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The subscapularis (SSc) is the most powerful muscle of the rotator cuff. His role in shoulder stability and shoulder motion is well studied and due to functional and frequent association with concomitant other lesions, the repair of the SSc tendon is always desirable to restore force and stability to the shoulder.

Objective To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. Methods Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. Results A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). Conclusion A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

Intrauterine devices, including levonorgestrel-releasing and copper devices, are highly effective long-acting reversible contraceptives. The potential risks associated with intrauterine devices are low and include uterine perforation and device expulsion.This study aimed to evaluate the risk of perforation and expulsion associated with levonorgestrel-releasing devices vs copper devices in clinical practice in the United States.The Association of Perforation and Expulsion of Intrauterine Device study was a retrospective cohort study of women aged ≤50 years with an intrauterine device insertion during 2001 to 2018 and information on intrauterine device type and patient and medical characteristics. Of note, 4 research sites with access to electronic health records contributed data for the study: 3 Kaiser Permanente-integrated healthcare systems (Northern California, Southern California, and Washington) and 1 healthcare system using data from a healthcare information exchange in Indiana (Regenstrief Institute). Perforation was classified as any extension of the device into or through the myometrium. Expulsion was classified as complete (not visible in the uterus or abdomen or patient reported) or partial (any portion in the cervix or malpositioned). We estimated the crude incidence rates and crude cumulative incidence by intrauterine device type. The risks of perforation and expulsion associated with levonorgestrel-releasing intrauterine devices vs copper intrauterine devices were estimated using Cox proportional-hazards regression with propensity score overlap weighting to adjust for confounders.Among 322,898 women included in this analysis, the incidence rates of perforation per 1000 person-years were 1.64 (95% confidence interval, 1.53-1.76) for levonorgestrel-releasing intrauterine devices and 1.27 (95% confidence interval, 1.08-1.48) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 0.22% (95% confidence interval, 0.20-0.24) and 0.63% (95% confidence interval, 0.57-0.68) for levonorgestrel-releasing intrauterine devices and 0.16% (95% confidence interval, 0.13-0.20) and 0.55% (95% confidence interval, 0.44-0.68) for copper intrauterine devices, respectively. The incidence rates of expulsion per 1000 person-years were 13.95 (95% confidence interval, 13.63-14.28) for levonorgestrel-releasing intrauterine devices and 14.08 (95% confidence interval, 13.44-14.75) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 2.30% (95% confidence interval, 2.24-2.36) and 4.52% (95% confidence interval, 4.40-4.65) for levonorgestrel-releasing intrauterine devices and 2.30% (95% confidence interval, 2.18-2.44) and 4.82 (95% confidence interval, 4.56-5.10) for copper intrauterine devices, respectively. Comparing levonorgestrel-releasing intrauterine devices with copper intrauterine devices, the adjusted hazard ratios were 1.49 (95% confidence intervals, 1.25-1.78) for perforation and 0.69 (95% confidence intervals, 0.65-0.73) for expulsion.After adjusting for potential confounders, levonorgestrel-releasing intrauterine devices were associated with an increased risk of uterine perforation and a decreased risk of expulsion relative to copper intrauterine devices. Given that the absolute numbers of these events are low in both groups, these differences may not be clinically meaningful.

Type II diabetes mellitus (T2DM) is characterized by the presence of amyloid deposits of the human islet amyloid polypeptide (hIAPP) in pancreatic beta-cells. A wealth of data supports the hypothesis that hIAPP's toxicity is related to an abnormal interaction of amyloids with islet cell membranes. Thus, many studies aimed at finding effective therapies for T2DM focus on the design of molecules that are able to inhibit hIAPP's amyloid growth and the related membrane damage as well. Based on this view and inspired by its known anti-amyloid properties, we have functionalized resveratrol with a phosphoryl moiety (4'-O-PR) that improves its solubility and pharmacological properties. A second resveratrol derivative has also been obtained by conjugating resveratrol with a dimyristoylphosphatidyl moiety (4'-DMPR). The use of both compounds resulted in abolishing both amyloid growth and amyloid mediated POPC/POPS membrane damage in tube tests. We propose that a mixture of a water-soluble anti-aggregating compound and its lipid-anchored derivative may be employed as a general strategy to prevent and/or to halt amyloid related membrane damage.

X-ray absorption spectroscopy (XAS) is a powerful method for obtaining electronic and structural information around a well-defined absorbing atom site of different types of matter, from biological systems to condensed materials in almost all possible thermodynamics conditions. The low energy part of the XAS spectrum, from the rising edge up to few hundreds eV, the so called XANES (X-ray absorption near-edge structure) region, is extremely rich of electronic and structural information, like, for example, the oxidation state, overall symmetry, interatomic distances and angles . In this paper we present in details the MXAN method and a new reengineered release of the code proposed in the literature some years ago which allows a complete fit of the XANES energy region in term of well-defined set of structural parameters. This approach is based on the comparison between experimental data and many theoretical calculations performed by varying selected structural parameters starting from a putative structure, i.e. from a well-defined initial geometrical configuration around the absorber. The X-ray photo-absorption cross sections are derived using full multiple-scattering theory, i.e. the scattering path operator is calculated exactly without any series expansion. In this way the analysis can start from the edge without any limitations in the energy range and polarization conditions. Here we present in detail the theoretical background behind the code and new capabilities implemented from theory in this last version of the program as the analysis of XANES data coming from time-dependent spectra. The code is provided with modern technology for rapid deployment of binaries based on Docker runtime so that, without source compiling, its execution reduces to just a command line striking for a full parallel (shared memory) run even using complex construct like memory filesystem in a transparent way to the end-user. Program summary Program Title: MXAN CPC Library link to program files: https://doi.org/10.17632/4k9363vcvh.1 Licensing provisions: GPLv3 Programming language: FORTRAN90 External routines/libraries: MKL or OpenBLAS library Nature of problem: In MXAN (Minuit XANES) program we implemented a fitting procedure based on a full Multiple Scattering (MS) theory [1] able to extract local structural information around the absorbing atom from experimental XANES data. The MXAN method has been successfully used for studying many known and unknown molecular systems, yielding structural geometries and metrics comparable to X-ray diffraction and/or EXAFS results [2] , [3] , [4] . The release of this new code paves the route to new possibilities available now in the latest version of the program, as the analysis of XANES data coming from time-dependent and structural disordered systems. Solution method: MXAN program is based on the comparison between experimental data and iterative theoretical calculations performed by varying selected structural parameters starting from a well-defined initial geometrical configuration around the absorber. The calculation of XANES spectra is performed within the so-called full MS approach, i.e. the inverse of the scattering path operator is computed exactly, avoiding any “a-priori” selection of the relevant MS paths [5] , [6] . The fit procedure is performed in the energy space without the use of any Fourier transform algorithm; polarized spectra can be easily analyzed because the calculation is performed using the full MS approach [1] . The optimization in the space of the parameters is achieved using the CERN-library MINUIT [7] routines minimizing the square residual. Additional comments including restrictions and unusual features: Depending on the molecular system under study and on the operating runtime conditions the program may or may not fit into available host RAM memory. The present release of the code is limited to a single SMP machine by running in parallel using OpenMP and/or the multi-threaded version of MKL or OpenBLAS.

Background Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006–2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration–mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device–related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. Objective We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. Study Design APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. Results The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74–177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. Conclusion Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

We study the contractual design problem of a seller that observes an ex-post signal correlated with the buyer’s valuation and can make the allocation, but not payments, contingent on it. We show that, to maximize her profit, the seller should offer a menu of contracts whereby the good is transferred to the buyer only if the signal is sufficiently low. The welfare implications of these contracts are also discussed.

We study the properties of simple mobile broadband Internet plans characterized by a data cap and an up-front price. Assuming demand uncertainty and a positive correlation between users’ valuations and (expected) demands, we show that a monopolistic provider does always find it convenient to offer one plan with binding cap together with an unlimited one. We characterize all the elements of the profit-maximizing plans, showing that medium users, but not heavy users, will incur the risk of being capped, and that, relative to the benchmark case of unlimited access only, the introduction of a plan with cap leads to a redistribution of surplus from high users to low users. The overall effect on social welfare and users’ surplus is, in general, ambiguous, but is certainly negative if low valuation users have a sufficiently homogeneous demand for Internet traffic.

Italian Brown is a cattle breed largely exploited in the production of many dairy products in Italy, including typical and traditional cheeses. For this reason, the improvement of selection methods is of economic relevance while a deeper understanding of the genetic mechanisms regulating milk production is of general scientific interest. We selected a total of 561 samples, representing virtually all Italian Brown bull population, to test for association between milk production traits and 29 known genes harbouring 106 single nucleotide polymorphisms (SNPs). After filtering, a total of 31 SNPs in 22 candidate genes and 473 bulls were retained. Associations between each SNP and milk traits were tested by a mixed model approach, obtaining seven significantly associated SNPs, two of which (in β-Lactoglobulin) associated with all traits, and four (in Chemokin receptor I, αs1 casein, k casein, fatty acid synthase, thyroid hormone responsive and Oxytocin prepropetide genes) associated with at least one trait.