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Biceps-labrum complex (BLC) disease is a well-established pain generator in the shoulder. Despite its ubiquity, BLC disease continues to pose a diagnostic challenge for orthopaedic surgeons. The use of magnetic resonance imaging and glenohumeral arthroscopy in the diagnosis of BLC disease has proven to be inadequate when performed independently. As a result, physical examination remains a critical component in the evaluation of BLC disease. The purpose is to provide a comprehensive compendium of physical examination maneuvers in the evaluation of BLC disease.

Objective: To evaluate the efficacy and safety of 2 doses of vilaprisan vs. placebo in participants with symptomatic endometriosis. Design: Multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2b trial (NCT03573336). The initially planned sample size was 315 patients. Recruitment was paused to assess long-term toxicity findings in rodents; although the findings were assessed as likely to be of limited clinical relevance in humans, the study was closed by the sponsor. During the pause, enrolled patients completed 3 or 6 months of treatment per their assigned regimen. Setting: University hospitals, a regional hospital, and a private clinic. Patients: Premenopausal adults with confirmed endometriosis and moderate-to-severe pelvic pain (≥4/10 on a numerical rating scale) were enrolled. Inclusion required protocol adherence, including ≥24 diary entries, and an average pain score of ≥3.5. Intervention: Participants were randomly assigned 1:1:1 to receive vilaprisan (2 mg), vilaprisan (4 mg), or placebo. Main Outcome Measures: The primary outcome was a change in the 7-day mean “worst pain” (per the endometriosis symptom diary item 1) from baseline to month 3. All analyses were descriptive only. Results: Eight participants were randomly assigned to treatment before the study pause: 6 received vilaprisan (4 mg, n = 4 and 2 mg, n = 2), and 2 received placebo. The 6 vilaprisan recipients experienced an improvement in endometriosis-associated pelvic pain, whereas the 2 placebo recipients experienced no change or increased pain; all 8 participants had decreased use of pain medication. Bleeding intensity decreased from baseline in the vilaprisan group. Conclusion: The study findings suggest that vilaprisan may improve outcomes in patients with endometriosis. Further studies in larger populations would be needed to accurately assess treatment effects. Clinical Trial Registration Number: NCT03573336

Private equity investment in fertility clinics has rapidly increased and is leading to unprecedented changes in the field of reproductive endocrinology and infertility (REI). The goal of this paper was to review private equity’s current integration in REI and discuss both benefits and challenges of investor involvement. We found that at least 25% of fellowship programs and medical schools were affiliated with private practice fertility clinics, not free-standing academic clinics. Approximately half of medical schools and nearly all REI fellowship programs that were affiliated with private practices were also backed by private investors. Research participation remains robust in private equity-affiliated REI clinics. With the changing infrastructure, we discuss the potential influence on trainee experience and research while also acknowledging the unique advantages that investor involvement may offer.

Gonadotropin-releasing hormone (GnRH) is central to the control of the entire hypothalamic-pituitary-gonadal axis. Manipulation of GnRH, in turn, regulates pituitary response and ovarian hormone production. Gonadotropin-releasing hormone analogues have revolutionized assisted reproductive technology and gynecologic practice. The recent advent of oral GnRH antagonists with an inherent rapid onset of action continues to transform the treatment options available for several common gynecologic conditions, including endometriosis and fibroids. Herein, we review neuroendocrine GnRH activity and discuss modulation of the reproductive axis by GnRH analogues for diverse clinical applications.

Surgical intervention is often recommended for refractory pathology affecting the biceps-labrum complex. Tenodesis of the long head of the biceps tendon (LHBT) is a widely accepted treatment modality; however, the optimal technique remains elusive. Arthroscopic subdeltoid transfer of the LHBT to the conjoint tendon, as described in this technical note, continues to demonstrate excellent clinical results. Its advantages include soft tissue–to–soft tissue healing, an advantageous biomechanical construct, and comprehensive evaluation and decompression of the LHBT including the extra-articular bicipital tunnel. The primary limitation of this procedure is the perceived learning curve for safe navigation within the subdeltoid space.

Objective: To examine and further characterize the association between urinary levels of triclosan (TCS), a ubiquitous putative endocrine-disrupting chemical, and the risk of infertility. Design: A retrospective cross-sectional study using the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey. Setting: Not applicable. Patient(s): Female participants in the United States who completed the reproductive health questionnaire and provided urine samples for TCS level measurement from 2013 to 2016. Intervention(s): None. Main Outcome Measure(s): Rates of presumed infertility based on participants’ affirmative response to survey question RHQ074 (“Have you ever attempted to become pregnant over a period of at least a year without becoming pregnant?”). Result(s): A total of 11.7% of the overall female and 12.5% of the eligible study population met the criterion for presumed infertility. Creatinine-adjusted urinary TCS levels were significantly higher among those meeting the criterion for infertility compared with the levels among those who did not. On multivariable-adjusted analyses, individuals with undetectable levels of urinary TCS were 35% less likely to meet the specified infertility criterion compared with those with detectable TCS levels. The magnitude of association between TCS levels and infertility was strongest when comparing the lowest and highest quartiles. The directionality and magnitude of the relationship between TCS levels and infertility were maintained on age-restricted and weighted analyses; however, the associations did not retain statistical significance. Conclusion(s): In a nationally representative sample of women in the United States, an association between TCS exposure and inability to conceive over a period of 1 year is suggested by our analysis of the National Health and Nutrition Examination Survey data. The data infer a dose-response relationship.

Objective: To study the association between high-sensitivity C-reactive protein (hs-CRP) and infertility among reproductive-age women while controlling for obesity and other metabolic markers. Previous studies found a link between infertility and cardiovascular diseases (CVDs). C-reactive protein is a sensitive marker of CVDs, and its levels are affected by obesity. Design/Setting: We conducted a cross-sectional study using national data from 2015 through 2018. Patients: A total of 940 women aged 20–45 years who self-reported infertility, had hs-CRP values measured, and did not have CRP >10 mg/L, asthma, arthritis, bronchitis, thyroid disease, bilateral oophorectomy, hysterectomy, and who were not breastfeeding or pregnant, premenarchal at the time of study or had menarche after the age of 20. Interventions: N/A. Main outcome measure(s): Infertility status (ever reporting inability to conceive with 12 months of trying to become pregnant). Results: In comparison to noninfertile women, self-reported infertile women had higher mean of hs-CRP (3.11 mg/L vs. 2.40 mg/L) and higher percentage of moderate/high hs-CRP values (77.0% vs 58.8%). However, after adjusting for metabolic markers, there was a nonsignificant association between moderate/high hs-CRP and self-reported infertility in the multivariable logistic regression analysis. Odds ratio estimates of the association between hs-CRP and infertility increased over 40% after removing obesity measures and/or high-density lipoprotein from regression models. Conclusion: There was no association between hs-CRP and self-reported infertility after controlling for obesity measures and other risk factors for CVDs in a sample of U.S. women aged 20–45 years.

The athlete with shoulder instability poses a unique challenge to the sports medicine team. Clinical studies support surgical intervention followed by a phased approach to rehabilitation. In the latter phases, it is important to tailor this program to the individual’s specific athletic needs, which requires ongoing qualitative assessment and objective measurement. Passing a return-to-sport testing battery has been shown to decrease the risk of recurrent instability. What is lacking in the literature is a consensus for how to best measure shoulder performance when the required athletic demands are widely varied by hand dominance, sport played, and playing position. Multiple upper-extremity tests have been described in the literature, but there is no consensus on which tests should be used to direct rehabilitation and to safely return the athlete to unrestricted athletic exposure. Using available evidence, we suggest a framework for return-to-play testing that integrates traditional rehabilitation phases with performance testing and graduated sports exposure. Level of Evidence: Level V, expert opinion.

Rotator cuff tears are increasing in frequency in the aging population and are a common issue seen by orthopaedic surgeons. In patients with large, multi-tendon rotator cuff tears or retears, treatment can be challenging. Failure rates of up to 90% have been reported for rotator cuff repair (RCR) of large, multi-tendon tears. Biological augmentation has been an area of interest because of the distinctly different biology of the repaired tendon compared with the native tendon. These biological differences affect the ultimate tensile properties of the repair and may contribute to gap formation and the high failure rate of repairs. RCR with allograft augmentation is a technique that shows potential benefit to healing and preventing retears. Arthroscopic augmentation of RCRs can be challenging. The technique described in this Technical Note illustrates a simple and easily reproducible method for augmenting RCRs with human acellular dermal allograft.

Biceps tenodesis is a commonly employed surgical intervention for refractory symptoms related to the biceps-labral complex, those intra-articular and those within the extra-articular bicipital tunnel. While a litany of surgical techniques exists, the optimal method for ensuring an anatomic length-tension relationship during tenodesis remains elusive. Appropriate tensioning may limit undesirable outcomes such as cramping or cosmetic deformity. We describe herein our technique as a simple and efficient means to establish patient-specific, anatomic tensioning of the long head of the biceps during tenodesis.

The active compression test (O'Brien Sign) is widely used by physicians to aid in the diagnosis of biceps-labrum complex disease. This maneuver has been particularly criticized in the literature, however, with regard to interobserver reliability. Criticisms may in fact stem from inaccurate and inconsistent practice of the examination maneuver, stemming from both patient- and physician-related errors. In this Technical Note, we introduce an easy modification to the O'Brien Sign that limits such errors and improves test uniformity.

Posterior cruciate ligament (PCL) reconstruction using the transtibial drilling or arthroscopic tibial-inlay technique has a risk of injury to the popliteal neurovascular bundle because a pin is drilled anterior to posterior. Intraoperative fluoroscopy is used to decrease the risk of neurovascular injury. In addition, graft passage in the transtibial technique may be problematic because of a sharp turn when placing the graft into the tibial tunnel, which may damage graft fibers. In the surgical technique described in this report, the posteromedial portal is used for visualization and the posterolateral portal is used for debridement of the PCL tibial footprint and the synovial fold closest to the PCL. A curved guide is placed from the posterolateral portal to the tibial footprint, and a flexible pin is drilled across the tibia. The tibial tunnel is then created using a flexible reamer under direct visualization up to the desired length, and a graft can be positioned in the tibial tunnel through the posterolateral portal. This technique has the potential advantages of decreasing the risk of injury to the popliteal neurovascular bundle (use of anteriorly directed, inside-out drilling), avoiding a sharp turn during graft passage, and allowing accurate and anatomic tibial tunnel placement without intraoperative fluoroscopy.

This paper assesses a potentially interesting soil process, dealumination, as the mechanism for the increase observed in strong acid recoverable Al and associated elements in farmed soils compared with background soils in the Waikato Region of New Zealand. Waikato Regional Council has been measuring an established set of 7 soil quality chemical and physical parameters and concentrations of 33 elements as part of a Regional Soil Quality Monitoring program since 2003. Statistical comparison of farmed to background soils, relative surface enrichments, and inter-element correlations enable us to infer likely and potential sources of those elements which show some form of enrichment. Acid-recoverable Al is 1.5 times higher (P < 0.0001) in the Waikato region's farmed soils than its background soils. This increase is not readily explained as an external source of recoverable Al (due to lack of enrichment at the soil surface). However, it could be explained as an increase in the concentration of acid-recoverable Al as a result of accelerated weathering or chemical attack of primary crystalline and short-range order aluminosilicates. In keeping with this interpretation, acid recoverable concentrations of several trace elements that are normally retained inside aluminosilicates (in residual phases) are also significantly higher in farmed than background soils but are not selectively enriched at the soil surface. These include (with enrichment-to-background factors) Li (2.5), La (2.1), Mn (1.5), and Ag, Bi, Mo, Sn, and TI (1.4). Also, this process may contribute one-quarter of the observed increase in acidrecoverable U. If it is occurring, accelerated Al weathering may be a normal part of an increase in soil productivity, or may be facilitated by an external agent capable of attacking crystalline aluminosilicates. A candidate in the latter category is the F (and/or possibly free HF) in phosphate fertilisers, because this substantially increases Al species in soil porewater. Two specific mechanisms that could favour Al mobilisation from clay surfaces include partial dissolution by local areas of high acidity associated with fertiliser granules, and surface complexation and extraction by the fluoride and residual hydrofluoric acid present in phosphate fertilisers. Based on the high reactivity between F and both Al and Si, potential exists for significant production of SiF4(g) as another side-effect of phosphate fertiliser use. Additional keywords: dealumination, clay mineral alterations, soil quality, monitoring, phosphate analogues, chromate, silicon tetra fluoride., Introduction The Waikato Region (Fig. 1) covers much of the Central North Island of New Zealand, extending south of Lake Taupo and Turangi to the Bombay Hills, and with a [...]

Abstract. The objective of this study was to characterize the transfer of flecainide across the placenta and determine the fetal: maternal ratio of flecainide in the gravid baboon. Flecainide acetate [...]

Sewage sludge is increasingly been applied to land in New Zealand in an attempt to recycle the valuable plant nutrients such material contains. However, there are concerns regarding the environmental fate of heavy metals contained in the sludge. This study examines the soil profile distributions of metals (Cd, Cr, Cu, Ni, Pb, Zn) in large undisturbed soil lysimeters treated with metal-spiked sewage sludge, following 3 years of drainage leachate monitoring. For 3 forest soils that had all received surface applications of sludge, analytical results demonstrated considerable transport of metals from the sludge into the underlying litter and mineral soil layers. Determination of individual metal/Cr ratios revealed considerable differential mobility between metals, with Cd, Ni, and Zn being most mobile, and Cu and Pb being only slightly more mobile than Cr. Total metal analysis was relatively insensitive in detecting metal movement down the soil profile compared with determination of extractable metals (EDTA or [Ca(N[O.sub.3]).sub.2] extraction). Maximum depths of metal penetration varied between metals, but were similar for all 3 forest soils, averaging 0.15, 0.20, 0.25, 0.35, and 0.45 m for Pb, Cu, Cd, Ni, and Zn, respectively. In contrast to the forest soils, when sludge was incorporated into the top 0.10 m of 2 pasture soils, little movement of metals could be detected below the layer of incorporation. However, even in these soils, the determination of metal/Cr ratios indicated that some differential movement of metals had taken place. For the forest soils, the results indicate considerable potential for the long-term and sustained leaching of metals by normal convective and diffusive transport processes. This would appear to be of less concern where sludge has been incorporated into the pasture soils. These results clearly have implications for selection of the most appropriate soils and conditions for sludge application to the land. Additional keywords: cadmium, chromium, copper, lead, nickel, zinc., Introduction In New Zealand, protection of groundwater is a major issue, and the increasing pressure for land treatment of sewage sludge has raised the question of potential nutrient and metal [...]

This study investigated the influence of childhood IQ on the relationships between risk factors and cardiovascular disease (CVD), coronary heart disease (CHD) and stroke in adulthood. Participants were from the Midspan prospective cohort studies which were conducted on adults in Scotland in the 1970s. Data on risk factors were collected from a questionnaire and at a screening examination, and participants were followed up for 25 years for hospital admissions and mortality. 938 Midspan participants were successfully matched with their age 11 IQ from the Scottish Mental Survey 1932, in which 1921-born children attending schools in Scotland took a cognitive ability test. Childhood IQ was negatively correlated with diastolic and systolic blood pressure, and positively correlated with height and respiratory function in adulthood. For each of CVD, CHD and stroke, defined as either a hospital admission or death, there was an increased relative rate per standard deviation decrease (15 points) in childhood IQ of 1.11 (95% confidence interval 1.01-1.23), 1.16 (l.03-1.32) and 1.10 (0.88-1.36), respectively. With events divided into those first occurring before and those first occurring after the age of 65, the relationships between childhood IQ and CVD, CHD and stroke were only seen before age 65 and not after age 65. Blood pressure, height, respiratory function and smoking were associated with CVD events. Relationships were stronger in the early compared to the later period for smoking and FEV1, and stronger in the later compared to the earlier period for blood pressure. Adjustment for childhood IQ had small attenuating effects on the risk factor--CVD relationship before age 65 and no effects after age 65. Adjustment for risk factors attenuated the childhood IQ--CVD relationship by a small amount before age 65. Childhood IQ was associated with CVD risk factors and events and can be considered an important new risk factor. Keywords: Cardiovascular disease; Cohort; Mental ability; Mortality; Risk factors; Scotland

The extent of metal (Cd, Cr, Cu, Ni, Pb, Zn) leaching from soils treated with metal-spiked sewage sludge was examined using large undisturbed soil lysimeters of 5 different New Zealand soils (2 pasture and 3 forest soils). Metal leaching from the soils was monitored continuously over a period of 3 years following a single application of sewage sludge. Metal speciation in leachates was estimated using GEOCHEM-PC. Application of the sludge resulted in decreased pH and increased concentrations and total amounts of Cd, Ni, and Zn in drainage leachates from some of the soils, but had little effect on, or decreased concentrations of, Cr, Cu, and Pb. In the case of Cu, and to a lesser extent Pb, the reduced leaching of these metals in the forest soils was considered related to the lack of plant cover and reduced pH and soluble organic C in leachates from the sludge-treated lysimeters. The peaking of Ni and Zn concentrations well before 1 pore volume of water had passed through the lysimeters indicated that macropore flow was an important process facilitating the leaching of these metals. The extent of metal leaching varied greatly between soils and was dependent on a number of soil properties and other factors, including plant cover (pasture v. forest soils). However, even under the extreme conditions of the study, very small proportions (~1% or less) of the applied metals were leached over the 3-year period. In some cases, Ni and Zn concentrations in drainage leachates exceeded drinking water and/or environmental standards. However, with further attenuation and dilution in the vadose zone, in the short-term at least, the leaching of these metals would seem unlikely to pose a major environmental threat. Additional keywords: cadmium, chromium, copper, lead, nickel, zinc., Introduction It has been generally considered that the presence of metals in soil treated with sewage sludge is confined to the cultivation zone with very little movement below that depth [...]

This paper describes the redesign of the HP turbine of the Rolls-Royce Trent 500 engine, making use of nonaxisymmetric end walls. The original, datum turbine used conventional axisymmetric end walls, while the vane and (shrouded) rotor aerofoil profiles were nominally the same for the two designs. Previous research on the large-scale, low-speed linear cascade at Durham University (see Hartland et al. Compositor: complete ref. in Abstract), had already demonstrated significant potential for reducing turbine secondary losses using nonaxisymmetric end walls-by about one third. This paper shows how a methodology was derived from the results of this research and applied to the design of the single-stage Trent 500-HP turbine (model rig). In particular, the application of a new linear design system for the parametric definition of these end wall shapes (described in Harvey et al. Compositor: complete ref. in Abstract) is discussed in detail. [DOI: 10.1115/1.1450766]