: The chemical-cured (Clearfil Core) and light-cured (Clearfil Photo Core) core build-up resin composites were combined with two light-cured adhesives, Clearfil SE Bond (pH=1.8) and One-Step Bond (pH=4.3) and two dual-cured adhesives, Clearfil Photo Bond (pH=2.5) and All-Bond 2 (pH=6.1). Contraction stress development (at C=3) was determined for a period of 30 min in a universal testing machine where the opposing bonding surfaces were glass and dentin. After the 30 min period, the specimens were loaded in tension to determine the bond strength to dentin. To test the hypothesis, the combinations of the chemical-cured composites with the four bonding systems were also light irradiated for 40s right at the start of curing. RESULTS: For all composite-adhesive combinations tested, the adhesion to dentin resisted the developing polymerization contraction stresses. Both, dentin as a substrate to bond at and the use of adhesives, were showed to play an important role in keeping the contraction stresses low. The chemical-cured composite (Clearfil Core) combined with the light-cured adhesive SE Bond (pH=1.8) showed for both contraction stress and bond strength significant lower values than the other combinations. The hypothesis was accepted for combinations of the chemical-cured composite with All-Bond 2 and One-Step Bond, but was not supported by combinations with Clearfil SE Bond or Clearfil Photo Bond, as a significant increase in contraction stress was found. The higher values found for bond strength were not significant. SIGNIFICANCE: Besides combinations of chemical-cured core build-up composites with light or dual-cured adhesives as recommended by the manufacturer, also combinations with adhesives of other manufacturers are compatible, provided that the pH is higher than approximately 4.3. Chemical-cured core build-up composites combined with light-cured adhesives with a pH as low as 1.8 lead to a significantly lower stress and bond strength compared to other combinations. Light irradiation during curing through a combination of a chemical-cured composite and a low pH adhesive reactivates polymerization.

Acids↗
PubMed1983

Errors, Types I and II.

The practicing physician and the clinical investigator regularly confront therapeutic trials, diagnostic tests, and other hypothesis-testing situations. The clinical literature increasingly displays statistical notations and concepts related to decision making in medicine. For these reasons, the physician is obligated to have some familiarity with the principles behind the null hypothesis, Type I and II errors, statistical power, and related elements of hypothesis testing.

Clinical Laboratory Techniques↗
PubMed2000

The effects of alcoholic beverages on composite wear.

OBJECTIVES: In vivo wear of composite restorative materials appears to be, in part, dependent on various patient factors. Specifically, consumption of alcoholic beverages has the potential for increasing the degradation rate. The hypothesis tested in this experiment was that composite wear is dependent on the type of alcohol-containing liquid the materials are exposed to during three-body abrasive wear. METHODS: To test this hypothesis, composite wear experiments were performed using the ACTA three-body wear machine. Abrasive slurries containing either beer, wine, 9 vol% ethanol or water were used during the wear experiments. The data were analyzed using ANOVA and Tukey's test. RESULTS: The wine and ethanol solutions caused significantly more wear compared to the beer and water. There was no significant differences in the wear between the wine and 9 vol% ethanol groups, and the beer groups were not significantly different from the water groups. Furthermore, there was no significant interaction between the composite type and the various abrasive slurries. SIGNIFICANCE: These results indicate that alcoholic beverages with at least 9 vol% ethanol will increase the wear of composite. The observed increase in wear of composite by the wine was caused primarily by the ethanol content of the wine. Other constituents in the wine do not appear to have an effect on composite wear. The ethanol effect was consistent among different composite types.

Alcoholic Beverages↗
PubMed1993

Differential effects of diclofenac and aspirin on serum glutamic oxaloacetic transaminase elevations in patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To examine elevations in levels of serum glutamic oxaloacetic transaminase (SGOT) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) taking placebo, aspirin, or diclofenac, and to seek possible explanations for the occurrence of these elevations. METHODS: We conducted a meta-analysis of individual case reports from 3 RA protocols and 5 OA protocols, encompassing 814 diclofenac-treated patients, 443 aspirin-treated patients, and 359 placebo-treated patients. All of the RA protocols had nearly identical inclusion and exclusion criteria, as well as safety studies and followup; the same was true for the OA protocols. Analysis included correlation analysis and multiple linear and logistic regression, accounting for numerous potential confounding variables, with the SGOT as the dependent variable. F tests were used for hypothesis testing. RESULTS: By several analytic approaches, the principal determinants of SGOT concentrations were found to be baseline SGOT value, the use of aspirin in RA patients, and the use of diclofenac in OA patients. Other significant factors contributing to an increase in SGOT concentrations were duration of therapy and, perhaps, daily dosage (mg/lb). Hypothesis testing supported these results. Given a statistically average patient, we predicted a 1-2% chance of a mildly elevated SGOT level occurring among placebo-treated patients, a 6-7% chance among diclofenac- or aspirin-treated patients with RA, a 12% chance among diclofenac-treated patients with OA, and a 2% chance among aspirin-treated patients with OA. CONCLUSION: This study demonstrates a powerful method for performing meta-analysis, using available individual patient data to examine numerous factors that may affect an outcome of interest. In this case, mild elevations of SGOT were examined and found to be related to baseline SGOT levels, diclofenac use (in OA), and aspirin use (in RA). Of numerous other potential factors examined, including age, sex, alcohol use, concomitant medications, and concomitant diagnoses, only duration of therapy and, to a small extent, daily dosage, were also consistent determinants of SGOT elevation. The SGOT elevations were minimal and were not related to the occurrence of clinical hepatitis: No clinical hepatitis occurred.

Arthritis, Rheumatoid↗
PubMed1995

The effect of rider weight on rider-induced loads during common cycling situations.

Motivated by the desire to provide information useful in the design analysis of bicycle frames, the hypothesis tested was that a simple linear model would relate the maximum magnitudes of rider-induced loads to rider weight. Rider-induced loads are loads developed as a result of weight and muscular actions during pedalling. To test this hypothesis, five riders spanning a wide weight range rode a bicycle unrestrained on a treadmill. Dynamometers measured six components of pedal loads and five components of both seat and handlebar loads while riders rode three common cycling situations--seated cruising, seated climbing, and standing climbing. Average, average maximum, and average minimum values were computed for all load components and each was analyzed statistically. For all three test cases, the regression slope was significant for the force component normal to the pedal surface. Because the normal pedal force component has been shown previously to dominate frame stress at the point most likely to fatigue (Hull and Bolourchi, 1988, J. Strain. Anal. 23, 105-114), the results of this study should be useful in designing frames optimized for minimum weight and acceptable structural reliability.

Adult↗
PubMed1995

The effect of nutrition on testicular growth in mature Merino rams involves mechanisms that are independent of changes in GnRH pulse frequency.

In mature Merino rams, changes in diet to below or above the requirements for maintenance of body weight lead to changes in gonadotrophin secretion and testicular growth. However, the effects on testicular growth persist for much longer than those on LH and FSH secretion so that the gonadal and gonadotrophin responses are poorly correlated over time. This suggests that the gonadal effects may be partly independent of changes in the hypothalamic secretion of GnRH, an hypothesis tested in this study. In a short-term experiment (November, late spring, non-breeding season), we tested whether a high frequency of exogenous GnRH pulses could override the endogenous system and mimic the change in gonadotrophins seen in rams fed a high plane of nutrition. Mature Merino rams (scrotal circumference (mean +/- S.E.M.) 33.6 +/- 0.5 cm, body weight (mean +/- S.E.M.) 59.0 +/- 0.9 kg) were fed 900 g chaff + 1.6 kg lupin grain (High diet) or 360 g chaff + 60 g lupin grain (Low diet) and infused with 8 pulses of GnRH or saline daily for 5 weeks (n = 5/group). Blood was sampled every 20 min for 12 h on days-1 and 14 relative to the start of treatments. Relative to pre-treatment levels, LH pulse frequency and FSH concentrations were decreased on day 14 in saline-infused rams fed the Low diet and increased in saline-infused rams fed the High diet (P < 0.001). In GnRH-infused rams, gonadotrophin secretion was not affected by diet and the patterns of secretion of LH and FSH were similar to those in saline-infused rams fed the High diet. This model was used for a more complete endocrine analysis in a longer experiment designed to test the hypothesis that the effect of nutrition on testicular growth is partly independent of changes in the secretion of GnRH. The same treatments were imposed for 35 days on a different group of similar rams in March (autumn, mid-breeding season). Body weight and scrotal circumference were measured weekly and blood was sampled on days -1 and 14. On days -1 and 35, testosterone secretion in response to LH was tested by injecting exogenous ovine LH (NIADDK-oLH-25; 200 ng/kg body weight) to all rams. Body weight increased in rams fed the High diet and decreased in those fed the Low diet (P < 0.001) and was not affected by treatments as in experiment 1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1996

From cognition to biomechanics and back: the end-state comfort effect and the middle-is-faster effect.

Consistent preferences for particular types of movement suggest criteria for movement selection. These can be important when, as is usually the case, infinitely many movements allow a task to be achieved. The experiments reported here were designed to identify the source of a strong preference observed in earlier object-manipulation studies. In those earlier studies, subjects usually grabbed objects to be moved from one location to another in a way that afforded a comfortable final posture rather than a comfortable initial posture (the end-state comfort effect). The comfortable final state usually allowed the forearm to be at or near the middle of its range of motion on the pronation-supination dimension. The hypothesis tested here was that the end-state comfort effect stemmed from an expectation that movements can be made more quickly in the middle of the pronation-supination range than at either extreme. To test this hypothesis, we asked subjects, in the first experiment, to perform a handle rotation task that demanded little or no precision and so no need to make rapid to-and-fro homing-in movements near the end of the rotation. Half the subjects did not show the end-state comfort effect, in contrast to all previous studies, where all subjects showed the effect. An incidental finding of the first experiment was that handle rotations that ended at or near the end of the range of motion took longer than handle rotations that ended at or near the middle of the range of motion. To test the latter result more carefully, we asked subjects, in Experiments 2 and 3, to oscillate the forearm as quickly as possible, either in the supination part of the forearm rotation range, in the middle part of the range, or in the pronation part of the range. As predicted, oscillation frequencies were highest in midrange, and this was true for both hands. The results as a whole have implications for the relation between cognitive psychology and biomechanics, and for human factors.

Adult↗
PubMedDate not supplied

Analysing the effect of competition on general practitioners' behaviour using a multilevel modelling framework.

This paper examines the effect of competition on the behaviour of Australian general practitioners. The paper represents a considerable improvement on the methods of previous studies by using a random effects probit model in a multilevel modelling framework to obtain a more robust estimate of the effect of GP density, by including data on GP and practice characteristics and by using data with the actual GP consultation as the unit of observation which are disaggregated by medical condition. This latter characteristic enables us to test the hypothesis that the effect of competition varies across medical conditions. The main hypothesis tested is that GPs in areas of high competition are more likely to recommend a follow-up consultation compared to GPs in areas of low competition. The results suggest that the density of GPs influences the decision to follow up for one out of the four medical conditions analysed. However, there are other issues to be resolved before such results can be confidently interpreted as evidence of the effect of competition and as evidence of supplier-induced demand.

Adolescent↗
PubMed1984

Disposition of the manchette in the normal equine spermatid.

Bielanski and Kaczmarski (1979) reported the presence of microtubules in the neck region of mature stallion spermatozoa. It was hypothesized that these microtubules are derived from the manchette (a microtubular organelle present during spermiogenesis). In order to test this hypothesis, testes from 15 mature stallions were collected, perfused with 2% phosphate-buffered glutaraldehyde, and prepared for transmission electron microscopy. Spermatozoa from the caudae epididymides of each stallion were prepared in a similar manner. Spermiogenesis was observed in general, and the presence of a microtubular manchette was established in this species, juxtapositioned posterior to the nuclear ring and extending distally into the cytoplasmic collar which surrounds the prospective midpiece. Interlocking arms between the microtubules of the manchette were observed in transverse sections at all levels within the cytoplasmic collar before, during, and after caudal migration of the nuclear ring. Consequent to caudal migration of the nuclear ring and the annulus, as well as adluminal movement of the spermatid, the cytoplasmic collar was transformed into the residual cytoplasm. Within the residual cytoplasm, the manchette remained as a microtubular organelle which undergoes degeneration. The mature spermatozoa from the caudae epididymides of these stallions lacked the microtubules reported by Bielanski and Kaczmarski. The occurrence of such microtubules in the neck region of stallion spermatozoa is probably an abnormality.

Animals↗
PubMed1982

Hepatitis B virus and primary hepatocellular carcinoma: family studies in Korea.

Chronic infection with hepatitis B virus (HBV) is closely associated with the etio-pathogenesis of primary hepatocellular carcinoma (PHC). It has been proposed that infection with HBV early in life, frequently transmitted by an HBV-carrier mother, leads to persistent infection with HBV, which in turn is associated with the development of chronic active hepatitis (CAH), post-necrotic cirrhosis and PHC. If this view is correct, then there should be clustering of chronic carriers of HBV in families of patients with chronic liver disease. We tested this hypothesis in Korea by collecting serum from 132 patients with these chronic liver diseases admitted to the Seoul National University Hospital and 664 of their first-degree relatives. Controls (636) were members of two churches in Seoul and a rural village population; 261 of the controls were between the ages of 30 and 59, the age range that included 95% of the cases of chronic liver disease. Sera were assayed for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). Almost all cases showed evidence of present or past infection with HBV; 80% were HBsAg(+) and 14% were anti-HBs(+); 100% of 47 cases of PHC, 100% of 35 cases of cirrhosis, and 94% of 50 cases of CAH were anti-HBc(+); 6% of males and 4% of females in control population (30-59 years of age) were HBsAg(+), 71% were anti-HBc(+), and 51% were anti-HBs(+). HBsAg(+) patients with chronic liver disease tended to be younger than HBsAg(-) patients with anti-HBs or anti-HBc antibodies. Mothers of patients with more frequently (HBsAg(+) (9 of 33) than age-matched women in the control population (0 of 34) or wives of patients (5 of 68). Five of 23 fathers were also HBsAg(+) compared with 1 of 25 age-matched controls. As first observed in Africa, there was a deficit of anti-HBs in the fathers of cases compared with the controls. Siblings of patients were frequently HBsAg(+) (45% of 154), with the highest prevalence in brothers (53%). Family history shows that five fathers, two mothers and five brothers of cases have died of PHC. These data are compatible with the hypothesis tested and lend further support to the view that prevention of infection with HBV will lead to a marked decrease in the incidence of CAH, cirrhosis and PHC in areas where these diseases are endemic. Members of the families of patients with these diseases are at high risk of developing persistent infection with HBV and chronic liver disease. It would be appropriate to focus preventive strategies on infants and children in such families.

Africa↗
PubMed2004

Role of basic helix-loop-helix (bHLH) and CREB transcription factors in the regulation of Sertoli cell androgen-binding protein expression.

Differentiation of Sertoli cells is marked by the presence of novel gene products such as transferrin and androgen-binding protein (ABP). Transcriptional regulation of Sertoli cell differentiation is, in part, controlled through the binding of specific transcription factors to response elements within these genes promoters. Transferrin gene expression has been shown to be regulated by the binding and interactions of basic helix-loop-helix (bHLH) and cAMP response element binding protein (CREB) to an E-box and cyclic AMP response element (CRE), respectively. Interaction between the bHLH and CREB is facilitated through subsequent binding of CREB-binding protein (CBP)/p300. The hypothesis tested in the current study is that ABP expression is regulated by a similar mechanism. The ABP promoter activation was analyzed through the use of transfection assays, site-directed mutagenesis, and electromobility shift assays (EMSA). Transient transfections of rat Sertoli cells used a reporter construct containing the proximal 619 bp of the ABP promoter. Observations suggest that cAMP and follicle stimulating hormone (FSH) upregulate the expression of ABP. Mutational studies of the three E-boxes and the CRE of the 619-bp ABP promoter indicate that all of these elements are critical for stimulation of promoter activity. EMSA revealed a weak interaction between an E-box-2 and the CRE that are overlapping in the promoter. An artificial promoter that contains only an E-box and CRE was created to further test this hypothesis. The artificial promoter was stimulated by both FSH and cAMP. Experiments with mutants of the artificial promoter demonstrate that both response elements contribute to the optimal activation of the promoter construct. The overexpression of the bHLH inhibitor Id (i.e., inhibitor of differentiation) that binds bHLH proteins and eliminates DNA binding was found to suppress hormone activation of the ABP promoter. Combined observations of the ABP promoter and artificial promoter provide insight into a common mechanism for gene regulation in differentiated Sertoli cells involving a role for both the bHLH and CREB family of transcription factors.

Androgen-Binding Protein↗
PubMed1993

Response of intersegmental knee loads to foot/pedal platform degrees of freedom in cycling.

The hypothesis tested in this article was that the three-dimensional intersegmental knee loads would be reduced in cycling by foot/pedal platforms which permitted relative motion between the foot and pedal. To test this hypothesis, pedal load and lower limb kinematic data were collected from 11 subjects who pedaled with four foot/pedal platforms mounted on a six-load-component dynamometer. One of the four platforms did not allow any relative foot/pedal movement while the other three permitted either medial/lateral translation, adduction/abduction rotation or inversion/eversion rotation. Three-dimensional intersegmental knee loads were computed for each of the four platforms using a previously reported biomechanical model. A number of quantities describing each of the intersegmental knee load components was computed and compared using analysis of variance techniques. The key results were that the medial/lateral translation platform did not cause significant differences in intersegmental knee load quantities relative to those for the fixed platform. However, both of the platforms permitting rotations significantly reduced many but did not significantly increase any intersegmental knee load quantities. Of these two platforms, the abduction/abduction platform significantly reduced both the axial and varus/valgus knee moments while the inversion/eversion platform significantly reduced only varus/valgus moments. These results have application to bicycle pedal design where the goal is to reduce intersegmental knee loads, hence possibly alleviating overuse knee injuries.

Bicycling↗