An evidence-based radiographic Decision Aid for meniscal-bearing unicompartmental knee arthroplasty (UKA) has been developed and this study investigates its performance at an independent centre.
...Pre-operative radiographs, including stress views, from a consecutive cohort of 550 knees undergoing arthroplasty (UKA or total knee arthroplasty; TKA) by a single-surgeon were assessed. Suitability for UKA was determined using the Decision Aid, with the assessor blinded to treatment received, and compared with actual treatment received, which was determined by an experienced UKA surgeon based on history, examination, radiographic assessment including stress radiographs, and intra-operative assessment in line with the recommended indications as described in the literature.
The sensitivity and specificity of the Decision Aid was 92% and 88%, respectively. Excluding knees where a clear pre-operative plan was made to perform TKA, i.e. patient request, the sensitivity was 93% and specificity 96%. The false-positive rate was low (2.4%) with all affected patients readily identifiable during joint inspection at surgery. In patients meeting Decision Aid criteria and receiving UKA, the five-year survival was 99% (95% confidence intervals (CI) 97 to 100). The false negatives (3.5%), who received UKA but did not meet the criteria, had significantly worse functional outcomes (flexion p < 0.001, American Knee Society Score - Functional p < 0.001, University of California Los Angeles score p = 0.04), and lower implant survival of 93.1% (95% CI 77.6 to 100).
The radiographic Decision Aid safely and reliably identifies appropriate patients for meniscal-bearing UKA and achieves good results in this population. The widespread use of the Decision Aid should improve the results of UKA. Cite this article: Bone Joint J 2016;98-B(10 Suppl B):3-10.
Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development ...of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. In vivo, S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Moreover, MCL1 inhibition, either alone or in combination with other anti-cancer drugs, proved effective against several solid cancer-derived cell lines. These results point towards MCL1 as a target for the treatment of a wide range of tumours.
Autoantibodies may be present in a variety of underlying cancers several years before tumours can be detected and testing for their presence may allow earlier diagnosis. We report the clinical ...validation of an autoantibody panel in newly diagnosed patients with lung cancer (LC).
Three cohorts of patients with newly diagnosed LC were identified: group 1 (n = 145), group 2 (n = 241) and group 3 (n = 269). Patients were individually matched by gender, age and smoking history to a control individual with no history of malignant disease. Serum samples were obtained after diagnosis but before any anticancer treatment. Autoantibody levels were measured against a panel of six tumour-related antigens (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2). Assay sensitivity was tested in relation to demographic variables and cancer type/stage.
The autoantibody panel demonstrated a sensitivity/specificity of 36%/91%, 39%/89% and 37%/90% in groups 1, 2 and 3, respectively, with good reproducibility. There was no significant difference between different LC stages, indicating that the antigens included covered the different types of LC well.
This assay confirms the value of an autoantibody panel as a diagnostic tool and offers a potential system for monitoring patients at high risk of LC.
Photometry and performance of SPECULOOS-South Murray, C A; Delrez, L; Pedersen, P P ...
Monthly notices of the Royal Astronomical Society,
06/2020, Letnik:
495, Številka:
2
Journal Article, Web Resource
Recenzirano
Odprti dostop
ABSTRACT
SPECULOOS-South, an observatory composed of four independent 1-m robotic telescopes, located at ESO Paranal, Chile, started scientific operation in 2019 January. This Southern hemisphere ...facility operates as part of the Search for Habitable Planets EClipsing ULtra-cOOl Stars (SPECULOOS), an international network of 1-m-class telescopes surveying for transiting terrestrial planets around the nearest and brightest ultracool dwarfs (UCDs). To automatically and efficiently process the observations of SPECULOOS-South, and to deal with the specialized photometric requirements of UCD targets, we present our automatic pipeline. This pipeline includes an algorithm for automated differential photometry and an extensive correction technique for the effects of telluric water vapour, using ground measurements of the precipitable water vapour. Observing very red targets in the near-infrared can result in photometric systematics in the differential light curves, related to the temporally-varying, wavelength-dependent opacity of the Earth’s atmosphere. These systematics are sufficient to affect the daily quality of the light curves, the longer time-scale variability study of our targets and even mimic transit-like signals. Here we present the implementation and impact of our water vapour correction method. Using the 179 nights and 98 targets observed in the I + z′ filter by SPECULOOS-South since 2019 January, we show the impressive photometric performance of the facility (with a median precision of ∼1.5 mmag for 30-min binning of the raw, non-detrended light curves) and assess its detection potential. We compare simultaneous observations with SPECULOOS-South and TESS, to show that we readily achieve high-precision, space-level photometry for bright, UCDs, highlighting SPECULOOS-South as the first facility of its kind.
We report a review examining the psychological wellbeing of parents of children with Down syndrome (DS) relative to that of parents of typically developing (TD) children. A systematic search ...identified 57 relevant studies, which were synthesised meta-analytically. Relative to their counterparts with TD children, mothers and fathers of children with DS reported higher levels of parenting stress (mothers: g = 0.57, 95% CI 0.33, 0.81; fathers: g = 0.40, 0.24, 0.56), depressive symptoms (mothers: g = 0.42, 0.23, 0.61; fathers: g = 0.25, 0.02, 0.48) and psychological distress (mothers: g = 0.45, 0.30, 0.60; fathers: g = 0.63, 0.26, 0.99). Small effects were found for anxiety for mothers (g = 0.16, 0.03, 0.29), with no differences for fathers (g = 0.03, −0.25, 0.32). No group differences were found for positive impact of parenting (mothers: g = −0.09, −0.25, 0.07; fathers: g = −0.04, −0.30, 0.22), while evidence concerning other positive wellbeing outcomes was limited. No significant moderating effects of child age range, country income level, or group differences in parental education level were identified, but limited subgroup analyses were possible. Raising a child with DS may be associated with elevated stress, depressive symptoms, and psychological distress for mothers and fathers. However, levels of parenting reward appear equivalent to those experienced by parents raising TD children.
•We reviewed psychological wellbeing in parents of children with Down syndrome and typical development.•Parents of children with Down syndrome had elevated stress and depressive symptoms.•There were no group differences in positive impact of parenting.•Evidence concerning other positive wellbeing outcomes was limited.
In southern Africa, the Okavango Delta is a large alluvial fan sustaining a unique wetlands ecosystem in the heart of the Kalahari desert. The Delta is fed by an annual flood that brings water from ...the Angolan plateaus to the north, down to the Okavango region. The fan is characterized by vegetated, permanent or seasonal floodplains, dotted with thousands of sandy islands of various origin (inverted paleo‐channels, paleo‐dunes, meander bars, etc). On at least some of these islands, shallow groundwater is characterized by a high pH (>8) and a high concentration of metals and metalloids, making it naturally toxic. In the 1990s, McCarthy and co‐workers explain the chemistry of that water through an evapotranspiration model, the flood‐water being pumped by the vegetation toward the center of the islands and progressively enriched in elements by evapotranspiration. This model has been widely applied to all islands in the Okavango, not considering their individual specificities nor that of the surrounding floodplain. Our work, based on a multidisciplinary approach including sedimentology, mineralogy and geochemistry, and discussed by McCarthy and Humphries, questions the established model suggesting that the alkaline water cannot derive from simple concentration of the floodwater.
Key Points
The chemical composition of the alkaline groundwater cannot reflect simple evaporation processes
The variable origin of islands in the Okavango Delta makes for variable bio‐geochemical processes
The hydro‐geochemical functioning of the Delta will only be understood through interdisciplinary studies
Balancing urban development with environmental sustainability is a major challenge that is increasingly recognized in planning decisions. Urban development proposals are often approved with the ...expectation that deleterious impacts on native species will be constrained, but this assumption is rarely tested over sufficient timelines to confirm its validity for long‐lived, at‐risk species. We tracked changes in Blanding's turtle (Emydoidea blandingii) habitat availability and demography over 10 years near Ottawa, ON, Canada, to determine whether urban development and associated mitigation measures were sufficient to ensure long‐term population persistence. Suitable turtle habitat declined by 10% during the study, and wetland corridors were essentially lost. Habitat loss coincided with a marked reduction in adult turtle apparent survival, resulting in a 70% decline in population size. Adult females experienced the greatest decline, and despite wildlife fencing and culvert placement as conditions of project approval, turtle road mortality likely was the primary cause of the decline. Deterministic population viability analysis revealed that ~4 adult female road mortalities (of an initial 56 females) per year produced a comparable decline to that observed in our population estimates; at this rate, the population will likely breach its quasi‐extinction threshold (4 females) in under a decade. Accordingly, we infer that in our study area, approved urban development was not compatible with at‐risk turtle population viability. Our findings imply that urban development approval conditions, even when conducted in the context of seemingly robust species‐at‐risk protection, can be inadequate to ensure sustainability. We contend that if environmental sustainability is to be prioritized, urban development projects in areas occupied by at‐risk species must be subject to more stringent oversight during the planning, approval and implementation phases.
Balancing urban development with environmental sustainability is a major challenge in planning decisions, especially with regards to long‐lived, at‐risk species. We tracked changes in Blanding's turtle habitat and demography over 10 years near Ottawa, ON, Canada, to determine the impacts of urban development on long‐term population persistence. Suitable turtle habitat declined by 10% during the study, which coincided with a marked reduction in adult turtle apparent survival, resulting in a 70% decline in population size. Adult females experienced the greatest decline, and despite mitigation measures to offset negative impacts, turtle road mortality likely was the primary cause of the decline. Population viability analysis revealed that four adult female road mortalities per year could have led to this decline; at his rate, the population will likely breach its quasi‐extinction threshold in under a decade. We infer that in our study area, urban development was not compatible with turtle population viability.
We report the discovery of 76 new T dwarfs from the UKIRT Infrared Deep Sky Survey (UKIDSS) Large Area Survey (LAS). Near-infrared broad- and narrow-band photometry and spectroscopy are presented for ...the new objects, along with Wide-field Infrared Survey Explorer (WISE) and warm-Spitzer photometry. Proper motions for 128 UKIDSS T dwarfs are presented from a new two epoch LAS proper motion catalogue. We use these motions to identify two new benchmark systems: LHS 6176AB, a T8p+M4 pair and HD 118865AB, a T5.5+F8 pair. Using age constraints from the primaries and evolutionary models to constrain the radii, we have estimated their physical properties from their bolometric luminosity. We compare the colours and properties of known benchmark T dwarfs to the latest model atmospheres and draw two principal conclusions. First, it appears that the H − 4.5 and J − W2 colours are more sensitive to metallicity than has previously been recognized, such that differences in metallicity may dominate over differences in T
eff when considering relative properties of cool objects using these colours. Secondly, the previously noted apparent dominance of young objects in the late-T dwarf sample is no longer apparent when using the new model grids and the expanded sample of late-T dwarfs and benchmarks. This is supported by the apparently similar distribution of late-T dwarfs and earlier type T dwarfs on reduced proper motion diagrams that we present. Finally, we present updated space densities for the late-T dwarfs, and compare our values to simulation predictions and those from WISE.
We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients.
The Systemic Lupus International ...Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality.
We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point).
Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.
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