High prevalence of radiographic outliers and revisions with unicompartmental knee arthroplasty

BACKGROUND: Alignment outcomes and their impact on implant survival following unicompartmental knee arthroplasty (UKA) are unclear. The purpose of this study was to assess the implant survival and radiographic outcomes after UKA as well as the impact of component alignment and overhang on implant survival. METHODS: We performed a retrospective analysis of 253 primary fixed-bearing and mobile-bearing medial UKAs from a single academic center. All UKAs were performed by 2 high-volume fellowship-trained arthroplasty surgeons. UKAs comprised \u3c10% of their knee arthroplasty practices, with an average of 14.2 medial UKAs per surgeon per year. Implant survival was assessed. Femoral coronal (FCA), femoral sagittal (FSA), tibial coronal (TCA), and tibial sagittal (TSA) angles as well as implant overhang were radiographically measured. Outliers were defined for FCA (\u3e±10° deviation from neutral), FSA (\u3e15° of flexion), TCA (\u3e±5° deviation from neutral), and TSA (\u3e±5° deviation from 7°). Far outliers were an additional \u3e±2° of deviation. Outliers for overhang were identified as \u3e3 mm for anterior overhang, \u3e2 mm for posterior overhang, and \u3e2 mm for medial overhang. RESULTS: Among patients with a failed UKA, revision was performed at an average of 3.7 years (range, 0.03 to 8.7 years). The cumulative revision rate was 14.2%. Kaplan-Meier survival analysis demonstrated 5 and 10-year survival rates of 88.0% (95% confidence interval [CI] = 82.0% to 91.0%) and 70.0% (95% CI = 56.0% to 80.0%), respectively. Only 19.0% (48) of the UKAs met target alignment for all 4 alignment measures, and only 72.7% (184) met all 3 targets for overhang. Only 11.9% (30) fell within all alignment and overhang targets. The risk of implant failure was significantly impacted by outliers for FCA (failure rate = 15.4%, p = 0.036), FSA (16.2%, p = 0.028), TCA (17.9%, p = 0.020), and TSA (15.2%, p = 0.034) compared with implants with no alignment or overhang errors (0%); this was also true for far outliers (p \u3c 0.05). Other risk factors for failure were posterior overhang (failure rate = 25.0%, p = 0.006) and medial overhang (38.2%, p \u3c 0.001); anterior overhang was not a significant risk factor (10.0%, p = 0.090). CONCLUSIONS: The proportions of UKA revisions and alignment outliers were greater than expected, even among high-volume arthroplasty surgeons performing an average of 14.2 UKAs per year (just below the high-volume UKA threshold of 15). Alignment and overhang outliers were significant risk factors for implant failure. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

The impact of surgeon volume and training status on implant alignment in total knee arthroplasty

BACKGROUND: Implant malalignment may predispose patients to prosthetic failure following total knee arthroplasty (TKA). A more thorough understanding of the surgeon-specific factors that contribute to implant malalignment following TKA may uncover actionable strategies for improving implant survival. The purpose of this study was to determine the impact of surgeon volume and training status on malalignment. METHODS: In this retrospective multicenter study, we performed a radiographic analysis of 1,570 primary TKAs performed at 4 private academic and state-funded centers in the U.S. and U.K. Surgeons were categorized as high-volume (≥50 TKAs/year) or low-volume (\u3c50 TKAs/year), and as a trainee (fellow/resident under the supervision of an attending surgeon) or a non-trainee (attending surgeon). On the basis of these designations, 3 groups were defined: high-volume non-trainee, low-volume non-trainee, and trainee. The postoperative medial distal femoral angle (DFA), medial proximal tibial angle (PTA), and posterior tibial slope angle (PSA) were radiographically measured. Outlier measurements were defined as follows: DFA, outside of 5° ± 3° of valgus; PTA, \u3e±3° deviation from the neutral axis; and PSA, \u3c0° or \u3e7° of flexion for cruciate-retaining or \u3c0° or \u3e5° of flexion for posterior-stabilized TKAs. Far outliers were defined as measurements falling \u3e± 2° outside of these ranges. The proportions of outliers were compared between the groups using univariate and multivariate analyses. RESULTS: When comparing the high and low-volume non-trainee groups using univariate analysis, the proportions of knees with outlier measurements for the PTA (5.3% versus 17.4%) and PSA (17.4% versus 28.3%) and the proportion of total outliers (11.8% versus 20.7%) were significantly lower in the high-volume group (all p \u3c 0.001). The proportions of DFA (1.9% versus 6.5%), PTA (1.8% versus 5.7%), PSA (5.5% versus 12.6%), and total far outliers (3.1% versus 8.3%) were also significantly lower in the high-volume non-trainee group (all p \u3c 0.001). Compared with the trainee group, the high-volume non-trainee group had significantly lower proportions of DFA (12.6% versus 21.6%), PTA (5.3% versus 12.0%), PSA (17.4% versus 33.3%), and total outliers (11.8% versus 22.3%) (all p \u3c 0.001) as well as DFA (1.9% versus 3.9%; p = 0.027), PSA (5.5% versus 12.6%; p \u3c 0.001), and total far outliers (3.1% versus 6.4%; p = 0.004). No significant differences were identified when comparing the low-volume non-trainee group and the trainee group, with the exception of PTA outliers (17.4% versus 12.0%; p = 0.041) and PTA far outliers (5.7% versus 2.6%; p = 0.033). Findings from multivariate analysis accounting for the effects of patient age, body mass index, and individual surgeon demonstrated similar results. CONCLUSIONS: Low surgical volume and trainee status were risk factors for outlier and far-outlier malalignment in primary TKA, even when accounting for differences in individual surgeon and patient characteristics. Trainee surgeons performed similarly, and certainly not inferiorly, to low-volume non-trainee surgeons. Even among high-volume non-trainees, the best-performing cohort in our study, the proportion of TKA alignment outliers was still high. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence

AMP: a new time-frequency feature extraction method for intermittent time-series data

The characterisation of time-series data via their most salient features is extremely important in a range of machine learning task, not least of all with regards to classification and clustering. While there exist many feature extraction techniques suitable for non-intermittent time-series data, these approaches are not always appropriate for intermittent time-series data, where intermittency is characterized by constant values for large periods of time punctuated by sharp and transient increases or decreases in value. Motivated by this, we present aggregation, mode decomposition and projection (AMP) a feature extraction technique particularly suited to intermittent time-series data which contain time-frequency patterns. For our method all individual time-series within a set are combined to form a non-intermittent aggregate. This is decomposed into a set of components which represent the intrinsic time-frequency signals within the data set. Individual time-series can then be _t to these components to obtain a set of numerical features that represent their intrinsic time-frequency patterns. To demonstrate the effectiveness of AMP, we evaluate against the real word task of clustering intermittent time-series data. Using synthetically generated data we show that a clustering approach which uses the features derived from AMP significantly outperforms traditional clustering methods. Our technique is further exemplified on a real world data set where AMP can be used to discover groupings of individuals which correspond to real world sub-populations

Class III β-tubulin expression as a predictor of docetaxel-resistance in metastatic castration-resistant prostate cancer

About half of the patients treated with docetaxel in the setting of metastatic castration-resistant prostate cancer (CRPC) are non-responders. Therefore, a marker of response would be beneficial for clinical decision-making. We evaluated class III β-tubulin (βIII-tubulin) expression as a predictor of resistance in this setting, which previously has been correlated with lack of response to taxanes in other cancers. Patients with CRPC were included if they were treated with at least 3 cycles of docetaxel between 1990 and 2011. βIII-tubulin expression was assessed by immunostaining, which was performed in tissue samples obtained either via biopsy or prostatectomy at the time of diagnosis. Rates of prostate-specific antigen (PSA) response and overall survival (OS) following docetaxel treatment were compared between patients with high (2+ or 3+ staining) vs. low (0 or 1+ staining) βIII-tubulin expression. Of 73 patients, 26 (35%) had a high expression of βIII-tubulin. A PSA decline of 10% or greater occurred in 65% of patients with a high βIII-tubulin expression vs. 89% with a low βIII-tubulin expression (p = 0.0267). The median OS for patients with a high βIII-tubulin expression was 17.4 (95% CI 8.7-21.0) months vs. 19.8 (95% CI 16.6-23.6) months for patients with a low expression (p = 0.039). Our results show that a high βIII-tubulin expression is a negative prognostic factor in metastatic CRPC patients treated with docetaxel

Serum Dioxin, Testosterone, and Subsequent Risk of Benign Prostatic Hyperplasia: A Prospective Cohort Study of Air Force Veterans

BACKGROUND: Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange, during the Vietnam War in 1962–1971; Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias. OBJECTIVES: In this study, our objective was to assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels. METHODS: This study was a longitudinal, prospective cohort study made up of U.S. Air Force veterans involved in Operation Ranch Hand. Other Air Force veterans who did not spray herbicides were included as comparisons. BPH was determined by medical record review and by medical examinations conducted during the study. Data were available for 971 Ranch Hand and 1,266 comparison veterans. We investigated the relationship between BPH and serum TCDD level using the Cox proportional hazards models adjusted for testosterone levels, body mass index (BMI), and the percentage change in BMI per year. RESULTS: In univariate and multivariate analyses, the risk of BPH decreased with increasing serum TCDD in the comparison group. The multivariate risk ratio for BPH in the comparison group was 0.84 (95% confidence interval, 0.73–0.98). Excluding men with prostate cancer, inflammatory or other prostatic diseases did not substantially alter the association. Serum testosterone levels were inversely associated with serum TCDD levels in both Ranch Hand and comparison groups. CONCLUSIONS: TCDD exposure at general population levels is associated with a decreasing risk of BPH with higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels

Modelling cell cycle synchronisation in networks of coupled radial glial cells

Radial glial cells play a crucial role in the embryonic mammalian brain. Their proliferation is thought to be controlled, in part, by ATP mediated calcium signals. It has been hypothesised that these signals act to locally synchronise cell cycles, so that clusters of cells proliferate together, shedding daughter cells in uniform sheets. In this paper we investigate this cell cycle synchronisation by taking an ordinary differential equation model that couples the dynamics of intracellular calcium and the cell cycle and extend it to populations of cells coupled via extracellular ATP signals. Through bifurcation analysis we show that although ATP mediated calcium release can lead to cell cycle synchronisation, a number of other asynchronous oscillatory solutions including torus solutions dominate the parameter space and cell cycle synchronisation is far from guaranteed. Despite this, numerical results indicate that the transient and not the asymptotic behaviour of the system is important in accounting for cell cycle synchronisation. In particular, quiescent cells can be entrained on to the cell cycle via ATP mediated calcium signals initiated by a driving cell and crucially will cycle in near synchrony with the driving cell for the duration of neurogenesis. This behaviour is highly sensitive to the timing of ATP release, with release at the G1/S phase transition of the cell cycle far more likely to lead to near synchrony than release during mid G1 phase. This result, which suggests that ATP release timing is critical to radial glia cell cycle synchronisation may help to understand normal and pathological brain development

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

Leadership Styles

[First paragraph] Effective schools literature shows clearly that the leadership of the principal is key to the effectiveness of the school (Hoy and Miskell, 1982, and Arnn and Mangieri, 1988). To be effective, principals must use leadership styles appropriate to the situation