Endometriosis: A review of recent evidence and guidelines.

BACKGROUND: Endometriosis is a chronic inflammatory condition defined as endometrial-like tissue proliferating outside the uterus. It is a common yet frequently under-recognised condition affecting one in nine Australian women. OBJECTIVE: This paper aims to provide a summary of the recommendations for the diagnosis and management of endometriosis-associated pain and infertility from the most recent evidence-based guidelines on endometriosis by the European Society of Human Reproduction and Embryology, the Royal Australian College of Obstetricians and Gynaecologists and the National Institute for Health and Care Excellence. DISCUSSION: Effective management of endometriosis requires prompt diagnosis to enable early multidisciplinary intervention that aligns with patient needs and priorities. Assessment includes a thorough history, pelvic examination where appropriate and referral for transvaginal ultrasound and/or magnetic resonance imaging. If endometriosis is suspected based on clinical symptoms but imaging is negative or empirical treatment is ineffective, individuals should be referred to a gynaecologist for further assessment and consideration of laparoscopy. Management options include hormonal and surgical therapies.

The Long Goodbye: Finally Moving on from the Relative Potency Approach to a Mixtures Approach for Polycyclic Aromatic Hydrocarbons (PAHs).

For the past several decades, a relative potency approach has been used to estimate the human health risks from exposure to polycyclic aromatic hydrocarbon (PAH) mixtures. Risk estimates are derived using potency equivalence factors (PEFs; also called relative potency factors [RPFs]), based on the ratio of selected PAHs to benzo[a]pyrene (BaP), expressed qualitatively by orders of magnitude. To quantify PEFs for 18 selected carcinogenic PAHs, a systematic approach with a priori and dose response criteria was developed, building on draft work by the US EPA in 2010 and its review by US EPA Science Advisory Board (SAB) in 2011. An exhaustive search for carcinogenicity studies that included both target PAHs and BaP with environmentally relevant exposure routes found only 48 animal bioassay datasets (mostly pre-1992 based on skin painting). Only eight datasets provided adequate low-response data, and of these only four datasets were appropriate for modeling to estimate PEFs; only benzo[b]fluoranthene and cyclopenta[c,d]pyrene had a PEF that could be quantified. Thus, current knowledge of PAH carcinogenicity is insufficient to support quantitative PEFs for PAH mixtures. This highlights the long-acknowledged need for an interdisciplinary approach to estimate risks from PAH mixtures. Use of alternative and short-term toxicity testing methods, improved mixture characterization, understanding the fate and bioavailability of PAH mixtures, and understanding exposure route-related differences in carcinogenicity are discussed as ways to improve the understanding of the risks of PAHs.

Patient journey following lumbar discectomy surgery: protocol for a single-centre qualitative analysis of the patient rehabilitation experience (DiscJourn).

INTRODUCTION: Lumbar discectomy is a widely used surgical procedure internationally with the majority of patients experiencing significant benefit. However, approximately 20% of patients report suboptimal functional recovery and quality of life. The impact and meaning of the surgical experience from the patients' perspective are not fully understood. Furthermore, there is limited evidence guiding postoperative management with significant clinical practice variation and it is unclear if current postoperative support is valued, beneficial or meets patients' needs and expectations. This study aims to address the evidence gap by moving beyond current knowledge to gain insight into the lived experiences relating to patients' lumbar discectomy surgery journey. Results will inform more meaningful and specific care, thus, enhance rehabilitation and outcomes. METHODS AND ANALYSIS: A qualitative investigation using interpretative phenomenology analysis (IPA) will provide a flexible inductive research approach. A purposive sample (n=20) of patients undergoing primary discectomy will be recruited from one UK NHS secondary care centre. Semi-structured interviews will be conducted postsurgery discharge. A topic guide, developed from the literature and our previous work with input from two patient co-investigators, will guide interviews with the flexibility to explore interesting or patient-specific points raised. Providing longitudinal data, patients will keep weekly diaries capturing experiences and change over time throughout 12 months following surgery. A second interview will be completed 1 year postsurgery with its topic guide informed by initial findings. This combination of patient interviews and diaries will capture patients' attitudes and beliefs regarding surgery and recovery, facilitators and barriers to progress, experiences regarding return to activities/function and interactions with healthcare professionals. The rich density of data will be thematically analysed in accordance with IPA, supported by NVivo software. ETHICS AND DISSEMINATION: Ethical approval has been granted by the London-Bloomsbury Research Ethics Committee (18/LO/0459; IRAS 241345). Conclusions will be disseminated through conferences and peer-reviewed journals.

Patient and physiotherapist perceptions of rehabilitation following primary lumbar discectomy: a qualitative focus group study embedded within an external pilot and feasibility trial.

OBJECTIVE: To evaluate patients' and physiotherapists' perceptions, preferences and feelings about rehabilitation following lumbar discectomy surgery. DESIGN: A qualitative focus group study, informed from the theoretical perspective of phenomenology, of patients' and physiotherapists' experiences of rehabilitation following lumbar discectomy was conducted. The focus groups were used to explore patients' and physiotherapists' perceptions and their preferences and feelings about different approaches to rehabilitation. The focus groups were facilitated and observed by experienced researchers and were informed by a topic guide that had been piloted previously. SETTING: The study was embedded within an external pilot and feasibility trial that randomised patients across two secondary care spinal surgery sites in the UK to receive either 1:1 physiotherapy and leaflet or leaflet-only interventions. PARTICIPANTS: Five focus groups took place between April and July 2014. A framework analysis of thematic coding (deductive and inductive components) by two researchers captured identified themes common to both patients and physiotherapists. Data from three focus groups with patients and carers (n=11) and two with physiotherapists (n=15) contributed to the analytic framework. RESULTS: Emerging themes included: the value of patient leaflets with or without physiotherapy interventions; the importance of self-motivation in the recovery pathway; benefits of group physiotherapy for some patient groups and patient preference influencing rehabilitation. CONCLUSION: Patients and physiotherapists perceived the study patient leaflet and 1:1 physiotherapy interventions as high quality and valuable. Patients' personal priorities, for example, their need to return to work, influenced their preferences for rehabilitation interventions following surgery.

First stage of labour management practices: A survey of Australian obstetric providers.

AIMS: To report on the opinions and reported practices of Australian obstetricians and general practice (GP) obstetricians, in the definition and management of spontaneous first stage of labour, in low-risk nulliparous women. MATERIALS AND METHODS: Cross-sectional survey sent electronically to all Australian Specialist obstetricians (FRANZCOG) and Diplomates. Respondents answered questions regarding care of nulliparous women in spontaneous labour at term across three domains: (i) practitioners' characteristics; (ii) current practice; (iii) opinion regarding joint statement by ACOG/SMFM (Society of Maternal Fetal Medicine) 'Safe prevention of primary caesarean section'. RESULTS: The dataset included responses from 664 participants, representing 29% of Specialists and 11% of Diplomates. Responses varied in the criteria used to define normal labour, and the diagnosis and management of prolonged labour. Clinicians with more post-qualification experience considered the minimal acceptable progress to be faster than those with fewer years of experience (P = 0.02). Clinicians working in higher acuity hospitals were more likely to augment labour for longer prior to recommending a caesarean section for active phase arrest, compared to those in lower acuity hospitals (P = 0.025). The majority of respondents (58.2%) already based their practice on the ACOG/SMFM 'Safe prevention of primary caesarean section' statement, or would now consider changing their practice. CONCLUSION: There is a lack of consensus among Australian obstetricians and GP obstetricians regarding definition of normal progress in first stage of labour and how to manage abnormal progress; however, many are open to new recommendations for practice.

Knowledge acquisition and research evidence in autism: Researcher and practitioner perspectives and engagement.

BACKGROUND: Government policy and national practice guidelines have created an increasing need for autism services to adopt an evidence-based practice approach. However, a gap continues to exist between research evidence and its application. This study investigated the difference between autism researchers and practitioners in their methods of acquiring knowledge. METHODS: In a questionnaire study, 261 practitioners and 422 researchers reported on the methods they use and perceive to be beneficial for increasing research access and knowledge. They also reported on their level of engagement with members of the other professional community. RESULTS: Researchers and practitioners reported different methods used to access information. Each group, however, had similar overall priorities regarding access to research information. While researchers endorsed the use of academic journals significantly more often than practitioners, both groups included academic journals in their top three choices. The groups differed in the levels of engagement they reported; researchers indicated they were more engaged with practitioners than vice versa. CONCLUSIONS: Comparison of researcher and practitioner preferences led to several recommendations to improve knowledge sharing and translation, including enhancing access to original research publications, facilitating informal networking opportunities and the development of proposals for the inclusion of practitioners throughout the research process.

Physiotherapy Post Lumbar Discectomy: Prospective Feasibility and Pilot Randomised Controlled Trial.

OBJECTIVES: To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components. DESIGN AND SETTING: A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres. PARTICIPANTS: Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy. INTERVENTIONS: Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone. MAIN OUTCOME MEASURES: Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation. RESULTS: At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI -9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported. CONCLUSIONS: Both interventions were acceptable, and it is promising that they both demonstrated a trend in reducing disability in this population. A randomised controlled trial, using a different trial design, is needed to ascertain the effectiveness of combining the interventions into a stepped care intervention and comparing to a no intervention arm. Findings will guide design changes for an adequately powered randomised controlled trial, using RMDQ as the primary outcome. TRIAL REGISTRATION: ISRCTN registry 33808269.

Evaluation of current surgeon practice for patients undergoing lumbar spinal fusion surgery in the United Kingdom.

AIM: To ascertain current surgeon practice in the United Kingdom National Health Service for the management of patients undergoing lumbar spinal fusion surgery. METHODS: Descriptive survey methodology utilised an online questionnaire administered through SurveyMonkey. Eligible participants were all surgeons currently carrying out lumbar spinal fusion surgery in the National Health Service. Two previous surveys and a recent systematic review informed questions. Statistical analyses included responder characteristics and pre-planned descriptive analyses. Open question data were interpreted using thematic analysis. RESULTS: The response rate was 73.8%. Most surgeons (84%) were orthopaedic surgeons. Range of surgeon experience (1-15 years), number of operations performed in the previous 12 mo (4-250), and range of information used to predict outcome was broad. There was some consistency of practice: most patients were seen preoperatively; all surgeons ensured patients are mobile within 3 d of surgery; and there was agreement for the value of post-operative physiotherapy. However, there was considerable variability of practice: variability of protocols, duration of hospital stay, use of discharge criteria, frequency and timing of outpatient follow up, use of written patient information and outcome measures. Much variability was explained through patient-centred care, for example, 62% surgeons tailored functional advice to individual patients. CONCLUSION: Current United Kingdom surgeon practice for lumbar spinal fusion is described. The surgical procedure and patient population is diverse, and it is therefore understandable that management varies. It is evident that care should be patient-centred. However with high costs and documented patient dissatisfaction it is important that further research evaluates optimal management.

Genetic adaptation to levels of dietary selenium in recent human history.

As humans migrated around the world, they came to inhabit environments that differ widely in the soil levels of certain micronutrients, including selenium (Se). Coupled with cultural variation in dietary practices, these migrations have led to a wide range of Se intake levels in populations around the world. Both excess and deficiency of Se in the diet can have adverse health consequences in humans, with severe Se deficiency resulting in diseases of the bone and heart. Se is required by humans mainly due to its function in selenoproteins, which contain the amino acid selenocysteine as one of their constituent residues. To understand the evolution of the use of this micronutrient in humans, we surveyed the patterns of polymorphism in all selenoprotein genes and genes involved in their regulation in 50 human populations. We find that single nucleotide polymorphisms from populations in Asia, particularly in populations living in the extreme Se-deficient regions of China, have experienced concerted shifts in their allele frequencies. Such differentiation in allele frequencies across genes is not observed in other regions of the world and is not expected under neutral evolution, being better explained by the action of recent positive selection. Thus, recent changes in the use and regulation of Se may harbor the genetic adaptations that helped humans inhabit environments that do not provide adequate levels of Se in the diet.

Lessons learnt in the management of primary invasive penile cancer in an Australian tertiary referral centre: clinical outcomes with a minimum 48 months follow-up study.

PURPOSE: To report on lessons learnt in the management of primary invasive penile cancer in a major tertiary hospital in Australia. MATERIALS AND METHODS: Medical records for all patients who underwent surgery for primary invasive penile cancer between January 2000 and January 2011 were obtained. Patient demographics, clinical status of inguinal node, cancer stage and clinical outcomes were reviewed. All patients were followed up for a minimum of 48 months postoperative unless patient deceased within the first 48 months from the time of penile cancer surgery. RESULTS: Over the 11-year period, a total of 23 cases of invasive penile cancer were identified. Partial penectomy was the most common form of organ preserving surgery and the majority of patients have pT1b disease. Of the 9 patients with clinically palpable inguinal nodes, 7 patients were diagnosed with pN3 disease following inguinal lymphadenectomy. The Kaplan-Meier cancer-specific survival at 72 months showed decreasing survival based on tumour stage (83% in pT1, 79% in pT2, and 64% in pT3 disease) and nodal disease (100% in node negative, 50% in superficial inguinal lymphadenopathy, and 38% in patients with deep inguinal and/or pelvic lymphadenopathy) (p=0.082). The Kaplan-Meier cancer-specific survival revealed statistically significant difference in survival outcome in patients with local recurrence vs. systemic metastasis disease (33% vs. 17%, p=0.008). CONCLUSIONS: The presence of high risk features such as tumour stage, lymph node involvement and distant metastasis carries a significant higher risk of death and tumour recurrence in patients with penile cancer and inguinal lymph node metastasis.

Patterns of coding variation in the complete exomes of three Neandertals.

We present the DNA sequence of 17,367 protein-coding genes in two Neandertals from Spain and Croatia and analyze them together with the genome sequence recently determined from a Neandertal from southern Siberia. Comparisons with present-day humans from Africa, Europe, and Asia reveal that genetic diversity among Neandertals was remarkably low, and that they carried a higher proportion of amino acid-changing (nonsynonymous) alleles inferred to alter protein structure or function than present-day humans. Thus, Neandertals across Eurasia had a smaller long-term effective population than present-day humans. We also identify amino acid substitutions in Neandertals and present-day humans that may underlie phenotypic differences between the two groups. We find that genes involved in skeletal morphology have changed more in the lineage leading to Neandertals than in the ancestral lineage common to archaic and modern humans, whereas genes involved in behavior and pigmentation have changed more on the modern human lineage.

Developing a moderate sedation policy: essential elements and evidence-based considerations.

Developing an institutional policy for moderate sedation is a multidisciplinary effort that should involve close collaboration among clinicians, administrators, and risk managers. A variety of health care providers administer moderate sedation. Sedation policy should address essential elements, such as clinician training and credentialing, equipment, preprocedure evaluation, periprocedure patient monitoring, postprocedure observation and discharge, pharmaceutical agents, and outcomes assessment. Sedation policy should comply with local, state, and national guidelines and standards. Furthermore, sedation policy should be evidence based to incorporate the latest information about best practices and outcomes. Advances in pharmacology, monitoring, medication delivery systems, and simulation training can help improve quality of care and patient safety in the administration of moderate sedation.

SelenoDB 2.0: annotation of selenoprotein genes in animals and their genetic diversity in humans.

SelenoDB (http://www.selenodb.org) aims to provide high-quality annotations of selenoprotein genes, proteins and SECIS elements. Selenoproteins are proteins that contain the amino acid selenocysteine (Sec) and the first release of the database included annotations for eight species. Since the release of SelenoDB 1.0 many new animal genomes have been sequenced. The annotations of selenoproteins in new genomes usually contain many errors in major databases. For this reason, we have now fully annotated selenoprotein genes in 58 animal genomes. We provide manually curated annotations for human selenoproteins, whereas we use an automatic annotation pipeline to annotate selenoprotein genes in other animal genomes. In addition, we annotate the homologous genes containing cysteine (Cys) instead of Sec. Finally, we have surveyed genetic variation in the annotated genes in humans. We use exon capture and resequencing approaches to identify single-nucleotide polymorphisms in more than 50 human populations around the world. We thus present a detailed view of the genetic divergence of Sec- and Cys-containing genes in animals and their diversity in humans. The addition of these datasets into the second release of the database provides a valuable resource for addressing medical and evolutionary questions in selenium biology.

Structure and reactivity of bicyclic methylene aziridines prepared by intramolecular aziridination of allenes.

Unprecedented bicyclic methylene aziridines are prepared by rhodium(II)-catalyzed allene aziridination of buta-2,3-dienyl carbamates. Aspects of their NMR and X-ray data are described and a preliminary reactivity profile is given, including overall S(N)V-mode ring-opening with organometallic reagents.

A survey of post-operative management for patients following first time lumbar discectomy.

This study aimed to identify current NHS physiotherapy practice following first time lumbar discectomy in the United Kingdom (UK) in order to inform future research priorities and design. Descriptive survey methodology was utilised employing a postal questionnaire. A total population sample was identified and questionnaires were posted to 87 NHS physiotherapy departments throughout the UK. Participants were senior physiotherapists working with spinal surgery patients. In the inpatient phase, the majority of patients receive physiotherapy. Management focused on mobility and education to facilitate early discharge with most patients being given exercises. However, there was a wide variation in the actual exercises prescribed. There was more variation in the provision of outpatient physiotherapy treatment. Not all patients have access to physiotherapy treatment post discharge in the UK and when treatment was available the content and amount was variable. There is evidence to support rehabilitation classes to assist early improvements in function and return to work but such classes are only available in around half of the centres involved in this study. Regarding the content of exercise classes and individual treatment sessions, a wide range of clinical practice was evident. This study raises many research questions and highlights the need for future research to optimise patient rehabilitation following first time lumbar discectomy.

Ambient air concentrations of pesticides used in potato cultivation in Prince Edward Island, Canada.

Ambient air concentrations of nine selected pesticides used in potato cultivation were investigated on Prince Edward Island by collecting samples during the summer of 1998 at three potato farm sites and one non-agricultural site. In 1999, air samples were collected at a single potato farm site during local application of pesticides. The fungicide chlorothalonil was the only pesticide detected in every sample in both years, even in samples with a duration as little as 5 h. In 1998, maximum (45-458 ng m(-3)) and mean (22-193 ng m(-3)) concentrations of chlorothalonil from composite 42 h samples were one to two orders of magnitude greater at agricultural sites than at the non-agricultural site (3.9 and 2.5 ng m(-3), respectively). Maximum and mean concentrations of chlorothalonil from combined 24 h samples at the farm site in 1999 were higher than those measured in 1998 (636 and 284 ng m(-3), respectively). The ubiquitous presence in air of relatively high concentrations of chlorothalonil in agricultural areas on Prince Edward Island is likely related to its repeated use on potato farms where fungicides account for 80-90% of pesticides applied. Eight of nine pesticides were detected at farm sites in 1998 and they are ranked by mean concentration from highest to lowest as follows: chlorothalonil, methamidophos, azinphos-methyl, alpha-endosulfan, beta-endosulfan, pirimicarb, metobromuron, metribuzin, metalaxyl and fluazifop-P-butyl. Concentrations of metalaxyl, pirimicarb, metobromuron and fluazifop-P-butyl in air are among the first reported values for these pesticides. Five pesticides were detected at the Summerside farm in 1999, but only two fungicides (chlorothalonil and metalaxyl) were used locally, while the presence of metribuzin, alpha-endosulfan and methamidophos in air was not associated with local application. Evidence of pesticide drift was observed for chlorothalonil, alpha-endosulfan and methamidophos, and these pesticides were identified as being of high concern in terms of potential wildlife exposure on the Island.

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease.

BACKGROUND & AIMS: Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. METHODS: In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. RESULTS: Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. CONCLUSIONS: Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Using compensations to assess physical performance for ambulatory outpatients.

OBJECTIVE: To construct a physical performance scale for community-dwelling ambulatory outpatients that is linear, includes high functioning tasks, and uses common compensations to assess difficulty levels. DESIGN: Calibrated subject performances on 19 tasks were rated by an examiner, timed, and had compensations recorded. SETTING: Ambulatory outpatient physical therapy (PT) department of a tertiary care center. PARTICIPANTS: Convenience sample of 50 community-dwelling patients with difficulties in mobility referred for PT. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Community Ambulatory Physical Performance Scale (CAPPS) constructed by using Rasch analysis, the Lower Extremity Functional Scale (LEFS), and the six-minute walk test (6MWT). RESULTS: The CAPPS showed construct validity after removal of 3 items. Two additional items were removed for improved clinical utility. The person reliability was .89 and item reliability was .98. Subjects' performance on the CAPPS correlated with the 6MWT (r=.79; 95% confidence interval [CI], .65-.87) and with the LEFS (r=.62; 95% CI, .40-.78). CONCLUSIONS: The CAPPS showed good psychometric properties and has utility for assessments of higher-level physical functioning. This standardized approach to performance testing for ambulatory outpatients appears to be a promising method for articulating the compensations persons use to accomplish common tasks. Use of compensatory strategies to assess difficulties in physical performance may assist in delineating interventions directed toward improving task performance.

Factors affecting the duration effect in pitch perception for unresolved complex tones.

Previous research has shown that fundamental frequency (F0) discrimination thresholds for complex tones containing unresolved harmonics decrease as the duration of the tone increases [White and Plack, J. Acoust. Soc. Am. 103, 2051-2063 (1998)]. In this paper F0 discrimination was measured as a function of duration for complexes with F0s of 62.5, 125, and 250 Hz, bandpass filtered into two spectral regions (2750-3750 and 5500-7500 Hz). The harmonics were summed either in sine phase (SINE) or with alternating sine-cosine phase (ALT), which affects the envelope of the waveform and the pitch of the complex. Tone duration was 20, 40, 80, and 160 ms. The improvement in F0 discrimination with duration increased with decreasing F0. When harmonics where spectrally filtered between 2750 and 3750 Hz, for complexes with an F0 of 62.5 Hz, F0 discrimination thresholds decreased from approximately 30% for a 20-ms tone to approximately 3% for a 160-ms tone. For complexes with an F0 of 250 Hz, thresholds decreased from 3% for a 20-ms tone to 1% for a 160-ms tone: a lower envelope repetition rate led to a larger change in performance with increasing duration. The phase manipulation also affected the size of the duration effect, in that the effect was less for an ALT complex compared to a SINE complex with the same F0, consistent with the change in envelope repetition rate. Overall, the results suggest that for unresolved complex tones it is primarily envelope repetition rate, not spectral region, that determines both the F0 discrimination threshold and the size of the duration effect.