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Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1®) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLsPTX) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLsPTX and PTX-containing fluid lipid nanodiscs (nanodiscsPTX). These CLsPTX and nanodiscsPTX show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol% PEG-lipid). Here, we studied the PTX loading, in vivo circulation half-life, and biodistribution of systemically administered CLsPTX and nanodiscsPTX and assessed their ability to induce apoptosis in triple-negative breast cancer-bearing immunocompetent mice. We focused on fluid rather than solid lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol% of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLsPTX and nanodiscsPTX was able to incorporate up to 2.5 mol% PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol% PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol% (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy., This research study was supported by the National Institutes of Health under award R01GM130769 (CRS, KKE, WF; mechanistic studies on developing lipid nanoparticles for drug delivery), the European Regional Development Fund (TT, Project No. 2014-2020.4.01.15-0012), the Estonian Research Council (TT, grants PRG230 and EAG79; PS, grant PSG38; LSG, grant MOBJD11), EuronanomedII projects ECM-CART and iNanoGun (TT), H2020 MSCA-RISE project Oxigenated (TT), and the Spanish Ministry of Science and Innovation grants RYC2020-028754-I and PID2021-122364OA-I00 (PS). Partial support was provided by the US National Science Foundation (NSF) under Award DMR-1807327 (CRS; kinetic phase behavior of cationic vesicles with incorporated hydrophobic molecules).

Accretion and erosion of scleractinian (stony coral) carbonate skeletons determine whether a colony will increase or decrease in size with potential consequences for ecosystem processes, functions and services. The capacity for skeletal growth can be estimated by comparing a colony's rate of calcification with its rate of erosion. Calcification depends on the species-specific metabolic activity of living tissue, and erosion depends primarily on the availability and density of barren skeleton, those areas on the colony where polyps have died. Assessment of skeletal growth capacity requires data on calcification rates, erosion rates and both live and barren colony surface area. Rates of calcification and erosion are documented for many Caribbean species and others can be estimated from existing data. Three-dimensional surface area of colonies can be determined from data collected during demographic surveys, which identify species, measure dimensions, and estimate the proportion of live tissue on a colony. Data from demographic surveys conducted in the U.S. Virgin Islands are used to calculate the skeletal growth capacity (GC) as an indicator of coral species and community resilience. Scleractinia are the primary architects of coral reefs, and the gain or loss of skeletal framework is vitally important to reef ecosystem processes that lead to valued goods and services. Estimates of GC reflect stony coral resilience, which is the capacity to recover from disturbances by returning to previous physical and functional levels. GC can also provide insight to the effects of stressors such as ocean acidification, and can inform several management decisions, including restoration site selection and threatened species designation.

OBJECTIVE Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. RESEARCH DESIGN AND METHODS This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. RESULTS Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease–related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease–related factors were predominant for diabetes occurring after pancreatitis. CONCLUSIONS Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.

Background & Aims Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP. Methods We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy. Results The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs 26.4%; P = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [CI], 1.15–1.45), female sex (OR, 3.08; 95% CI, 1.75–5.43), white race (OR, 2.68; 95% CI, 1.20–6.01), and underweight body mass index category (OR, 7.40; 95% CI, 1.56–34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and other patient and disease-related features of CP. Conclusion In the largest study of patients with CP who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP. ClinicalTrials.gov number, NCT03099850.

Return to Intended Oncologic Treatment (RIOT) has been proposed as a quality metric in the care of cancer patients. We sought to define factors associated with inability to RIOT in Pancreatic Ductal Adenocarcinoma (PDAC) patients.The NCDB was queried for patients who underwent pancreaticoduodenectomy for pathologic stage IB, IIA, or IIB PDAC from 2010 to 2016. Multivariable binary logistic regression models identified factors associated with failure to RIOT, and Kaplan-Meier survival analysis and Cox multivariable regression models demonstrated the impact of failure to RIOT on survival.Increasing age (p .001), Hispanic race (p = .002), pathological stage IB (p = .004) and IIA (p = .001) as compared to IIB, increasing hospital stay (p .001), and open surgical approach (p = .024) were associated with increased risk of inability to RIOT. Male sex (p .001), Charlson-Deyo scores of 0 (p .001) and 1 (p = .001) as compared to2, negative surgical margins (p = .048), receiving care at academic institutions (p = .001), and increasing institutional case volume (p = .001) were associated with improved odds of RIOT.Patient features can impact RIOT and should be considered when designing multi-modality treatment strategies.

Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.

Although there are effective treatments that promote recovery and improve quality of life for serious mental illness in nonincarcerated populations, more research is needed to understand the recovery process for individuals with a history of incarceration. A qualitative, grounded theory study was conducted with 17 men and women who have serious mental illness (SMI) and a history of incarceration. Findings revealed barriers and facilitators to the recovery process in the areas of identity, treatment, relationships, community, and institutions. The findings suggested that incarceration had harmful effects on the recovery process for individuals with SMI, although these individuals, at times, found ways to turn this challenging experience into an opportunity for personal growth. The clinical implications of these findings include the importance of the prevention of incarceration for people with SMI, as well as the provision of multidisciplinary care, such as medical, mental health, and substance use treatment, during and after incarceration, to reduce barriers and increase recovery outcomes. Additionally, factors related specifically to incarceration should be addressed during delivery of treatment and accessibility of community resources. Advocacy and policy change for prison reform will also be discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF.The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach.A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P.001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone.In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

Selective enrichment process of CAR- and CAR+ transgenic sub-populations

Consolidated supplementary tables for nanostring data

Supplementary Results and Methods - PDF file 255K, Additional information on results and methods

Supplementary Figure 1 - PDF file 147K, Additional evidence that miR-198 is regulated by MSLN in PC cells

Purpose:Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS).Experimental Design:A multimodality chelator (MMC) was used as a “radioactive linker” to synthesize the fluorescently labeled somatostatin analog, 67/68Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso- and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs.Results:Direct labeling with 67Ga/68Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings.Conclusions:The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.

Supplementary Figure 3 - PDF file 142K, miR-198 modulation in stable cell lines

Supplementary Figure 4 - PDF file 269K, Additional evidence that miR-198 targets the PBX-1/VCP axis

Supplementary Figure 2 - PDF file 207K, PBX-1 and VCP are predicted targets for miR-198

Supplementary Figure 6 - PDF file 388K, miR-198 modulation reduces the tumorigenic functions of mesothelin-overexpressing pancreatic cancer cells in vitro and in vivo

Given the high fatality rate of pancreatic cancer, an effective treatment for this devastating disease is urgently needed. We have shown that mesothelin expression was higher in human pancreatic cancer cells than in human pancreatic duct epithelial cells, and mesothelin mRNA was substantially overexpressed in 18 of 21 (86%) clinical pancreatic adenocarcinoma specimens when compared with the surrounding normal tissues. However, the biological functions of mesothelin in tumor progression are not clearly understood. Here we studied the effects of mesothelin overexpression in pancreatic cancer cell proliferation and migration in vitro and pancreatic cancer progression in vivo. We found that forced expression of mesothelin significantly increased tumor cell proliferation and migration by 90% and 300%, respectively, and increased tumor volume by 4-fold in the nude mice xenograft model when compared with the vector control cell line. Silencing of mesothelin inhibited cell proliferation and migration in pancreatic cancer cells and ablated tumor progression in vivo. Vaccination with chimeric virus-like particles that contain human mesothelin substantially inhibited tumor progression in C57BL/6J mice. The increases in mesothelin-specific antibodies and CTL activity and the decrease in regulatory T cells correlated with reduced tumor progression and prolonged survival. This study revealed novel functions of mesothelin and suggested a new therapeutic vaccine strategy whereby mesothelin is targeted to control pancreatic cancer progression. [Mol Cancer Ther 2008;7(2):286–96]

Supplementary Material from Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer

Purpose: The majority of pancreatic cancers overexpress mesothelin (MSLN), which contributes to enhanced proliferation, invasion, and migration. However, the MSLN regulatory network is still unclear. Here, we investigated the regulation of a panel of tumorigenic factors and explored the potential of MSLN-regulated miR-198 treatment in vivo.Experimental Design: The expression and functional regulation of the tumorigenic factors MSLN, NF-κB, and the homeobox transcription factors (TF) POU2F2 (OCT-2), Pre-B-cell leukemia homeobox factor 1 (PBX-1), valosin-containing protein (VCP), and miR-198 were studied in pancreatic cancer cell lines, patient tumor samples, and xenograft pancreatic cancer mouse models.Results: We found that miR-198 is downregulated in pancreatic cancer and is involved in an intricate reciprocal regulatory loop with MSLN, which represses miR-198 through NF-κB–mediated OCT-2 induction. Furthermore, miR-198 repression leads to overexpression of PBX-1 and VCP. The dysregulated PBX-1/VCP axis leads to increased tumorigenicity. Reconstitution of miR-198 in pancreatic cancer cells results in reduced tumor growth, metastasis, and increased survival through direct targeting MSLN, PBX-1, and VCP. Most interestingly, reduced levels of miR-198 in human tissue samples are associated with upregulation of these tumorigenic factors (MSLN, OCT-2, PBX-1, VCP) and predict poor survival. Reduced miR-198 expression links this tumor network signature and prognosticates poor patient outcome. High miR-198 disrupts the network and predicts better prognosis and increased survival.Conclusions: miR-198 acts as a central tumor suppressor and modulates the molecular makeup of a critical interactome in pancreatic cancer, indicating a potential prognostic marker signature and the therapeutic potential of attacking this tumorigenic network through a central vantage point. Clin Cancer Res; 19(21); 5901–13. ©2013 AACR.

Supplementary figures and tables. "Clean" version.

Supplementary Figure 5 - PDF file 212K, Construct details for miR-198 target analysis of MSLN CDS

Purpose: Zinc levels have been correlated with cancer risk, although the role of zinc and zinc transporters in cancer progression is largely unknown. We recently found that a zinc transporter, ZIP4, is overexpressed in pancreatic cancer. In this study, we further deciphered the role that ZIP4 plays in a pancreatic cancer mouse model by silencing ZIP4.Experimental Design: ZIP4 stable silencing was established in pancreatic cancer cell lines ASPC-1 (ASPC-shZIP4) and BxPC-3 (BxPC-shZIP4) by short hairpin RNA using retrovirus vectors. The stable cells were characterized in vitro and in vivo using a nude mouse xenograft model.Results: Silencing of ZIP4 was associated with decreased cell proliferation, migration, and invasion. Both ASPC-shZIP4 and BxPC-shZIP4 cells showed a significant reduction in tumor volume and weight in the s.c. model, and decreased primary tumor weight in the orthotopic model compared with the vector control cells (ASPC-shV and BxPC-shV). Silencing of ZIP4 also caused reduced incidence of tumor metastasis in the mice and downsized the tumor grade. More importantly, silencing of ZIP4 significantly increased the survival rate of nude mice with orthotopic xenografts (P = 0.005). All ASPC-shZIP4–injected mice (100%) remained alive up to 32 days after tumor implantation, whereas only 30% of the ASPC-shV mice were alive at the same time point. CyclinD1 expression was decreased in the ASPC-shZIP4 xenografts.Conclusions: These results identify a previously uncharacterized role of ZIP4 in pancreatic cancer progression, and indicate that knocking down ZIP4 by short hairpin RNA might be a novel treatment strategy for pancreatic cancers with ZIP4 overexpression. (Clin Cancer Res 2009;15(19):5993–6001)

Supplementary Figure 7 - PDF file 166K, Real-time RT-PCR shows the mRNA levels of all the factors in the proposed network and Linear regression analyses depict the correlations between each factor and its counterparts

Supplementary Data from Down-regulation of ZIP4 by RNA Interference Inhibits Pancreatic Cancer Growth and Increases the Survival of Nude Mice with Pancreatic Cancer Xenografts

Broadly stated, this book makes the case for a different way of thinking about how to measure and manage person-centered outcomes in health care. The basic contrast is between statistical and metrological definitions of measurement. The mainstream statistical tradition focuses attention on numbers in centrally planned and executed data analyses, while metrology focuses on distributing meaningfully interpretable instruments throughout networks of end users. The former approaches impose group-level statistics from the top down in homogenizing ways. The latter tracks emergent patterns from the bottom up, feeding them back to end users in custom tailored applications, whose decisions and behaviors are coordinated by means of shared languages. New forms of information and knowledge necessitate new forms of social organization to create them and put them to use. The chapters in this book describe the analytic, design, and organizational methods that have the potential to open up exciting new possibilities for systematic and broad scale improvements in health care outcomes.

A research program investigating correctable issues in Functional Binocular Vision (FBV) related optometric variables to responses from a symptom survey and reading test results. The study was mounted with no explicit attention to measurement modeling. Data from this research program were retrospectively analyzed with the aims of evaluating the potential for learning from the existing observations, and for improving the study design in future iterations. Results suggest that the physical and psychological measurements of vision combine into a model of FBV that could be standardized and deployed for use in diagnosing significant numbers of untreated vision problems negatively impacting learning outcomes.

Background: The association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored. Methods: In total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003-2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated blood loss and clinically relevant pancreatic fistula occurrence. The study was powered to detect a 33% clinically relevant pancreatic fistula increase in the high estimated blood loss group, with a = 0.05 and b = 0.2. Results: The propensity score model included 966 patients with high estimated blood loss and 966 patients with lower estimated blood loss; all covariate imbalantces were solved. Patients with high estimated blood loss patients experienced higher clinically relevant pancreatic fistula rates (19.4 vs 12.6%, odds ratio 1.66; P < .001), as well as higher severe complication rates (27.8 vs 15.6%), transfusions (50.1 vs 14.3%), reoperations (9.2 vs 4.0%), intensive care unit transfers (9.9 vs 4.8%) and 90-day mortality (4.7 vs 2.0%, all P < .001). High estimated blood loss was an independent predictor for clinically relevant pancreatic fistula (odds ratio 1.78, 95% confidence interval 1.37-2.32), as were prophylactic Octreotide administration (odds ratio 1.95, 95% confidence interval 1.46-2.61) and soft pancreatic texture (odds ratio 5.32, 95% confidence interval 3.74-5.57; all P < .001). Moreover, a second model including 1,126 pancreatoduodenectomies was derived including vascular resections as additional confounder (14.0% vascular resections performed in each group). On multivariable regression, high estimated blood loss was confirmed an independent predictor for clinically relevant pancreatic fistula reduction (odds ratio 1.80, 95% confidence interval 1.32-2.4 4; P < .001), whereas vascular resection was not (odds ratio 0.64, 95% confidence interval 0.34-1.88; P 1/4 .156). Conclusion: This study better establishes the relationship between estimated blood loss and outcomes after pancreatoduodenectomy. Despite inherent contributions to blood loss, its minimization is an actionable opportunity for clinically relevant pancreatic fistula reduction and performance optimization in pancreatoduodenectomy. Accordingly, practical insights are offered to achieve this goal. (c) 2021 Elsevier Inc. All rights reserved.

Objective To provide guidance on culturally competent contraception counselling that is free of coercion and promotes shared decision-making and patient autonomy. Target population Individuals of reproductive age who seek contraception or counselling for family planning. Options Contraception counselling is provided within a rights-based family planning framework, where the individual's beliefs, culture, preferences, and ability to use the chosen method are respected. Outcomes To promote patient autonomy in decision-making surrounding family planning, including the right to access and use their contraceptive method of choice, to decline contraception or use less effective methods of contraception, and to freely choose to discontinue a method of contraception, as well as the right to unbiased, non-coercive contraception counselling and evidence-based information from their health care provider Benefits, Harms, and Costs Implementation of these recommendations would reduce real or perceived coercive contraceptive care, particularly among vulnerable populations, resulting in improved patient autonomy and a better patient experience in health care settings. Evidence Databases searched: MEDLINE, Cochrane, PubMed, and CanLII. Medical terms used: contraception, family planning services, informed consent, coercion, decision making, sterilization, permanent contraception, counselling. Legal terms searched: forced sterilization, and aboriginal. Initial search conducted in 2020 and updated in 2021. Intended Audience This committee opinion is intended for health care providers (obstetricians, gynaecologists, family physicians, general surgeons, nurse practitioners, nurses, midwives, undergraduate/postgraduate medical trainees, and other health care providers) who provide sexual and reproductive health services.

RESUME Objectif Fournir des recommandations pour que le counseling contraceptif soit adapte a la culture, n'exerce aucune coercition et favorise la prise de decision partagee et l'autonomie de la patiente. Population cible Les personnes en âge de procreer qui consultent afin d'adopter une methode contraceptive ou d'obtenir des conseils en planification familiale. Options Le counseling contraceptif est offert dans un cadre de planification familiale fonde sur les droits de la personne, dans le respect des croyances, de la culture et des preferences individuelles et de la capacite de la personne a utiliser la methode choisie. Resultats Promouvoir l'autonomie de la patiente dans la prise de decisions concernant la planification familiale, y compris le droit d'obtenir et d'utiliser la methode contraceptive de son choix, de refuser la contraception ou d'utiliser une methode contraceptive moins efficace et de choisir librement de cesser l'utilisation d'une methode contraceptive, tout en s'assurant que le fournisseur de soins de sante lui offre un counseling contraceptif impartial et non coercitif ainsi que des renseignements fondes sur des donnees probantes. Benefices, risques et couts La mise en œuvre des recommandations limiterait la prestation de soins contraceptifs coercitifs, reels ou percus, en particulier chez les populations vulnerables, ce qui se traduirait par une amelioration de l'autonomie et de l'experience de la patiente dans les milieux de soins. Donnees probantes Bases de donnees utilisees : Medline, Cochrane, PubMed et CanLII. Termes medicaux utilises : contraception, family planning services, informed consent, coercion, decision making, sterilization, permanent contraception, counselling. Termes juridiques utilises : forced sterilization et aboriginal. La recherche initiale a ete effectuee en 2020 et mise a jour en 2021. Professionnels concernes : Cette opinion de comite est destinee aux fournisseurs de soins de sante (obstetriciens, gynecologues, medecins de famille, chirurgiens generalistes, infirmieres praticiennes, infirmieres, sages-femmes, stagiaires en medecine [externat, residence et monitorat] et autres fournisseurs de soins) qui offrent des services de sante sexuelle et reproductive.

Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified.Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls.Our results indicate the presence of various differentially expressed proteins, cytokines/chemokines, and a loss of oral bacterial diversity in the saliva of CP patients. The PGE2 levels trend toward elevation in CP patients. Area under the receiver operating characteristic curve models for proteomic, cytokine, and PGE2 assays ranged from 0.59 to 0.90.Collectively, our studies identify a range of putative CP biomarkers and alterations in human saliva requiring further validation. The biomarker discovery approaches we used might lead to identification of biomarkers useful for CP diagnosis and monitoring.

Perineural invasion is a frequent histological finding in pancreatic adenocarcinoma. However, perineural invasion by intraductal papillary mucinous neoplasm (IPMN), a precursor lesion of pancreatic adenocarcinoma, has not been reported so far. We report a unique case of perineural invasion by IPMN in a 60-year-old female who underwent pancreatoduodenectomy for high-risk features of IPMN. Histological evaluation showed increased nerve density in the connective tissue of IPMN with multiple foci of perineural invasion by IPMN. In addition, there was a discrete 2 mm focus of invasive carcinoma that did not show perineural invasion. Chemotherapy was started and the patient is disease-free at 29 months follow up. The case illustrates previously unreported neuroplastic alterations and neutrotropism in benign neoplastic component of a malignant IPMN.

Measurement plays a vital role in the creation of markets, one that hinges on efficiencies gained via universal availability of precise and accurate information on product quantity and quality. Fulfilling the potential of these ideals requires close attention to measurement and the role of technology in science and the economy. The practical value of a strong theory of instrument calibration and metrological traceability stems from the capacity to mediate relationships in ways that align, coordinate, and integrate different firms’ expectations, investments, and capital budgeting decisions over the long term. Improvements in the measurement of reading ability exhibit patterns analogous to Moore’s Law, which has guided expectations in the micro-processor industry for almost 50 years. The state of the art in reading measurement serves as a model for generalizing the mediating role of instruments in making markets for other forms of intangible assets. These remarks provide only a preliminary sketch of the kinds of information that are both available and needed for making more efficient markets for human, social, and natural capital. Nevertheless, these initial steps project new horizons in the arts and sciences of measuring and managing intangible assets.

Rasch’s unidimensional models for measurement show how to connect object measures (e.g., reader abilities), measurement mechanisms (e.g., machine-generated cloze reading items), and observational outcomes (e.g., counts correct on reading instruments). Substantive theory shows what interventions or manipulations to the measurement mechanism can be traded off against a change to the object measure to hold the observed outcome constant. A Rasch model integrated with a substantive theory dictates the form and substance of permissible interventions. Rasch analysis, absent construct theory and an associated specification equation, is a black box in which understanding may be more illusory than not. Finally, the quantitative hypothesis can be tested by comparing theory-based trade-off relations with observed trade-off relations. Only quantitative variables (as measured) support such trade-offs. Note that to test the quantitative hypothesis requires more than manipulation of the algebraic equivalencies in the Rasch model or descriptively fitting data to the model. A causal Rasch model involves experimental intervention/manipulation on either reader ability or text complexity or a conjoint intervention on both simultaneously to yield a successful prediction of the resultant observed outcome (count correct). We conjecture that when this type of manipulation is introduced for individual reader text encounters and model predictions are consistent with observations, the quantitative hypothesis is sustained.

A metrological infrastructure for the social, behavioral, and economic sciences has foundational and transformative potentials relating to education, health care, human and natural resource management, organizational performance assessment, and the economy at large. The traceability of universally uniform metrics to reference standard metrics is a taken-for-granted essential component of the infrastructure of the natural sciences and engineering. Advanced measurement methods and models capable of supporting similar metrics, standards, and traceability for intangible forms of capital have been available for decades but have yet to be implemented in ways that take full advantage of their capacities. The economy, education, health care reform, and the environment are all now top national priorities. There is nothing more essential to succeeding in these efforts than the quality of the measures we develop and deploy. Even so, few, if any, of these efforts are taking systematic advantage of longstanding, proven measurement technologies that may be crucial to the scientific and economic successes we seek. Bringing these technologies to the attention of the academic and business communities for use, further testing, and development in new directions is an area of critical national need.

Huge resources are invested in metrology and standards in the natural sciences, engineering, and across a wide range of commercial technologies. Significant positive returns of human, social, environmental, and economic value on these investments have been sustained for decades. Proven methods for calibrating test and survey instruments in linear units are readily available, as are data- and theory-based methods for equating those instruments to a shared unit. Using these methods, metrological traceability is obtained in a variety of commercially available elementary and secondary English and Spanish language reading education programs in the U.S., Canada, Mexico, and Australia. Given established historical patterns, widespread routine reproduction of predicted text-based and instructional effects expressed in a common language and shared frame of reference may lead to significant developments in theory and practice. Opportunities for systematic implementations of teacher-driven lean thinking and continuous quality improvement methods may be of particular interest and value.

In his classic paper entitled “The Unreasonable Effectiveness of Mathematics in the Natural Sciences,” Eugene Wigner addresses the question of why the language of Mathematics should prove so remarkably effective in the physical [natural] sciences. He marvels that “the enormous usefulness of mathematics in the natural sciences is something bordering on the mysterious and that there is no rational explanation for it.” We have been similarly struck by the outsized benefits that theory based instrument calibrations convey on the natural sciences, in contrast with the almost universal practice in the social sciences of using data to calibrate instrumentation.

Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities.We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile, which captures 7 symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database.Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes, 2.54-7.03) and had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes, 4.08-10.37) and clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, 2.80-5.38).Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP. (ClinicalTrials.gov, Number: NCT03099850).

In 1959, Ragnar Frisch prompted Georg Rasch to formalise a separability theorem that continues today to serve as the basis of a wide range of theoretical and applied developments in psychological and social measurement. Previously unnoted are the influences on Rasch exerted by Frisch’s concerns for data autonomy, model identification and necessary and sufficient conditions. Although Rasch acknowledged Frisch’s prompting towards a separability theorem, he did not acknowledge any substantive, intellectual debt to him, nor to Irving Fisher, but only to Ronald Fisher. Rasch appears to have developed a special interest in sufficiency and identified models when studying with Frisch in 1935, and in 1947, when Rasch accompanied Tjalling Koopmans to the University of Chicago and the Cowles Commission for Research in Economics. I. Fisher’s separation theorem continues to be relevant in econometrics, and interest in Rasch’s separability theorem is growing as the measurement models based on it are adopted in metrological theory and practice. The extensive interrelations between measurement science, metrological standards and economics suggest paths towards lower transaction costs and more efficient markets for individualised exchanges of human, social and natural capital. Equally, if not more, surprising are the implications for a poetic art of complex, harmonised relationships played out via creative improvisations expressed using instruments tuned to shared scales. JEL: B41, C10, C13, C20, C42, D70, E60, H54, I11, I21, I31, P11