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The cervix is a soft tissue exhibiting time-dependent behavior under mechanical loads. The cervix is a vital mechanical barrier to protect the growing fetus. The remodeling of the cervical tissue, characterized by an increase in time-dependent material properties, is necessary for a safe parturition. The failure of its mechanical function and accelerated tissue remodeling is hypothesized to lead to preterm birth, which is birth before 37 weeks of gestation. To understand the mechanism of the time-dependent behavior of the cervix under compressive states, we employ a porous-viscoelastic material model to describe a set of spherical indentation tests performed on nonpregnant and term pregnant tissue. A genetic algorithm-based inverse finite element analysis is used to fit the force-relaxation data by optimizing the material parameters, and the statistical analysis of the optimized material parameters is conducted on different sample groups. The force response is captured well using the porous-viscoelastic model. The indentation force-relaxation of the cervix is explained by the porous effects and the intrinsic viscoelastic properties of the extracellular matrix (ECM) microstructure. The hydraulic permeability obtained from the inverse finite element analysis agrees with the trend of the value directly measured previously by our group. The nonpregnant samples are found significantly more permeable than the pregnant samples. Within nonpregnant samples, the posterior internal os is found significantly less permeable than the anterior and posterior external os. The proposed model exhibits the superior capability to capture the force-relaxation response of the cervix under indentation, as compared to the conventional quasi-linear viscoelastic framework (range of r 2 of the porous-viscoelastic model 0.88-0.98 vs. quasi-linear model: 0.67-0.89). As a constitutive model with a relatively simple form, the porous-viscoelastic framework has the potential to be used to understand disease mechanisms of premature cervical remodeling, model contact of the cervix with biomedical devices, and interpret force readings from novel in-vivo measurement tools such as an aspiration device., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Surgical management of the axilla in patients with clinically node-positive breast cancer has shifted to less invasive surgical approaches, such as sentinel lymph node dissection (SLND) and targeted axillary dissection (TAD). Successful retrieval of the biopsy clip marking the lymph node of interest is crucial for assessment of pathologic response and locoregional disease control., Methods: We performed a retrospective review of patients ≥18 years old with invasive breast cancer and biopsy-proven axillary LN involvement, who underwent LN clip placement from January 2012 to July 2017 at Johns Hopkins Hospital., Results: Of the 128 eligible patients, the median age at diagnosis was 51.5 years (range, 23-92 years) with predominately stage T2-3 disease (54.7% T2, 42.2% T3), of ductal histology (76.6%), and located in the upper outer quadrant (42.2%). Among the 63.3% (81) of patients who received neoadjuvant systemic therapy, 43.2% (35) had a partial response and 30.9% (25) had a complete response. Axillary procedures performed consisted of 36.7% (47) SLND/TAD, 53.9% (69) ALND, and 9.4% (12) SLND/TAD with conversion to ALND. The clipped LN was successfully retrieved in 63.8% (30) of SLND/TADs, 39.1% (27) of ALNDs, and 58.3% (7) of SLND/TADs followed by ALND. Pre-operative node localization by wire and/or skin markings was performed for 16.4% (21) of patients. Among these, 90.5% (19) of clipped LNs were successfully retrieved, compared to 42.1% (45) retrieved in axillary procedures without preoperative node localization., Conclusion: Use of preoperative targeted node localization improved rate of clipped LN retrieval across all three types of axillary procedures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The mechanical function of the uterine cervix is critical for a healthy pregnancy. During pregnancy, the cervix undergoes significant softening to allow for a successful delivery. Abnormal cervical remodeling is suspected to contribute to preterm birth. Material constitutive models describing known biological shifts in pregnancy are essential to predict the mechanical integrity of the cervix. In this work, the material response of human cervical tissue under spherical indentation and uniaxial tensile tests loaded along different anatomical directions is experimentally measured. A deep-learning segmentation tool is applied to capture the tissue deformation during the uniaxial tensile tests. A 3-dimensional, equilibrium anisotropic continuous fiber constitutive model is formulated, considering collagen fiber directionality, fiber bundle dispersion, and the entropic nature of wavy cross-linked collagen molecules. Additionally, the universality of the material model is demonstrated by characterizing previously published mouse cervix mechanical data. Overall, the proposed material model captures the tension-compression asymmetric material responses and the remodeling characteristics of both human and mouse cervical tissue. The pregnant (PG) human cervix (mean locking stretch ζ=2.4, mean initial stiffness ξ=12 kPa, mean bulk modulus κ=0.26 kPa, mean dispersion b=1.0) is more compliant compared with the nonpregnant (NP) cervix (mean ζ=1.3, mean ξ=32 kPa, mean κ=1.4 kPa, mean b=1.4). Creating a validated material model, which describes the role of collagen fiber directionality, dispersion, and crosslinking, enables tissue-level biomechanical simulations to determine which material and anatomical factors drive the cervix to open prematurely. STATEMENT OF SIGNIFICANCE: In this study, we report a 3D anisotropic hyperelastic constitutive model based on Langevin statistical mechanics and successfully describe the material behavior of both human and mouse cervical tissue using this model. This model bridges the connection between the extracellular matrix (ECM) microstructure remodeling and the macro mechanical properties change of the cervix during pregnancy via microstructure-associated material parameters. This is the first model, to our knowledge, to connect the the entropic nature of wavy cross-linked collagen molecules with the mechanical behavior of the cervix. Inspired by microstructure, this model provides a foundation to understand further the relationship between abnormal cervical ECM remodeling and preterm birth. Furthermore, with a relatively simple form, the proposed model can be applied to other fibrous tissues in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Five pediatric residency programs implemented true X + Y scheduling in 2018 where residents have continuity clinic in "blocks" rather than half-day per week experiences. We report the impact X + Y scheduling has on pediatric resident and faculty perceptions of patient care and other educational experiences over a 3-year timeframe., Methods: Electronic surveys were sent to residents and faculty of the participating programs prior to implementing X + Y scheduling and annually thereafter (2018-2021). Survey questions measured resident and faculty perception of continuity clinic schedule satisfaction and the impact of continuity clinic schedules on inpatient and subspecialty rotations. Data were analyzed using z-tests for proportion differences., Results: One hundred and eight six residents were sent the survey preimplementation and 254 to 289 postimplementation with response rates ranging from 47% to 69%. Three hundred and seventy-eight to 395 faculty members were sent the survey with response rates ranging from 26% to 51%. Statistically significant (P < .05) sustained perceived improvements over 3 years with X+Y were seen in outpatient continuity, inpatient workflow, and time for teaching both inpatient and in continuity clinic., Conclusions: X + Y scheduling can lead to perceived improvements in various aspects of pediatric residency programs. Our study demonstrates these improvements have been sustained over 3 years in the participating programs., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

During a normal vaginal delivery, the muscle cells propagate electrical signals throughout the uterine wall, resulting in uterine contractions. However, uncoordinated uterine activity may disturb the uterine contractions pattern and negatively impact fetal and maternal health. Some of the abnormalities identified by the specialists are excessively short resting intervals and tachysystole. This work aims to investigate the influence of abnormal uterine activity in terms of maximum principal stress distribution and collagen fibers stretch in the uterine tissue during vaginal delivery with (i) excessively short resting intervals without changing the contraction time, and (ii) tachysystole (contraction and reduced resting times). These patterns are compared with a normal uterine contraction pattern. To achieve our aims, a biomechanical model was developed, including finite element models of the uterus and the fetus, and an electro-chemo-mechanical constitutive model. Generally, the excessively short resting intervals exhibit higher average maximum principal stresses during the contraction and resting stages, lower average fibers stretch values in the longitudinal direction and higher stretch in the circumferential direction. On the other hand, the tachysystole exhibit generally lower stress values during the uterine contraction and higher stress values during the resting stages, higher stretch in the longitudinal direction, and lower stretch in the circumferential direction., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Variation in lamin A/C results in a spectrum of clinical disease, including arrhythmias and cardiomyopathy. Benign variation is rare, and classification of LMNA missense variants via in silico prediction tools results in a high rate of variants of uncertain significance (VUSs)., Objective: The goal of this study was to use a machine learning (ML) approach for in silico prediction of LMNA pathogenic variation., Methods: Genetic sequencing was performed on family members with conduction system disease, and patient cell lines were examined for LMNA expression. In silico predictions of conservation and pathogenicity of published LMNA variants were visualized with uniform manifold approximation and projection. K-means clustering was used to identify variant groups with similarly projected scores, allowing the generation of statistically supported risk categories., Results: We discovered a novel LMNA variant (c.408C>A:p.Asp136Glu) segregating with conduction system disease in a multigeneration pedigree, which was reported as a VUS by a commercial testing company. Additional familial analysis and in vitro testing found it to be pathogenic, which prompted the development of an ML algorithm that used in silico predictions of pathogenicity for known LMNA missense variants. This identified 3 clusters of variation, each with a significantly different incidence of known pathogenic variants (38.8%, 15.0%, and 6.1%). Three hundred thirty-nine of 415 head/rod domain variants (81.7%), including p.Asp136Glu, were in clusters with highest proportions of pathogenic variants., Conclusion: An unsupervised ML method successfully identified clusters enriched for pathogenic LMNA variants including a novel variant associated with conduction system disease. Our ML method may assist in identifying high-risk VUS when familial testing is unavailable., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The cellular mechanisms required to ensure homeostasis of the hematopoietic niche and the ability of this niche to support hematopoiesis upon stress remain elusive. We here identify Wnt5a in Osterix+ mesenchymal progenitor and stem cells (MSPCs) as a critical factor for niche-dependent hematopoiesis. Mice lacking Wnt5a in MSPCs suffer from stress-related bone marrow (BM) failure and increased mortality. Niche cells devoid of Wnt5a show defective actin stress fiber orientation due to an elevated activity of the small GTPase CDC42. This results in incorrect positioning of autophagosomes and lysosomes, thus reducing autophagy and increasing oxidative stress. In MSPCs from patients from BM failure states which share features of peripheral cytopenia and hypocellular BM, we find similar defects in actin stress fiber orientation, reduced and incorrect colocalization of autophagosomes and lysosomes, and CDC42 activation. Strikingly, a short pharmacological intervention to attenuate elevated CDC42 activation in vivo in mice prevents defective actin-anchored autophagy in MSPCs, salvages hematopoiesis and protects against lethal cytopenia upon stress. In summary, our study identifies Wnt5a as a restriction factor for niche homeostasis by affecting CDC42-regulated actin stress-fiber orientation and autophagy upon stress. Our data further imply a critical role for autophagy in MSPCs for adequate support of hematopoiesis by the niche upon stress and in human diseases characterized by peripheral cytopenias and hypocellular BM., (© 2022 by The American Society of Hematology.)

Objective: A consortium of 8 academic child and adolescent psychiatry programs in the United States and Canada examined their pivot from in-person, clinic-based services to home-based telehealth during the COVID-19 pandemic. The aims were to document the transition across diverse sites and to present recommendations for future telehealth service planning., Method: Consortium sites completed a Qualtrics survey assessing site characteristics, telehealth practices, service use, and barriers to and facilitators of telehealth service delivery prior to (pre) and during the early stages of (post) the COVID-19 pandemic. The design is descriptive., Results: All sites pivoted from in-person services to home-based telehealth within 2 weeks. Some sites experienced delays in conducting new intakes, and most experienced delays establishing tele-group therapy. No-show rates and use of telephony versus videoconferencing varied by site. Changes in telehealth practices (eg, documentation requirements, safety protocols) and perceived barriers to telehealth service delivery (eg, regulatory limitations, inability to bill) occurred pre-/post-COVID-19., Conclusion: A rapid pivot from in-person services to home-based telehealth occurred at 8 diverse academic programs in the context of a global health crisis. To promote ongoing use of home-based telehealth during future crises and usual care, academic programs should continue documenting the successes and barriers to telehealth practice to promote equitable and sustainable telehealth service delivery in the future., (Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The cervix undergoes rapid and dramatic shifts in collagen and elastic fiber structure to achieve its disparate physiological roles of competence during pregnancy and compliance during birth. An understanding of the structure-function relationships of collagen and elastic fibers to maintain extracellular matrix (ECM) homeostasis requires an understanding of the mechanisms executed by non-structural ECM molecules. Small-leucine rich proteoglycans (SLRPs) play key functions in biology by affecting collagen fibrillogenesis and regulating enzyme and growth factor bioactivities. In the current study, we evaluated collagen and elastic fiber structure-function relationships in mouse cervices using mice with genetic ablation of decorin and/or biglycan genes as representative of Class I SLRPs, and lumican gene representative of Class II SLRP. We identified structural defects in collagen fibril and elastic fiber organization in nonpregnant mice lacking decorin, or biglycan or lumican with variable resolution of defects noted during pregnancy. The severity of collagen and elastic fiber defects was greater in nonpregnant mice lacking both decorin and biglycan and defects were maintained throughout pregnancy. Loss of biglycan alone reduced tissue extensibility in nonpregnant mice while loss of both decorin and biglycan manifested in decreased rupture stretch in late pregnancy. Collagen cross-link density was similar in the Class I SLRP null mice as compared to wild-type nonpregnant and pregnant controls. A broader range in collagen fibril diameter along with an increase in mean fibril spacing was observed in the mutant mice compared to wild-type controls. Collectively, these findings uncover functional redundancy and hierarchical roles of Class I and Class II SLRPs as key regulators of cervical ECM remodeling in pregnancy. These results expand our understating of the critical role SLRPs play to maintain ECM homeostasis in the cervix., Competing Interests: Declaration of competing interests The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The cervical remodeling process during pregnancy is characterized by progressive compositional and structural changes in the tissues extra-cellular matrix (ECM). Appropriately timed remodeling is critical for healthy gestation and prevention of premature cervical softening leading to preterm birth (PTB). Modification of the ECM glycosaminoglycans (GAGs) content with advancing pregnancy, especially the non-sulfated GAG hyaluronan (HA), is a fundamental change associated with cervical remodeling. While GAGs have numerous physiological roles, the mechanical consequence of evolving GAG content on cervical structure-function behavior remains an open question. Additionally, an understanding of cervical swelling properties, postulated to be regulated in part by GAGs, is required for the appropriate definition of a reference configuration for mechanical tests and to enhance biological understanding. To investigate cervical swelling, osmotic loading tests are conducted on isolated wild type mouse cervices throughout pregnancy. These tests are performed in various osmolarity solutions to assess the influence of the media on swelling kinetics. A genetically altered strain of mice with depletion of cervical HA is also tested to elucidate the contribution of HA to tissue swelling. Results show ex vivo cervical swelling is significant with volume changes ranging from 20 to 100% after 3h of free swelling. The swelling kinetics depend highly on osmolarity of the media and is altered with advancing pregnancy. The contribution of HA to swelling is only significant in hypo-osmotic solution when HA cervical content is high at the end of pregnancy. In summary, it is critical to account for swelling deformation mechanisms after excision in mechanical experiments. STATEMENT OF SIGNIFICANCE: The cervical extracellular matrix (ECM) undergoes drastic changes to fulfill the functional change of the cervix during pregnancy. Inappropriate timing for this transformation can result in preterm birth, a severe clinical challenge. One of the fundamental changes of the cervical ECM is the significant modification of the glycosaminoglycan content, especially hyaluronan (HA), which is thought to contribute significantly to the swelling and mechanical properties of the cervix. This study aims to measure the swelling kinetics of cervical tissue during pregnancy and to investigate the role of HA in these swelling tendencies. Results show the significant swelling of cervical tissue, which evolves as pregnancy progresses, highlighting a key material property feature of the remodeled cervix. Using a mouse strain with a cervical HA depletion, this work shows HA contributes to the swelling trends of late-term cervical tissue, in a hypo-osmotic solution., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Spectrally selective fat saturation (FatSat) sequence is commonly used to suppress signal from adipose tissue. Conventional SINC-shaped pulses are sensitive to B 0 off-resonance and B 1 + offset. Uniform fat saturation with large spatial coverage is especially challenging for the body and breast MRI. The aim of this study is to develop spectrally selective FatSat pulses that offer more immunity to B 0 /B 1 + field inhomogeneities than SINC pulses and evaluate them in bilateral breast imaging at 3 T., Materials and Methods: Optimized composite pulses (OCP) were designed based on the optimal control theory with robustness to a targeted B 0 / B 1 + conditions. OCP pulses also allows flexible flip angles to meet different requirements. Comparisons with the vendor-provided SINC pulses were conducted by numerical simulation and in vivo scans using a 3D T 1 -weighted (T 1 w) gradient-echo (GRE) sequence with coverage of the whole-breast., Results: Simulation revealed that OCP pulses yielded almost half of the transition band and much less sensitivity to B 1 + inhomogeneity compared to SINC pulses with B 0 off-resonance within ±200 Hz and B 1 + scale error within ±0.3 (P < 0.001). Across five normal subjects, OCP FatSat pulses produced 25-41% lower residual fat signals (P < 0.05) with 27-36% less spatial variation (P < 0.05) than SINC., Conclusion: In contrast to conventional SINC-shaped pulses, the newly designed OCP FatSat pulses mitigated challenges of wide range of B 0 / B 1 + field inhomogeneities and achieved more uniform fat suppression in bilateral breast T 1 w imaging at 3 T., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: A BI-RADS 3 assessment on breast MRI is given when a finding is estimated to have less than 2% chance of breast cancer. Patients in this category are typically recommended to return for a 6-month follow-up MRI. Compliance with this recommendation is low, and we aim to understand which factors are associated with compliance., Materials and Methods: All patients with an MRI examination given a BI-RADS category 3 between February 1, 2011, and June 30, 2016, were retrospectively reviewed. Patient demographics and breast-related medical history were extracted from the electronic medical record. Patients presenting for follow-up MRI between 3 and 10 months were considered compliant. Univariate and multivariate analysis was performed to identify which patient-level factors were associated with compliance with follow-up MRI., Results: Overall, 190 women with a BI-RADS 3 assessment on MRI were included in the study. Of these women, 106 were compliant with the recommended follow-up MRI (57.3%), 34 had delayed follow-up (18.4%), and 45 were noncompliant (24.3%). Reason for examination, personal history of breast cancer, and family history of breast cancer were significantly associated with compliance., Conclusions: We found that 75.7% of patients had a follow-up MRI after a BI-RADS 3 assessment, but only 57.3% were timely in their follow-up. Our data suggest that there may be subsets of patients who would benefit from additional support and resources to help increase overall compliance and timely compliance., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare the sociodemographic characteristics of participants in a contraceptive initiative by housing security and determine the association between housing insecurity on contraceptive method selection before and after the removal of cost., Study Design: This cross-sectional assessment includes 4,327 reproductive-aged participants in the HER Salt Lake Contraceptive Initiative who sought new contraceptive services and reported housing status at enrollment. HER Salt Lake prospectively explored the impact of improved contraceptive access on socioeconomic outcomes in Salt Lake County (USA). For six months (September 2015-March 2016) we collected control data, which included clinic standard-of-care cost-sharing. The intervention started March 2016, and provided no-cost contraception services and unlimited opportunities for method switching over the subsequent three years., Results: There were 964 (22%) housing-insecure participants. Compared to those with stable housing, housing-insecure individuals more commonly identified as a sexual minority, received public assistance and lacked health insurance. Housing-insecure women preferentially selected long-acting reversible contraception during the control period (aOR 1.60; 95%CI 1.01-2.56), but method selection equalized across housing status during the intervention., Conclusions: When cost is not a barrier, all women desire a comprehensive selection of contraceptive methods, regardless of housing security. Contraceptive clients in this vulnerable population need interventions which address access barriers to all methods to support reproductive planning., Implications: Unintended pregnancy during housing insecurity may result in homelessness. This study found housing-insecure women desire access to all contraceptive methods, not just long acting reversible contraception. Integration of comprehensive family planning initiatives into efforts to address homelessness is essential to support this vulnerable population in their reproductive planning., (Published by Elsevier Inc.)

Purpose: The aim of the study was to determine if men who report avoiding adolescent fatherhood through a partner's use of abortion have different socioeconomic outcomes than men who report a live birth during adolescence., Methods: We analyzed a subsample of men who reported a pregnancy before the age of 20 years that ended in either a live birth (n = 460) or abortion (n = 137) in the National Longitudinal Study of Adolescent to Adult Health. We used propensity score and exact matching of baseline characteristics from Wave I of the study completed in 1994 to compare college completion and income reported in Wave IV of the study completed between 2007 and 2008., Results: Among men who reported a live birth, 5.8% reported graduating from college, and 32.4% had any post-high school education compared with 22.1%, and 58.5% of men who reported a pregnancy ended in abortion. In the multivariable matching analysis, men whose adolescent pregnancies ended in abortion had an increased probability of graduating from college (average treatment effect = 8.6; p < .01) and completing any post-high school education in the treatment group (average treatment effect of the treated = 16.5; p < .001) than men whose adolescent pregnancies ended in live birth. We found a positive association between abortion and personal income only compared to men who did not reside with their child born during adolescence., Conclusion: Women's use of abortion services were associated with educational benefits for men who report teen pregnancies., (Copyright © 2019 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Achieving excellent outcomes for patients with congenital heart disease requires coordinated effort and resources, and a need has developed for a structure that facilitates improvement and measures cardiac centers' progress toward optimal patient care., Methods: The Heart Institute (HI) at Cincinnati Children's Hospital developed a Safety, Quality and Value (SQV) program to formalize the use of quality improvement (QI) methods with the goal of optimizing patient outcomes, experience, and value. The SQV program adopted a conceptual framework that considers aspects of structure, process, outcome, and value in defining quality metrics, and the program used the Model for Improvement to guide design and implementation of QI interventions., Results: In the first four years since its inception, the SQV program facilitated important improvements in clinical outcomes, cost reductions, and safety. In addition to achieving measurable improvements, the creation of a formal SQV program fostered a culture of transparency and accountability, providing a new structure for how the HI shares clinical data among clinicians, hospital leadership, and the public., Conclusion: The creation of an infrastructure to strategically design, implement, and support QI efforts in a clinically busy pediatric acquired and congenital heart institute was successful in meeting its initial aims and is a promising approach and model for other programs., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nearly half of women will switch or discontinue using their selected contraceptive method in the first year. Research on early switching or discontinuation provides important clinical and public health insights, although few studies have assessed associated factors, particularly among longitudinal cohorts., Objective: The current study explores attributes associated with early contraceptive method switching or discontinuation (<6 months of initiation) among participants enrolled in the intervention cohorts of the Highly Effective Reversible Contraceptive Initiative Salt Lake Contraceptive Initiative (Utah, United States)., Materials and Methods: Highly Effective Reversible Contraceptive Initiative Salt Lake participants have access to no-cost contraception for 3 years. This includes both the initial selection and the ability to switch or to discontinue methods without cost. Methods available included the following: nonhormonal behavioral methods (male/female condoms, withdrawal, diaphragms, cervical caps, and fertility awareness); short-acting methods (pill, patch, ring, and injectable); and long-acting methods (intrauterine devices and contraceptive implants). Participants completed surveys at baseline and at 1, 3, and 6 months. We collected data on participant demographics, contraceptive continuation, switching, and discontinuation, as well as factors associated with these changes, including established measures of pregnancy intention and ambivalence and reasons for switching or discontinuing. We conducted descriptive statistics, univariable, and multivariable Poisson regression analyses to assess predictors of both discontinuation and switching. We also conducted χ 2 analyses to compare reported reasons for stopping between switchers and discontinuers., Results: At 6 months, 2,583 women (70.0%) reported continuation of their baseline method, 367 (10%) reported at least 1 period of discontinuation, 459 (12.4%) reported switching to a different method, and 279 (7.6%) did not provide 6-month follow-up. Factors associated with discontinuation included selection of a short-acting method (incidence rate ratio [IRR], 2.49; 95% confidence interval [CI], 1.97, 3.12), report of Hispanic ethnicity (IRR, 1.45; 95% CI, 1.12, 1.89) and nonwhite race (IRR, 1.48; 95% CI, 1.08, 2.02), and having any future pregnancy plans, even years out. Participants with some college education were less likely to report discontinuation (IRR, 0.73; 95% CI, 0.57, 0.94). Selecting a short-acting method at baseline was also associated with increased likelihood of method switching (IRR, 2.29, 95% CI, 1.87, 2.80), as was having 2 or more children (IRR, 1.37; 95% CI, 1.08, 1.74). Women were less likely to switch if they were on their parents' insurance (IRR, 0.74; 95% CI, 0.56, 0.99). Among participants who switched methods, 36.9% switched to a long-acting reversible method, 31.7% switched to a short-acting hormonal method, and 31.1% switched to a nonhormonal behavioral method, such as condom use. Of participants providing a reason for stopping, 454 women (73.2%) reported side effects as 1 reason for switching or discontinuing their initial method., Conclusion: Early contraceptive method switching and discontinuation are frequent outcomes of contraceptive use. These changes are common even with removal of contraceptive access barriers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To explore women's responses to PATH questions (Pregnancy Attitudes, Timing and How important is pregnancy prevention) about hypothetical pregnancies and associations with contraceptive method selection among individuals who present as new contraceptive clients and desire to prevent pregnancy for at least 1 year., Study Design: The HER Salt Lake Contraceptive Initiative provided no-cost contraception to new contraceptive clients for 1 year at family planning health centers in Salt Lake County. Those who wanted to avoid pregnancy for at least 1 year and completed the enrollment survey are included in the current study. We used Poisson regression to explore the association between survey-adapted PATH questions and contraceptive method selection., Results: Based on an analytic sample of 3121 individuals, we found pregnancy timing and happiness about hypothetical pregnancies to be associated with method selection. Clients who report plans to wait more than 5 years [prevalence rate (PR) 1.14; 95% confidence interval (CI) 1.05-1.24], those who never wanted to become pregnant (PR 1.16; 95% CI 1.07-1.26) or those who were uncertain (PR=1.19; 95% CI 1.09-1.30) were all more likely to select IUDs and implants than women who reported wanting to become pregnant within 5 years. Greater happiness was associated with lower chance of choosing an IUD or implant (PR 0.98; 95% CI 0.96-0.999). Expressed importance of pregnancy prevention was not significantly associated with any specific contraceptive choice., Conclusions: Pregnancy intentions and happiness about a hypothetical pregnancy were independently associated with selection of IUDs and implants., Implications: Pregnancy attitudes, plans and emotions inform clients' contraceptive needs and behaviors. Client-centered contraceptive care may benefit from a more nuanced PATH approach rather than relying on a single time-oriented question about pregnancy intention., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To estimate the prevalence of sexual-minority women among clients in family planning centers and explore differences in LARC uptake by both sexual identity (i.e., exclusively heterosexual, mostly heterosexual, bisexual, lesbian) and sexual behavior in the past 12 months (i.e., only male partners, both male and female partners, only female partners, no partners) among those enrolled in the survey arm of the HER Salt Lake Contraceptive Initiative., Methods: This survey categorized participants into groups based on reports of sexual identity and sexual behavior. We report contraceptive uptake by these factors, and we used logistic and multinomial logistic models to assess differences in contraceptive method selection by sexual identity and behavior., Results: Among 3901 survey respondents, 32% (n=1230) identified with a sexual-minority identity and 6% had had a female partner in the past 12 months. By identity, bisexual and mostly heterosexual women selected an IUD or implant more frequently than exclusively heterosexual women and demonstrated a preference for the copper T380 IUD. Exclusively heterosexual and lesbian women did not differ in their contraceptive method selection, however, by behavior, women with only female partners selected IUDs or implants less frequently than those with only male partners., Conclusion: One in three women attending family planning centers for contraception identified as a sexual minority. Sexual-minority women selected IUDs or implants more frequently than exclusively heterosexual women., Implications: Providers should avoid care assumptions based upon sexual identity. Sexual-minority women should be offered all methods of contraception and be provided with inclusive contraceptive counseling conversations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Spontaneous preterm birth (SPTB), defined as delivery before 37 weeks' gestation, remains a significant obstetric dilemma even after decades of research in this field. Although trends from 2007 to 2014 showed the rate of preterm birth slightly decreased, the CDC recently reported the rate of preterm birth has increased for two consecutive years since 2014. Currently, 1 in 10 pregnancies in the US still end prematurely. In this chapter, we focus on the "compartment" of the cervix. The goal is to outline the current knowledge of normal cervical structure and function in pregnancy and the current knowledge of how the cervix malfunctions lead to SPTB. We review the mechanisms by which our current interventions are hypothesized to work. Finally, we outline gaps in knowledge and future research directions that may lead to novel and effective interventions to prevent premature cervical failure and SPTB., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A well-timed modification of both the collagen and elastic fiber network in the cervix during pregnancy accompanies the evolution of tissue mechanical parameters that are key to a successful pregnancy. Understanding of the cervical mechanical behaviour along normal and abnormal pregnancy is crucial to define the molecular events that regulate remodeling in term and preterm birth (PTB). In this study, we measured the mechanical response of mouse cervical tissue to a history of cyclic loading and quantified the tissue's ability to recover from small and large deformations. Assessments were made in nonpregnant, pregnant (gestation days 6, 12, 15 and 18) and mouse models of infection mediated PTB treated with lipopolysaccharide on gestation d15 (LPS treated) and hormone withdrawal mediated PTB on gestation d15 (RU486 treated). The current study uncovers the contributions of collagen and elastic fiber networks to the progressive change in mechanical function of the cervix through pregnancy. Premature cervical remodeling induced on gestation day 15 in the LPS infection model is characterized by distinct mechanical properties that are similar but not identical to mechanical properties at term ripening on day 18. Remodeling in the LPS infection model results in a weaker cervix, unable to withstand high loads. In contrast, the RU486 preterm model resembles the cyclic mechanical behaviour seen for term d18 cervix, where the extremely compliant tissue is able to withstand multiple cycles under large deformations without breaking. The distinct material responses to load-unload cycles in the two PTB models matches the differing microstructural changes in collagen and elastic fibers in these two models of preterm birth. Improved understanding of the impact of microstructural changes to mechanical performance of the cervix will provide insights to aid in the development of therapies for prevention of preterm birth., Statement of Significance: Preterm Birth (PTB) still represents a serious challenge to be overcome, considering its implications on infant mortality and lifelong health consequences. While the causes and etiologies of PTB are diverse and yet to be fully elucidated, a common pathway leading to a preterm delivery is premature cervical remodeling. Throughout pregnancy, the cervix remodels through changes of its microstructure, thus altering its mechanical properties. An appropriate timing for these transformations is critical for a healthy pregnancy and avoidance of PTB. Hence, this study aims at understanding how the mechanical function of the cervix evolves during a normal and preterm pregnancy. By performing cyclic mechanical testing on cervix samples from animal models, we assess the cervix's ability to recover from moderate and severe loading. The developed methodology links mechanical parameters to specific microstructural components. This work identifies a distinct biomechanical signature associated with inflammation mediated PTB that differs from PTB induced by hormone withdrawal and from normal term remodeling., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence., Patients and Methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers., Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21)., Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab., Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Background: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma., Patients and Methods: We carried out droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial., Results: Mutant BRAF or NRAS ctDNA was detected (≥1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval [DFI; hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.79-5.47; P < 0.0001] and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80-5.79; P < 0.0001) versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status and disease stage (DFI: HR 3.26, 95% CI 1.83-5.83, P < 0.0001; DMFI: HR 3.45, 95% CI 1.88-6.34, P < 0.0001). Five-year overall survival rate for patients with detectable ctDNA was 33% (95% CI 14%-55%) versus 65% (95% CI 56%-72%) for those with undetectable ctDNA. Overall survival was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.40-4.96); P = 0.003) and remained significant after adjustment for performance status (HR 2.50, 95% CI 1.32-4.74, P = 0.005)., Conclusion: ctDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy., Clinical Trial Number: ISRCTN 81261306., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosomal fragility, progressive marrow failure, and cancer predisposition. Hematopoietic cell transplantation (HCT) is curative for FA-related marrow failure or leukemia, but both radiation exposure during transplant and graft-versus-host disease (GVHD) may increase risk of later malignancies of the head and neck and anogenital area. In this study, we tested a radiation-free conditioning regimen with a T-cell-depleted graft to eliminate radiation exposure and minimize early and late toxicities of transplant. Forty-five patients (median age, 8.2 years; range 4.3-44) with FA underwent HCT between June 2009 and May 2014. The preparative regimen included busulfan, cyclophosphamide, fludarabine, and rabbit anti-thymocyte globulin. Busulfan levels were monitored to avoid excess toxicity. All grafts were CD34-selected/T-cell-depleted using the CliniMacs CD34 columns (Miltenyi). Thirty-four patients (75.6%) with marrow failure and 11 (24.4%) with myelodysplastic syndrome underwent HCT using matched unrelated (n = 25, 55.5%), mismatched unrelated (n = 14, 31.1%), or mismatched related donors (n = 6, 13.4%). One year probabilities of overall and disease-free survival for the entire cohort, including patients with myeloid malignancy and those receiving mismatched related/haploidentical grafts, were 80% (±6%) and 77.7% (±6.2%), respectively (median follow-up 41 months). All young children (<10 years of age) undergoing HCT for marrow failure using low-dose busulfan-containing regimen survived. No patients developed acute grade 3-4 GVHD. Sequential reduction of busulfan dose was successfully achieved per study design. Our results show excellent outcomes in patients with FA undergoing alternative donor HCT without radiation exposure. The study is registered to www.clinicaltrials.gov as #NCT01082133., (© 2017 by The American Society of Hematology.)

Industrial hog operations (IHOs) have been identified as a source of antibiotic-resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). However, few studies have investigated the presence of antibiotic-resistant S. aureus in the environment near IHOs, specifically surface waters proximal to spray fields where IHO liquid lagoon waste is sprayed. Surface water samples (n=179) were collected over the course of approximately one year from nine locations in southeastern North Carolina and analyzed for the presence of presumptive MRSA using CHROMagar MRSA media. Culture-based, biochemical, and molecular tests, as well as matrix-assisted laser desorption/ionization-time of flight mass spectrometry were used to confirm that isolates that grew on CHROMagar MRSA media were S. aureus. Confirmed S. aureus isolates were then tested for susceptibility to 16 antibiotics and screened for molecular markers of MRSA (mecA, mecC) and livestock adaptation (absence of scn). A total of 12 confirmed MRSA were detected in 9 distinct water samples. Nine of 12 MRSA isolates were also multidrug-resistant (MDRSA [i.e., resistant to ≥3 antibiotic classes]). All MRSA were scn-positive and most (11/12) belonged to a staphylococcal protein A (spa) type t008, which is commonly associated with humans. Additionally, 12 confirmed S. aureus that were methicillin-susceptible (MSSA) were recovered, 7 of which belonged to spa type t021 and were scn-negative (a marker of livestock-adaptation). This study demonstrated the presence of MSSA, MRSA, and MDRSA in surface waters adjacent to IHO lagoon waste spray fields in southeastern North Carolina. To our knowledge, this is the first report of waterborne S. aureus from surface waters proximal to IHOs., (Copyright © 2016. Published by Elsevier B.V.)

Unlabelled: An appropriately timed cervical remodeling process is critical for a healthy delivery, yet little is known about the material property changes of the cervix in pregnancy because obtaining human tissue samples is difficult. Rodent models offer advantages including accurately timed pregnant tissues and genetically altered models. Determining the material properties of the mouse cervix, however, is challenging because of its small size and complex geometry. The aim of this study is to quantify cervical material property changes in a normal mouse pregnancy using a microstructurally-inspired porous fiber composite model. We mechanically test intact, whole, gestation-timed mouse cervix by pulling apart tensioned sutures through its inner canal. To interpret our mechanical testing results, we conduct an inverse finite element analysis, taking into account the combined loading state of the thick-walled cylindrical tissue. We fit the material model to previous osmotic swelling data and load-deformation data from this study using a nonlinear optimization scheme, and validate the model by predicting a separate set of deformation data. Overall, the proposed porous fiber composite model captures the mechanical behavior of the mouse cervix in large deformation. The evolution of cervical material parameters indicates that in a normal mouse pregnancy, the cervix begins to soften between day 6 and day 12 of a 19-day gestation period. The material parameter associated with the collagen fiber stiffness decreases from 3.4MPa at gestation day 6 to 9.7e-4MPa at gestation day 18, while the ground substance stiffness decreases from 2.6e-1MPa to 7.0e-4MPa., Statement of Significance: Accelerated cervical remodeling can lead to extremely premature births. Little is known, however, about the material property changes of the cervix in pregnancy because pregnant human tissue samples are limited. Rodent models overcome this limitation and provide access to gestation-timed samples. Measuring the material property changes of the mouse cervix in pregnancy is challenging due to its small size and complex geometry. Here, we establish a combined experimental and modeling framework. We use this framework to determine the cervical material property changes throughout a normal mouse pregnancy. We present our experimental methods for mechanically testing whole, intact cervical tissue samples. We fit a porous fiber composite material model to the mechanical data and show that the mouse cervix begins to soften between day 6 and day 12 of a 19-day gestation period., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To test the effectiveness of a telehealth service delivery model for the treatment of children with attention-deficit/hyperactivity disorder (ADHD) that provided pharmacological treatment and caregiver behavior training., Method: The Children's ADHD Telemental Health Treatment Study (CATTS) was a randomized controlled trial with 223 children referred by 88 primary care providers (PCPs) in 7 communities. Children randomized to the experimental telehealth service model received 6 sessions over 22 weeks of combined pharmacotherapy, delivered by child psychiatrists through videoconferencing, and caregiver behavior training, provided in person by community therapists who were supervised remotely. Children randomized to the control service delivery model received treatment with their PCPs augmented with a telepsychiatry consultation. Outcomes were diagnostic criteria for ADHD and oppositional defiant disorder (ODD) and role performance on the Vanderbilt ADHD Rating Scale (VADRS) completed by caregivers (VADRS-Caregivers) and teachers (VADRS-Teachers) and impairment on the Columbia Impairment Scale-Parent Version (CIS-P). Measures were completed at 5 assessments over 25 weeks., Results: Children in both service models improved. Children assigned to the telehealth service model improved significantly more than children in the augmented primary care arm for VADRS-Caregiver criteria for inattention (χ(2)[4] = 19.47, p < .001), hyperactivity (χ(2)[4] = 11.91, p = .02), combined ADHD (χ(2)[4] = 14.90, p = .005), ODD (χ(2)[4] = 10.05, p = .04), and VADRS-Caregiver role performance (χ(2) [4] = 12.40, p = .01) and CIS-P impairment (χ(2)[4] = 20.52, p < .001). For the VADRS-Teacher diagnostic criteria, children in the telehealth service model had significantly more improvement in hyperactivity (χ(2)[4] = 11.28, p = .02) and combined ADHD (χ(2)[4] = 9.72, p = .045)., Conclusion: The CATTS trial demonstrated the effectiveness of a telehealth service model to treat ADHD in communities with limited access to specialty mental health services. Clinical trial registration information-Children's Attention Deficit Disorder With Hyperactivity (ADHD) Telemental Health Treatment Study; http://clinicaltrials.gov; NCT00830700., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Swine farming has gone through many changes in the last few decades, resulting in operations with a high animal density known as confined animal feeding operations (CAFOs). These operations produce a large quantity of fecal waste whose environmental impacts are not well understood. The purpose of this study was to investigate microbial water quality in surface waters proximal to swine CAFOs including microbial source tracking of fecal microbes specific to swine. For one year, surface water samples at up- and downstream sites proximal to swine CAFO lagoon waste land application sites were tested for fecal indicator bacteria (fecal coliforms, Escherichia coli and Enterococcus) and candidate swine-specific microbial source-tracking (MST) markers (Bacteroidales Pig-1-Bac, Pig-2-Bac, and Pig-Bac-2, and methanogen P23-2). Testing of 187 samples showed high fecal indicator bacteria concentrations at both up- and downstream sites. Overall, 40%, 23%, and 61% of samples exceeded state and federal recreational water quality guidelines for fecal coliforms, E. coli, and Enterococcus, respectively. Pig-1-Bac and Pig-2-Bac showed the highest specificity to swine fecal wastes and were 2.47 (95% confidence interval [CI]=1.03, 5.94) and 2.30 times (95% CI=0.90, 5.88) as prevalent proximal down- than proximal upstream of swine CAFOs, respectively. Pig-1-Bac and Pig-2-Bac were also 2.87 (95% CI=1.21, 6.80) and 3.36 (95% CI=1.34, 8.41) times as prevalent when 48 hour antecedent rainfall was greater than versus less than the mean, respectively. Results suggest diffuse and overall poor sanitary quality of surface waters where swine CAFO density is high. Pig-1-Bac and Pig-2-Bac are useful for tracking off-site conveyance of swine fecal wastes into surface waters proximal to and downstream of swine CAFOs and during rain events., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Photodynamic therapy (PDT) is an established cancer treatment. Molecular-targeted agents targeting phosphatidylinositol 3-kinase (PI3K) pathway is showing great promise as anticancer drugs. This study compared SVEC mouse endothelial and PC-3 human prostate tumor cells in the response to verteporfin-mediated photodynamic therapy (PDT) and a pan-PI3K pathway inhibitor LY294002., Methods: Verteporfin cellular uptake and intracellular localization was determined by spectrofluorometry and confocal fluorescence microscopy, respectively, in the SVEC and PC-3 cells. Cytotoxicity induced by LY294002 and verteporfin-PDT was assessed by the MTS assay. Effects of treatments on cell survival and death signaling were examined by Western blot analysis., Results: PC-3 cells had a higher cellular uptake of verteporfin than SVEC cells at 15min after incubation with verteporfin. Verteporfin was mainly localized in mitochondria in both SVEC and PC-3 cells. Verteporfin-PDT alone as well as PDT in combination with LY294002 induced more apoptosis and caused more reduction in cell viability in SVEC cells than in PC-3 cells. PC-3 cells exhibited a higher level of anti-apoptotic Bcl-2 family proteins than SVEC cells., Conclusions: SVEC cells were more responsive to verteporfin-PDT and PI3K pathway inhibitor LY294002 than PC-3 cells. Such differences in response were likely due to differences in Bcl-2 family protein level. These results support tumor vascular targeting by verteporfin-PDT and its therapeutic enhancement by PI3K pathway inhibition., (Copyright © 2015 Elsevier B.V. All rights reserved.)

North Carolina is the second leading state in pork production in the United States, with over 10 million swine. Swine manure in NC is typically collected and stored in open-pit lagoons before the liquid waste is sprayed onto agricultural fields for disposal. Components of this waste may be able to impact surface water quality with the potential for human exposure. This study examined viruses of public health concern in creeks adjacent to swine concentrated animal feeding operation (CAFO) spray fields. Surface water samples (n=154) were collected from public access waters in proximity to swine CAFO spray fields for six months and were tested for hepatitis E virus (HEV) and coliphages. HEV was detected in one sample. Somatic coliphages were detected in 98% of samples (geometric mean 24 ± 4.1 PFU per 100 ml), and F+ coliphages were detected in 85% of samples (geometric mean 6.8 ± 5.0 PFU per 100 ml). Only 3% (21) of the F+ coliphage isolates were RNA phage, and all of the F+ RNA coliphages belonged to genogroup I. Although the pervasiveness of swine CAFOs in this area prevented a comparison with samples from un-impacted sites, the near ubiquity of coliphages, as well as the presence of HEV, suggests that current waste management practices may be associated with the dissemination of viruses of public health concern in waters proximal to CAFO spray fields., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Transplant-associated thrombotic microangiopathy (TMA) leads to generalized endothelial dysfunction that can progress to multiorgan injury, and severe cases are associated with poor outcomes after hematopoietic stem cell transplantation (HSCT). Identifying patients at highest risk for severe disease is challenging. We prospectively evaluated 100 consecutive HSCT recipients to determine the incidence of moderate and severe TMA and factors associated with poor overall outcomes. Thirty-nine subjects (39%) met previously published criteria for TMA. Subjects with TMA had a significantly higher nonrelapse mortality (43.6% vs 7.8%, P < .0001) at 1 year post-HSCT compared with those without TMA. Elevated lactate dehydrogenase, proteinuria on routine urinalysis, and hypertension were the earliest markers of TMA. Proteinuria (>30 mg/dL) and evidence of terminal complement activation (elevated sC5b-9) in the blood at the time of TMA diagnosis were associated with very poor survival (<20% at 1 year), whereas all TMA subjects without proteinuria and a normal sC5b-9 serum concentration survived (P < .01). Based on these prospective observations, we conclude that severe TMA occurred in 18% of HSCT recipients in our cohort and propose an algorithm to identify the highest-risk patients who might benefit from prompt clinical interventions., (© 2014 by The American Society of Hematology.)

Growth and remodeling of biological tissues involves mass exchanges between soluble building blocks in the tissue's interstitial fluid and the various constituents of cells and the extracellular matrix. As the content of these various constituents evolves with growth, associated material properties, such as the elastic modulus of the extracellular matrix, may similarly evolve. Therefore, growth theories may be formulated by accounting for the evolution of tissue composition over time in response to various biological and mechanical triggers. This approach has been the foundation of classical bone remodeling theories that successfully describe Wolff's law by establishing a dependence between Young's modulus and bone apparent density and by formulating a constitutive relation between bone mass supply and the state of strain. The goal of this study is to demonstrate that adding tissue composition as state variables in the constitutive relations governing the stress-strain response and the mass supply represents a very general and straightforward method to model interstitial growth and remodeling in a wide variety of biological tissues. The foundation for this approach is rooted in the framework of mixture theory, which models the tissue as a mixture of multiple solid and fluid constituents. A further generalization is to allow each solid constituent in a constrained solid mixture to have its own reference (stress-free) configuration. Several illustrations are provided, ranging from bone remodeling to cartilage tissue engineering and cervical remodeling during pregnancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: There are few reports of pediatric studies of atrial fibrillation (AF). We sought to describe the clinical characteristics, management strategies, and recurrence rates and to identify predictors of AF recurrence in a contemporary pediatric population., Methods: A retrospective review was performed of patients ≤ 18 years with lone AF who were seen at 4 pediatric institutions from 1996-2011. Patients with AF in the setting of thyroid disease, ventricular pre-excitation, coexisting congenital heart disease, or a history of cardiac surgery were excluded. Demographics, clinical presentation, investigations, treatment, and follow-up were analyzed., Results: Forty-two patients were diagnosed with a first episode of lone AF, and 4 of these cases were later classified as persistent AF. Thirty-one (74%) were male patients, median age was 15.3 years, and median (interquartile range [IQR]) duration of AF episode was 12 (IQR, 7-24) hours. AF recurred in 39% (15 of 38) of patients. The Kaplan-Meier median time to estimated recurrence was 19 months. By univariate analysis, initial AF episode duration was associated with a higher risk of recurrence (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1-1.02; P = 0.034). Sex, age, family history, size of the left atrium, and history of cardioversion were not associated with recurrence. Recurrence with another supraventricular tachyarrhythmia (SVT) was observed in 6 of 38 (16%) patients, and 12 patients underwent electrophysiology (EP) study, with 6 patients receiving ablation., Conclusions: Our reported rate of recurrence of 39% is important when counseling pediatric patients and their parents on the expected course and treatment goals., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to determine the effect the source of added nitrite and high hydrostatic pressure (HHP) had on the growth of Listeria monocytogenes on ready-to-eat (RTE) sliced ham. Use of 600MPa HHP for 3min resulted in an immediate 3.9-4.3log CFU/g reduction in L. monocytogenes numbers, while use of 400MPa HHP (3min) provided less than 1log CFU/g reduction. With the 600MPa HHP treatment, sliced ham with a conventional concentration of sodium nitrite (200ppm) was not different in L. monocytogenes growth from use with 50 or 100ppm of sodium nitrite in pre-converted celery powder. Instrumental color values as well as residual nitrite and residual nitrate concentrations for cured (sodium nitrite and nitrite from celery powder) and uncured ham formulations are discussed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Growth of Listeria monocytogenes was evaluated for up to 182 days after inoculation on ready-to-eat (RTE) sliced ham and turkey breast formulated with sodium nitrite (0 or 200 ppm), sodium chloride (1.8% or 2.4%), and treated (no treatment or 600 MPa) with high hydrostatic pressure (HHP). HHP at 600 MPa for 3 min resulted in a 3.85-4.35 log CFU/g reduction in L. monocytogenes. With formulations at similar proximate analyses, one of the evaluation days (day 21) without HHP showed significantly greater growth of L. monocytogenes in ham than in turkey breast, but there were no significant differences on other evaluation days or with HHP. There were no differences in growth of L. monocytogenes due to sodium chloride level. Sodium nitrite provided a small, but significant inhibition of L. monocytogenes without HHP, but addition of sodium nitrite did not significantly affect growth of L. monocytogenes with use of HHP., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Over the past 10years there has been ongoing development of curing processes with natural ingredients designed to meet consumer demand and regulatory requirements for natural and organic processed meats. Initially, these processes utilized celery concentrates with a high nitrate content combined with a nitrate-reducing starter culture. Subsequent advances included celery concentrates with the nitrate converted to nitrite by suppliers. Further, as questions developed concerning reduced concentration of preservatives and the microbiological safety of these processed meats, additional advances have resulted in a wide variety of ingredients and processes designed to provide supplementary antimicrobial effects for improved product safety., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: This study sought to examine the changes in ventricular function of hypoplastic left heart syndrome (HLHS) between the first 2 stages of surgical palliation., Background: The mortality risk between first and second stages of surgical palliation in HLHS remains high. Right ventricular (RV) dysfunction predicts mortality. Postulated mechanisms include a maladaptive contraction pattern, myocardial ischemia, or contraction asynchrony. Speckle tracking imaging allows accurate measurement of myocardial deformation without geometric assumptions., Methods: Prospective echocardiography pre-Norwood and pre-bidirectional cavopulmonary anastomosis (BCPA) examinations were performed in 20 HLHS patients, with comparisons made between stages. Measurements of ventricular function included: longitudinal/circumferential strain ratio, reflecting changes in contraction pattern; post-systolic strain index, a potential marker of myocardial ischemia; and mechanical dyssynchrony index. Relationships between echocardiographic variables and magnetic resonance imaging RV parameters before BCPA were examined., Results: Before BCPA, myocardial contractility estimated by isovolumic acceleration and strain rate was reduced, paralleled by an increased in post-systolic strain index (p < 0.01). Right ventricular longitudinal/circumferential strain ratio decreased, becoming similar to a left ventricle-like contraction pattern, and this correlated with decreased mechanical dyssynchrony index (r = 0.65, p < 0.01), magnetic resonance imaging RV end-diastolic volume (r = 0.65, p < 0.05) and mass (r = 0.71, p < 0.01). Ventricular strain (r = -0.72, p < 0.01), strain rate (r = -0.85, p < 0.001), and mechanical dyssynchrony index (r = -0.73, p < 0.01) correlated linearly with magnetic resonance imaging-derived RV ejection fraction., Conclusions: Reduced RV contractility occurred before BCPA. RV with a left ventricle-like contraction pattern was associated with improved contraction synchrony as well as a reduction in RV size and mass in HLHS. The finding of increased post-systolic strain index before BCPA is novel and its potential link with myocardial ischemia warrants further investigation. RV strain, strain rate, and contraction synchrony measured by speckle tracking imaging correlated closely with ventricular function and might be useful for monitoring ventricular function in HLHS., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Accurate DNA replication is essential to genome integrity and is controlled by five human RecQ helicases, of which at least three prevent cancer and ageing. Here, we have studied the role of RECQL5, which is the least characterised of the five human RecQ helicases. We demonstrate that overexpressed RECQL5 promotes survival during thymidine-induced slowing of replication forks in human cells. The RECQL5 protein relocates specifically to stalled replication forks and suppresses thymidine-induced RPA foci, CHK1 signalling, homologous recombination and gammaH2AX activation. It is unlikely that RECQL5 promotes survival through translesion synthesis as PCNA ubiquitylation is also reduced. Interestingly, we also found that overexpressing RECQL5 relieves cells of the cell cycle arrest normally imposed by thymidine, but without causing mutations. In conclusion, we propose that RECQL5 stabilises the replication fork allowing replication to overcome the effects of thymidine and complete the cell cycle., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Objective: To assess the efficacy of endovenous laser therapy (EVLT) for treating saphenous reflux associated with varicose veins., Design: Out-patient treatment by EVLT with an 810nm laser wavelength with results assessed by ultrasound surveillance., Patients: 361 patients who received EVLT for 509 incompetent saphenous veins over a five-year period., Methods: EVLT was used for proximal saphenous veins and ultrasound-guided sclerotherapy (UGS) for distal saphenous veins and tributaries. Control of reflux and occlusion or obliteration of the saphenous veins was assessed by serial ultrasound studies. Univariate Kaplan-Meier life table analysis showed cumulative primary and secondary success rates, and multivariate Cox regression analysis assessed covariates that could be associated with increased risk of ultrasound failure., Results: Life table analysis showed primary success at four years in 76% (95% CI 56-87%) and secondary success at four years after further treatment of recurrence by UGS in 97% (95% CI 93-99%). Cox regression analysis showed a non-significant trend towards worse primary success in male patients and worse results for older patients and limbs with clinical CEAP categories C4-6. Cox regression showed significantly worse secondary success for limbs with clinical CEAP C4-6., Conclusions: EVLT effectively controls saphenous reflux particularly with ultrasound surveillance to detect early recurrence that can be treated by UGS. Modifications in technique may be required to improve the late primary success rate.

This practice parameter discusses the use of telepsychiatry to provide services to children and adolescents. The parameter defines terms and reviews the status of telepsychiatry as a mode of health service delivery. Because many of the issues addressed are unique to telepsychiatry, the parameter presents principles for establishing a telepsychiatry service and optimizing clinical practice within that service. The principles presented are based on existing scientific evidence and clinical consensus. Telepsychiatry is still evolving, and this parameter represents a first approach to determining "best practices." The parameter emphasizes the integration of telepsychiatry within other practice parameters of the American Academy of Child and Adolescent Psychiatry.

Objective: To determine which covariates predisposed to deep venous occlusion (DVO) after ultrasound-guided sclerotherapy (UGS) for varicose veins., Design: Ultrasound scans before and at 3 to 7 days after UGS to detect post-procedure deep venous occlusion., Materials: A consecutive series of 1931 treatment sessions in 852 patients treated by a technique for UGS., Methods: Ultrasound examination of the full length of axial deep veins above and below knee before and soon after every procedure. Crude chi(2) analysis of all covariates allowed selection of those that showed apparent significant influence. Logistic regression analysis of these then determined which independently predisposed to post-procedure deep venous occlusion., Results: Deep venous occlusion was only observed after UGS using foamed sclerosant and occurred following 28 treatment sessions. No significant difference for risk of deep venous occlusion was observed for patient characteristics or which veins were treated. Logistic regression analysis showed significant independent increased risk in a limb from using highly diluted or undiluted sclerosant (OR 0.55; 95% CI 0.19 to 1.59 for 0.6-1.0% solution, OR 10.45; 95% CI 3.12 to 34.99 for 2-2.3% and OR 0.36; 95% CI 0.07 to 1.74 for 3% solution), treating veins >or=5mm diameter (OR 3.70; 95% CI 1.23 to 11.13) and injecting >or=10 ml of foamed sclerosant for a limb (OR 3.64; 95% CI 1.21 to 10.90)., Conclusions: The risk of deep venous occlusion after UGS in this series was lower when using highly diluted or undiluted sclerosant, when treating veins less than 5mm in diameter and when restricting the volume of foam injected to less than 10 ml.

The mechanical integrity of cervical tissue is crucial for maintaining a healthy gestation. Altered tissue biochemistry can cause drastic changes in the mechanical properties of the cervix and contribute to premature cervical dilation and delivery. We present an investigation of the mechanical and biochemical properties of cervical samples from human hysterectomy specimens. Three clinical cases were investigated: nonpregnant hysterectomy patients with previous vaginal deliveries; nonpregnant hysterectomy patients with no previous vaginal deliveries; and pregnant hysterectomy patients at time of cesarean section. Tissue samples were tested in confined compression, unconfined compression and tension. Cervical tissue samples for the three clinical cases were also subjected to biochemical analysis. Biochemical assays measured cervical tissue hydration, collagen content, collagen extractability and sulfated glycosaminoglycan (GAG) content. Results from the mechanical tests indicate that cervical stroma has a nonlinear, time-dependent stress response with varying degrees of conditioning and hysteresis depending on its obstetric background. It was found that the nonpregnant tissue was significantly stiffer than the pregnant tissue in both tension and compression. Further, collagen extractability, sulfated GAG content and hydration were substantially higher in the pregnant tissue. This study is the first important step towards the attainment of an improved understanding of the complex interplay between the molecular structure of cervical tissue and its macroscopic mechanical properties.