Outcome of all-inside second-generation meniscal repair: Minimum five-year follow-up

BACKGROUND: Meniscal repair and preservation are the goal, when possible, of the treatment of meniscal injury. Current research on second-generation all-inside repair systems has been limited to a maximum of three years of follow-up. The purpose of this study was to evaluate the mid-term clinical success (at more than five years) of meniscal repair performed with a second-generation all-inside repair device, both as an isolated procedure and with a concomitant anterior cruciate ligament (ACL) reconstruction. METHODS: This is a retrospective review of patients who underwent meniscal repair with use of the all-inside FAST-FIX Meniscal Repair System (Smith & Nephew Arthroscopy, Andover, Massachusetts) from December 1999 to January 2007. Eighty-three meniscal repairs (in eighty-one patients) were identified, and follow-up data were obtained for seventy-five (90%). Twenty-six (35%) of the meniscal repairs were performed as isolated procedures. Clinical failure was defined as repeat surgical intervention involving resection or revision repair. Clinical outcomes were also assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, and the Marx activity score. RESULTS: The minimum duration of follow-up was five years (average, seven years). Twelve patients (16%) had failure of the meniscal repair, at an average of forty-seven months (range, fifteen to ninety-five months). The data did not offer enough statistical evidence, at alpha = 0.05, to establish a difference in average patient age, patient sex, or number of sutures utilized between successful repairs and failures. There was no difference in the failure rate between isolated repairs (12%; 95% confidence interval [CI]: −0.76% to 23.76%) and those performed with concurrent ACL reconstruction (18%; 95% CI: 7.47% to 29.13%), and the average time to failure was similar between these two groups (48.1 months versus 46.6 months, p = 0.939). Postoperative KOOS and IKDC outcome scores were also similar between the groups. CONCLUSIONS: This report of mid-term follow-up results of primary second-generation all-inside meniscal repair demonstrates its effectiveness both as an isolated procedure and when it is performed with concurrent ACL reconstruction. After a minimum of five years of follow-up, 84% of the patients continued to demonstrate successful repair. Treatment success was further supported by favorable results on patient-based outcome measures. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Disk-Jet Connection in the Radio Galaxy 3C 120

We present the results of extensive multi-frequency monitoring of the radio galaxy 3C 120 between 2002 and 2007 at X-ray, optical, and radio wave bands, as well as imaging with the Very Long Baseline Array (VLBA). Over the 5 yr of observation, significant dips in the X-ray light curve are followed by ejections of bright superluminal knots in the VLBA images. Consistent with this, the X-ray flux and 37 GHz flux are anti-correlated with X-ray leading the radio variations. This implies that, in this radio galaxy, the radiative state of accretion disk plus corona system, where the X-rays are produced, has a direct effect on the events in the jet, where the radio emission originates. The X-ray power spectral density of 3C 120 shows a break, with steeper slope at shorter timescale and the break timescale is commensurate with the mass of the central black hole based on observations of Seyfert galaxies and black hole X-ray binaries. These findings provide support for the paradigm that black hole X-ray binaries and active galactic nuclei are fundamentally similar systems, with characteristic time and size scales linearly proportional to the mass of the central black hole. The X-ray and optical variations are strongly correlated in 3C 120, which implies that the optical emission in this object arises from the same general region as the X-rays, i.e., in the accretion disk-corona system. We numerically model multi-wavelength light curves of 3C 120 from such a system with the optical-UV emission produced in the disk and the X-rays generated by scattering of thermal photons by hot electrons in the corona. From the comparison of the temporal properties of the model light curves to that of the observed variability, we constrain the physical size of the corona and the distances of the emitting regions from the central BH.Comment: Accepted for publication in the Astrophysical Journal. 28 pages, 21 figures, 2 table

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Operational Ontology for Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical and Research Use of Real-World Data From Patients Treated for Cancer

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships. METHODS AND MATERIALS: The American Association of Physicists in Medicine\u27s Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders\u27 collective experience of issues that typically compromise the formation of large inter- and intra-institutional databases from EHRs. The Big Data Science Committee adopted an iterative, cyclical approach to engaging stakeholders beyond its membership to optimize the integration of diverse perspectives from the community. RESULTS: We developed the Operational Ontology for Oncology (O3), which identified 42 key elements, 359 attributes, 144 value sets, and 155 relationships ranked in relative importance of clinical significance, likelihood of availability in EHRs, and the ability to modify routine clinical processes to permit aggregation. Recommendations are provided for best use and development of the O3 to 4 constituencies: device manufacturers, centers of clinical care, researchers, and professional societies. CONCLUSIONS: O3 is designed to extend and interoperate with existing global infrastructure and data science standards. The implementation of these recommendations will lower the barriers for aggregation of information that could be used to create large, representative, findable, accessible, interoperable, and reusable data sets to support the scientific objectives of grant programs. The construction of comprehensive real-world data sets and application of advanced analytical techniques, including artificial intelligence, holds the potential to revolutionize patient management and improve outcomes by leveraging increased access to information derived from larger, more representative data sets

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Peer reviewe

Measurement of the F2 structure function in deep inelastic e+^{+}p scattering using 1994 data from the ZEUS detector at HERA

We present measurements of the structure function \Ft\ in e^+p scattering at HERA in the range 3.5\;\Gevsq < \qsd < 5000\;\Gevsq. A new reconstruction method has allowed a significant improvement in the resolution of the kinematic variables and an extension of the kinematic region covered by the experiment. At \qsd < 35 \;\Gevsq the range in x now spans 6.3\cdot 10^{-5} < x < 0.08 providing overlap with measurements from fixed target experiments. At values of Q^2 above 1000 GeV^2 the x range extends to 0.5. Systematic errors below 5\perc\ have been achieved for most of the kinematic urray, W

Comparison of ZEUS data with standard model predictions for e+p→e+Xe^+ p \rightarrow e^+ X scattering at high xx and Q2Q^2

Using the ZEUS detector at HERA, we have studied the reaction e(+)p --> e(+)X for Q(2) > 5000 GeV2 with a 20.1 pb(-1) data sample collected during the years 1993 to 1996. For Q(2) below 15000 GeV2, the data are in good agreement with Standard Model expectations. For Q(2) > 35000 GeV2. two events are observed while 0.145 +/- 0.013 events are expected, A statistical analysis of a large ensemble of simulated Standard Model experiments indicates that with probability 6.0%, an excess at least as unlikely as that observed would occur above some Q(2) cut. For x > 0.55 and y > 0.75, four events are observed where 0.91 +/- 0.08 events are expected, A statistical analysis of the two-dimensional distribution of the events in x and y yields a probability of 0.72% for the region x > 0.55 and y > 0.25 and a probability of 7.8% for the entire Q(2) > 5000 GeV2 data sample. The observed excess above Standard Model expectations is particularly interesting because it occurs in a previously unexplored kinematic region

Measurement of Elastic ϕ\phi Photoproduction at HERA

The production of $\phi$ mesons in the reaction $e^{+}p \rightarrow e^{+} \phi p$ ($\phi \rightarrow K^{+}K^{-}$) at a median $Q^{2}$ of $10^{-4} \ \rm{GeV^2}$has been studied with the ZEUS detector at HERA. The differential$\phi$photoproduction cross section$d\sigma/dt$has an exponential shape and has been determined in the kinematic range$0.1<|t|<0.5 \ \rm{GeV^2}$and$60 < W < 80 \ \rm{GeV}$. An integrated cross section of$\sigma_{\gamma p \rightarrow \phi p} = 0.96 \pm 0.19^{+0.21}_{-0.18}$$\rm{\mu b}$has been obtained by extrapolating to {\it t} = 0. When compared to lower energy data, the results show a weak energy dependence of both$\sigma_{\gamma p \rightarrow \phi p}$and the slope of the$t$distribution. The$\phi$decay angular distributions are consistent with$s$-channel helicity conservation. From lower energies to HERA energies, the features of$\phi$ photoproduction are compatible with those of a soft diffractive process.Comment: 23 pages, including 6 post script figure