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The etiology of testicular germ cell tumors (TGCTs) is poorly understood, with cryptorchidism and family history being the only well-established risk factors. Body size, age at puberty, and dairy consumption, however, have been suggested to be related to TGCTs. To clarify the relation of these variables to TGCT risk and to one another, the authors analyzed data from 767 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study (2002-2005). Overall, increased height was significantly related to risk (odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.36, 2.45), though body mass index was not (OR = 1.06, 95% CI: 0.66, 1.69). There was no association with age at puberty, based on ages at first shaving (OR = 1.29, 95% CI: 0.96, 1.73), voice changing (OR = 0.97, 95% CI: 0.71, 1.32), and nocturnal emissions (OR = 1.00, 95% CI: 0.73, 1.37). Similarly, there was no relation with dairy consumption at any age between birth and 12th grade. These results suggest that height is a risk factor for TGCTs, but the relation is unlikely explained by childhood dairy consumption. As adult height is largely determined in the first 2 years of life, increased attention to events in this interval may help elucidate the etiology of TGCTs. [ABSTRACT FROM AUTHOR]

Objective: Sexual function among testicular cancer survivors is a concern because affected men are of reproductive age when diagnosed. We conducted a case-control study among United States military men to examine whether testicular cancer survivors experienced impaired sexual function.Methods: A total of 246 testicular cancer cases and 236 ethnicity and age matched controls were enrolled in the study in 2008-2009. The Brief Male Sexual Function Inventory (BMSFI) was used to assess sexual function.Results: Compared to controls, cases scored significantly lower on sex drive (5.77 vs. 5.18), erection (9.40 vs. 8.63), ejaculation (10.83 vs. 9.90), and problem assessment (10.55 vs. 9.54). Cases were significantly more likely to have impaired erection (OR 1.72; 95% CI 1.11-2.64), ejaculation (OR 2.27; 95% CI 1.32-3.91), and problem assessment (OR 2.36; 95% CI 1.43-3.90). In histology and treatment analysis, nonseminoma, chemotherapy and radiation treated cases risk of erectile dysfunction, delayed ejaculation, and/or problem assessment were greater when compared to controls.Conclusion: This study provides evidence that testicular cancer survivors are more likely to have impaired sexual functioning compared to demographically matched controls. The observed impaired sexual functioning appeared to vary by treatment regimen and histologic subtype. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence of testicular germ cell tumors among active duty males and compare it with the incidence in the general U.S. population.Methods: The Automated Cancer Tumor Registry and the Surveillance, Epidemiology, and End Results Program data from 1990 to 2003 were analyzed for men aged between 20 and 59 years by histology and stage at diagnosis. Rates were age adjusted using the male active duty military population as the standard.Results: Nonseminoma incidence was significantly lower in the military than in the general population (incidence rate ratio = 0.90, 95% confidence interval = 0.82-0.98). Trends in incidence tended to be similar in both the populations. Increases were observed for both histologic types but were only significant for seminoma (Automated Cancer Tumor Registry: 21% and Surveillance, Epidemiology, and End Results program: 16%; p < 0.05). Increases in incidence were only observed for localized tumors of both histologic types.Conclusions: The lower incidence of nonseminoma in the military and the increased incidence of localized tumors in both populations remain unexplained. [ABSTRACT FROM AUTHOR]

Solid organ transplantation (SOT) is considered the optimal treatment for children with end-stage organ failure; however, increased efforts are needed to understand the gap surrounding equitable access to and health outcomes of SOT for Indigenous children. This scoping review summarizes the literature on the characteristics of access to and health outcomes of pediatric SOT among Indigenous children in the settler-colonial states of Canada, Aotearoa New Zealand, Australia, and the United States. A search was performed on MEDLINE, EMBASE, PsycINFO, and CINAHL for studies matching preestablished eligibility criteria from inception to November 2021. A preliminary gray literature search was also conducted. Twenty-four studies published between 1996 and 2021 were included. Studies addressed Indigenous pediatric populations within the United States (n = 7), Canada (n = 6), Aotearoa New Zealand (n = 5), Australia (n = 5), and Aotearoa New Zealand and Australia combined (n = 1). Findings showed that Indigenous children experienced longer time on dialysis, lower rates of preemptive and living donor kidney transplantation, and disparities in patient and graft outcomes after kidney transplantation. There were mixed findings about access to liver transplantation for Indigenous children and comparable findings for graft and patient outcomes after liver transplantation. Social determinants of health, such as geographic remoteness, lack of living donors, and traditional spiritual beliefs, may affect SOT access and outcomes for Indigenous children. Evidence gaps emphasize the need for action-based initiatives within SOT that prioritize research with and for Indigenous pediatric populations. Future research should include community-engaged methodologies, situated within local community contexts, to inform culturally safe care for Indigenous children., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: There is a disparity in the availability of health care for children in resource-constrained countries. The International Pediatric Nephrology Association (IPNA) commissioned an initiative exploring the challenges in the care of children with kidney disease in low- or middle-income countries (LMICs) with a focus on human, diagnostic, and therapeutic resources., Methods: A survey was sent by e-mail to all members of IPNA and its affiliated regional or national societies residing in LMICs. Data were extracted from individual responses after merging duplicate data. Descriptive analysis was done using Microsoft Excel., Results: Responses were obtained from 245 centers across 62 countries representing 88% of the LMIC pediatric population. Regional disparity in the availability of basic diagnostic and therapeutic resources was noted. Even when resources were available, they were not accessible or affordable in 15% to 20% of centers. Acute and chronic dialysis were available in 85% and 75% of centers respectively. Lack of trained nurses, pediatric-specific supplies, and high costs were barriers to providing dialysis in these regions. Kidney transplantation was available in 32% of centers, with the cost of transplantation and lack of surgical expertise reported as barriers. About 65% of centers reported that families with chronic disease opted to discontinue care, with financial burden as the most common reason cited., Conclusion: The survey highlights the existing gaps in workforce, diagnostic, and therapeutic resources for pediatric kidney care in resource-constrained regions. We need to strengthen the health care workforce, address disparities in health care resources and funding, and advocate for equitable access to medications, and kidney replacement therapy (KRT)., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Objectives: Because congenital anomalies of the kidneys and urinary tract (CAKUT) represent a frequent cause of end stage renal disease (ESRD) in the young, we explored the epidemiology of CAKUT and the role of diabetes in pregnancy., Methods: This was a retrospective cohort study of CAKUT, by maternal diabetes status, from among all 1980‒2009 births in Saskatchewan First Nations (FN) and non-First Nations (non-FN) people. We determined frequencies, predictors and complications of CAKUT, as well as cumulative survival (to 2014) of affected persons until ESRD and death., Results: Of the 411,055 babies (204,167 mothers) in the Saskatchewan maternal-infant database, 2,540 had CAKUT (391 FN and 2,149 non-FN). Overall annual CAKUT incidence was 0.63% for non-FN and 0.57% for FN (p=0.082), but 5-year CAKUT incidence only increased among FN (0.40% in 1980‒1984 and 0.76% in 2005‒2009, p<0.0001) and was highest among offspring of FN mothers with pregestational diabetes (pre-G/DM) (0% before 1995, 2.51% in 2000‒2004 and 1.66% in 2005-2009). Pre-G/DM, but not gestational diabetes mellitus (GDM), was an independent predictor of CAKUT in non-FN (odds ratio, 1.79; 95% confidence interval, 1.20 to 2.69), and in FN interacting with maternal history of stillbirth (odds ratio, 7.90; 95% confidence interval, 1.14 to 54.6). ESRD was >100-fold more likely among offspring with CAKUT compared with all other offspring and was responsible for 40% of ESRD cases in young FN and non-FN people., Conclusions: In Saskatchewan, pre-G/DM is an emerging cause of CAKUT, accounting for 40% of ESRD cases in FN/non-FN children and young adults. Because pre-G/DM‒related CAKUT is potentially preventable with optimal glycemic management, increased recognition of this serious complication is required., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to compare the depth of cure (DOC) of a resin-based composite (RBC) using the ISO DOC protocol with stainless-steel and molar-tooth molds (4 mm cylindrical cavity). The tooth mold included testing with and without the occlusal surface being covered with black tape around the cavity opening. The RBC was cured with either halogen (HAL) or light-emitting diode (LED) light. The results showed that specimens made in the non-taped tooth mold had DOCs that were significantly greater (28%-35%) than those in the stainless-steel mold. The taped tooth mold also produced significantly greater DOCs, but only by 6%-8%. Knoop hardness (KNH) measurements along the central axis of the RBC specimens showed that depths for 80% of maximum hardness were substantially greater than those determined by the ISO DOC protocol but were limited to the center and quickly dropped below 80% in a lateral direction. The KHN mapping for each of the three molds found that the ISO DOCs could validate a KHN of ≥80% across the RBC to the periphery, only for the non-taped tooth mold. This was due to light incident on the tooth surrounding the RBC being scattered into the RBC., (© 2019 Eur J Oral Sci.)

Objective: The aim of this study was to observe the resin/dentin interfaces of universal adhesives by using scanning electron microscopy (SEM), and to compare their morphologies with conventional etch & rinse (ER) and self-etch (SE) adhesive systems., Methods: Two three-step and one two-step ER adhesives and two two-step and two single-step SE adhesives were used for comparison with seven universal adhesives in ER mode and SE mode, respectively. Bonded surfaces with bovine teeth were longitudinally sectioned and mirror-polished. Half of the samples were treated with HCl and NaOCl solutions. The interfaces were subjected to argon ion beam etching and then observed by scanning electron microscopy., Results: The thickness of the adhesive layer (AL) of most of the seven universal adhesives and single-step SE adhesives was similar. Universal adhesives in SE mode formed a hybrid smear layer as a high-density zone between the AL and dentin. The thickness of the hybrid layer (HL) of the universal adhesives in ER mode was ∼1-2μm, with a high-density zone (reaction layer [RL]) below the HL., Conclusion: The morphological features of most universal adhesives in SE mode and single-step SE adhesives are similar. Although resin-dentin interfaces of universal adhesives in ER mode resemble those of ER adhesives, universal adhesives have a distinctive feature, an RL., Significance: The RL might be a sign of chemical bonding even when using universal adhesives in ER mode., (Copyright © 2019 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Since its recent reformulation, alfaxalone has gained popularity as an injectable veterinary anesthetic, including promising studies demonstrating the use of alfaxalone-xylazine for anesthesia in mice. Here we sought to expand these studies by testing additional dose ranges, elaborating on physiologic monitoring, testing sex- and strain-associated differences, and evaluating efficacy during actual surgical conditions. C57BL/6J mice showed significant sex-associated differences in anesthetic sensitivity, with males requiring higher doses of alfaxalone (80-120 mg/kg IP alfaxalone with 10 mg/kg IP xylazine) than females (40-80 mg/kg IP alfaxalone with 10 mg/kg IP xylazine) to achieve a surgical plane of anesthesia. In addition, female outbred CD1 mice were less sensitive to alfaxalone than female inbred C57BL/6J mice. When used during actual surgery, alfaxalone-xylazine administered intraperitoneally provided adequate anesthesia for a model of orthopedic surgery, whereas the same anesthetic regimen during laparotomy resulted in unacceptably high mortality; survival during laparotomy increased when drugs were administered subcutaneously. These results indicate that alfaxalone-xylazine may be a viable option for injectable surgical anesthesia in mice, although strain- and sex-associated differences and alternative routes of administration should be considered when optimizing the anesthetic regimen for specific experimental conditions.

A new annelid species within the Prionospio- complex (Spionidae), Laubieriellus cacatua sp. nov., is described from material collected from the continental slope off the western margin of Australia. Laubieriellus cacatua sp. nov. is distinguished by having dorsal crests from chaetigers 6 to 11 and ventral crests on chaetigers 2 to 11. Neuropodial hooded hooks are present from chaetiger 10, with 2 pairs of apical teeth above the main tooth. Ventral sabre chaetae are present from chaetiger 10. This is the first record of Laubieriellus in Australia.

The purpose of this study was to examine the shear fatigue strengths of a resin composite bonded to dentin. Three adhesive systems - a two-step self-etch adhesive (OptiBond XTR; Kerr) and two universal adhesives [Scotchbond Universal (3M ESPE) and G-Premio Bond (GC)] - were used in self-etch mode to bond a resin composite to dentin at a physiologic frequency of 2 Hz over 50,000, 100,000, and 1,000,000 cycles. A staircase method of fatigue testing was used. Twenty specimens were used for each test condition. There was no significant difference in shear fatigue strength across the cycling periods for the three individual adhesives. Differences in shear fatigue strength were found among the three adhesives within each cycling period. Regardless of the adhesive used in self-etch mode for bonding a resin composite to dentin, shear fatigue strength was not influenced by the number of cycles used for testing., (© 2018 Eur J Oral Sci.)

Objective: The purpose of this study was to determine the influence of different smear layers on enamel and dentin bond durability of various types of self-etch adhesives., Methods: Two universal adhesives, Scotchbond Universal (SU) and Prime & Bond elect (PE); a conventional single-step self-etch adhesive, G-ænial Bond (GB); and two two-step self-etch adhesives, Optibond XTR (OX) and Clearfil SE Bond (SE) were used in this study. Shear bond strengths (SBS) and shear fatigue strengths (SFS) to human enamel and dentin were determined with different smear layer conditions. The prepared specimens were divided into three groups. The bonding surfaces were prepared by grinding with either (1) #180, (2) #600, or (3) #4000-SiC papers before making the bonded assemblies. For each group, 15 specimens were prepared for the SBS and 30 specimens for the SFS., Results: The two-step self-etch adhesives showed significantly higher SFS values than the single-step self-etch adhesives, regardless of the smear layer condition or substrate. Although most of the tested adhesives showed no significant differences in enamel SFS values among the smear layer groups, SU, GB, and SE showed significantly lower SFS values in the #180 in dentin groups than the #600 and #4000 groups., Conclusion: The influence of different smear layer conditions on bond durability was adhesive dependent. Furthermore, the smear layers generated on different substrates also influenced the bond quality of the self-etch adhesives., Significance: Smear layer conditions of enamel and dentin influence the bond durability of universal adhesives and conventional single and two-step self-etch adhesives., (Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

The influence of the number of cycles on shear fatigue strength to enamel and dentin using dental adhesives in self-etch mode was investigated. A two-step self-etch adhesive and two universal adhesives were used to bond to enamel and dentin in self-etch mode. Initial shear bond strength and shear fatigue strength to enamel and dentin using the adhesive in self-etch mode were determined. Fatigue testing was used with 20 Hz frequency and cycling periods of 50,000, 100,000 and 1,000,000 cycles, or until failure occurred. For each of the cycling periods, there was no significant difference in shear fatigue strength across the cycling periods for the individual adhesives. Differences in shear fatigue strength were found between the adhesives within the cycling periods. Regardless of the adhesive used in self-etch mode for bonding to enamel or dentin, shear fatigue strength was not influenced by the number of cycles used for shear fatigue strength testing.

Objectives: The aim of this study was to determine the effect of double-layer application of universal adhesives on the bond quality and compare to other adhesive systems., Methods: Two universal adhesives used were in this study: Scotchbond Universal (SU), [3M ESPE] and Prime & Bond elect (PE), [Dentsply Caulk]. The conventional single-step self-etch adhesives G-ӕnial Bond (GB), [GC Corporation.] and BeautiBond (BB), [Shofu Inc.], and a two-step self-etch adhesive, Optibond XTR (OX), [Kerr Corporation], were used as comparison adhesives. Shear bond strengths (SBS) and shear fatigue strengths (SFS) to human enamel and dentin were measured in single application mode and double application mode. For each test condition, 15 specimens were prepared for SBS testing and 30 specimens for SFS testing., Results: Enamel and dentin SBS of the universal adhesives in the double application mode were significantly higher than those of the single application mode. In addition, the universal adhesives in the double application mode had significantly higher dentin SFS values than those of the single application mode. The two-step self-etch adhesive OX tended to have lower bond strengths in the double application mode, regardless of the test method or adherent substrate., Conclusion: The double application mode is effective in enhancing SBS and SFS of universal adhesives, but not conventional two-step self-etch adhesives., Significance: These results suggest that, although the double application mode may enhance the bonding quality of a universal adhesive, it may be counter-productive for two-step self-etch adhesives in clinical use., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In diabetes, glucocorticoid secretion increases secondary to hyperglycemia and is associated with an extensive list of disease complications. Levels of cortisol in humans, or corticosterone in rodents, are usually measured as transitory biomarkers of stress in blood or saliva. Glucocorticoid concentrations accumulate in human or animal hair over weeks and could more accurately measure the cumulative stress burden of diseases like chronic diabetes. In this study, corticosterone levels were measured in hair in verified rodent models of diabetes mellitus. To induce type 1 diabetes, C57BL/6J mice were injected with streptozotocin and blood and hair samples were collected 28days following induction. Leptin receptor deficient (db/db) mice were used as a spontaneous model of type 2 diabetes and blood and hair samples were collected at 8weeks of age, after the development of hyperglycemia and obesity. Corticosterone levels from serum, new growth hair and total growth hair were analyzed using an enzyme immunoassay. Corticosterone levels in new growth hair and serum were significantly elevated in both models of diabetes compared to controls. In contrast, corticosterone levels in old hair growth did not differ significantly between diabetic and non-diabetic animals. Thus, hair removal and sampling of new hair growth was a more sensitive procedure for detecting changes in hair corticosterone levels induced by periods of hyperglycemia lasting for 4weeks in mice. These results validate the use of hair to measure long-term changes in corticosterone induced by diabetes in rodent models. Further studies are now needed to validate the utility of hair cortisol as a tool for measuring the stress burden of individuals with diabetes and for following the effects of long-term medical treatments., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain. The goal of these studies was to determine whether the MOR-mediated behavioral effects of BPN were altered in the Oprm1 A112G mouse model of the human OPRM1 A118G SNP. All studies were conducted in female, AA, AG and GG mice. BPN's maximal analgesic effect in the hot plate test was significantly blunted in AG and GG mice compared to wild type AA mice. Similarly, the BPN-induced reduction of latency to consume food in the novelty induced hypophagia test was blocked entirely in AG and GG mice compared to their AA littermates. In addition, GG mice exhibited marked reductions in psychostimulant hyperlocomotor activity compared to the AA group. In contrast, reduced immobility in the forced swim test, an effect of BPN mediated by kappa opioid receptors, was not affected by genotype. These studies demonstrate the ability of the Oprm1 A112G SNP to attenuate the analgesic, anxiolytic and hyperlocomotor effects of BPN. Overall, these data suggest that the OPRM1 A118G SNP will significantly impact the clinical efficacy of BPN in its therapeutic applications., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Buprenorphine (BPN), a mixed opioid drug with high affinity for mu (MOR) and kappa (KOR) opioid receptors, has been shown to produce behavioral responses in rodents that are similar to those of antidepressant and anxiolytic drugs. Although recent studies have identified KORs as a primary mediator of BPN's effects in rodent models of depressive-like behavior, the role of MORs in BPN's behavioral effects has not been as well explored. The current studies investigated the role of MORs in mediating conditioned approach behavior in the novelty-induced hypophagia (NIH) test, a behavioral measure previously shown to be sensitive to chronic treatment with antidepressant drugs. The effects of BPN were evaluated in the NIH test 24h post-administration in mice with genetic deletion of the MOR (Oprm1 -/- ) or KOR (Oprk1 -/- ), or after pharmacological blockade with the non-selective opioid receptor antagonist naltrexone and selective MOR antagonist cyprodime. We found that behavioral responses to BPN in the NIH test were blocked in Oprm1 -/- mice, but not in Oprk1 -/- mice. Both cyprodime and naltrexone significantly reduced approach latency at doses experimentally proven to antagonize the MOR. In contrast the selective MOR agonist morphine and the selective KOR antagonist nor-BNI were both ineffective. Moreover, antinociceptive studies revealed persistence of the MOR antagonist properties of BPN at 24h post-administration, the period of behavioral reactivity. These data support modulation of MOR activity as a key component of BPN's antidepressant-like effects in the NIH paradigm., (Copyright © 2016. Published by Elsevier B.V.)

Background: Data guiding the timing of dialysis initiation in children are limited. We sought to determine current practice and secular trends in Canada with respect to the timing of dialysis initiation in children based on estimated glomerular filtration rate (eGFR)., Methods: This observational study included incident chronic dialysis patients aged ≤21 years identified from the Canadian Organ Replacement Register who started dialysis in Canada between January 2001 and December 2010 at any of the nine participating Canadian centers (n = 583). Youth were categorized utilizing CKiD Schwartz eGFR into ≥10.5 (higher) or <10.5 ml/min/1.73 m 2 (lower) eGFR groups. Differences at dialysis initiation by facility and region were examined, and secular trends were determined., Results: Median eGFR at dialysis initiation was 8.1 (interquartile range 5.4-11.0) ml/min/1.73 m 2 . Overall, 29 % of the patients started dialysis with an eGFR of ≥10.5 ml/min/1.73 m 2 . The proportion of children starting with higher eGFR increased from 27.3 % in 2001 to 35.4 % in 2010 (p = 0.04) and differed by treatment facility (12-70 %; p = 0.0001). Factors associated with higher eGFR at dialysis initiation in the adjusted regression model were female sex [odds ratio (OR) 1.48; 95 % confidence interval (CI) 1.02-2.14], genetic cause of end-stage kidney disease (OR 2.77; 95 % CI 1.37-5.58) and living ≥50 km from treatment facility (OR 1.47; 95 % CI 1.01-2.14)., Conclusions: One-third of the children were found to have initiated dialysis with an eGFR ≥10.5 ml/min/1.73 m 2 , however significant practice variation exists with respect to timing of dialysis initiation by treatment facility. More data is required to evaluate the clinical implications of this practice variation.

The purpose of this study was to examine the effect of mold diameter on depth of cure of a resin-based composite material for varying amounts of irradiation. A resin-based composite was light-cured for 10-80 s in stainless-steel molds of either 6 mm or 4 mm in diameter and then dark-stored for 24 h. Specimens were then scraped back and the length of the cured specimens was measured to provide depth of cure (D SB ). Radiant exposure to each of the mold diameters was determined by measuring the power. The D SB values using the 4-mm molds were lower than those of the 6-mm molds. The average difference between the two groups for each irradiation time was 0.45 ± 0.02 mm. A fixed depth of cure required about 39% more irradiation time for the 4-mm mold than for the 6-mm mold but 75% more radiant exposure. The difference in cure depth for a fixed radiant exposure was 0.79 mm. A better comparison of depth of cure is obtained by using identical radiant exposures for different mold diameters. It is believed that greater loss of light by absorption at the stainless-steel cylinder walls for the 4-mm-diameter cylinders accounts for the lower depth of cure when compared with the 6-mm molds., (© 2017 Eur J Oral Sci.)

Objectives: The purpose of this study was to determine the influence of different frequency rates on of bond durability of self-etch adhesives to enamel using shear fatigue strength (SFS) testing., Methods: A two-step self-etch adhesive (OX, OptiBond XTR), and two single step self-etch adhesives (GB, G-ӕnial Bond and SU, Scotchbond Universal) were used in this study. The shear fatigue strength (SFS) to enamel was obtained. A staircase method was used to determine the SFS values with 50,000 cycles or until failure occurred. Fatigue testing was performed at frequencies of 5Hz, 10Hz, and 20Hz. For each test condition, 30 specimens were prepared for the SFS testing., Results: Regardless of the bond strength test method, OX showed significantly higher SFS values than the two single-step self-etch adhesives. For each of the three individual self-etch adhesives, there was no significant difference in SFS depending on the frequency rate, although 20Hz results tended to be higher., Conclusions: Regardless of the self-etch adhesive system, frequencies of 5Hz, 10Hz, and 20Hz produced similar results in fatigue strength of resin composite bonded to enamel using 50,000 cycles or until bond failure., Significance: Accelerated fatigue testing provides valuable information regarding the long term durability of resin composite to enamel bonding using self-etch adhesive system., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Significant practice variation exists in Canada with respect to timing of dialysis initiation in children. In the absence of evidence to guide practice, physicians' perceptions may significantly influence decision-making., Objective: The objectives of this study are to (1) evaluate Canadian pediatric nephrologists' perceptions regarding dialysis initiation in children with chronic kidney disease (CKD) and (2) determine the factors guiding practice that may contribute to practice variation across Canada., Design: This study was a cross-sectional online survey., Setting: This study was done in academic pediatric nephrology centers in Canada., Participants: The participants of this study are pediatric nephrologists., Measurements and Methods: An anonymous web-based survey was administered to pediatric nephrologists in Canada to evaluate perspectives and practice patterns regarding timing of dialysis initiation. We also explored the importance of estimated glomerular filtration rate (eGFR) vs. symptoms and the role of patient and provider factors influencing decisions., Results: Thirty-five nephrologists (59 %) completed the survey. Most respondents care for advanced CKD patients in a multidisciplinary clinic (86 %) and no centers have a formal policy on timing of dialysis initiation. Seventy-five percent of centers follow <20 stage 4-5 CKD patients, and 9 % follow >30 patients. Discussions about dialysis initiation are generally informal (75 %) and the decision to start is made by the nephrologist (37 %) or a team (57 %). Fifty percent agreed GFR was important when deciding when to initiate dialysis, 41 % were neutral, and 9 % disagreed. Variability exists in the threshold that nephrologists considered early (vs. late) dialysis initiation: >20 (21 %), >15 (38 %), >12 (26 %), and >10 ml/min/1.73 m(2) (12 %). Practitioners however typically start dialysis in asymptomatic patients at eGFRs of 7-9 (9 %), 10-11 (41 %), 12-14 (38 %), and 15-19 (6 %) ml/min/1.73 m(2). Patient factors important in the decision to start dialysis for >90 % of nephrologists were fatigue, >10 % weight loss, nausea, increasing missed school, and awaiting a pre-emptive transplant. Age was only a factor for 56 %., Limitations: This study has a 59 % response rate., Conclusions: Variability exists in Canada regarding the importance and threshold of eGFR guiding the decision as to when to start dialysis in children, whereas patient symptoms are almost universally important to pediatric nephrologists' decision-making. Additional studies evaluating outcomes of children starting dialysis earlier vs. later are needed to standardize decision-making and care for children with kidney failure.

Damage to long white matter pathways in the cerebral cortex is known to affect memory capacity. However, the specific contribution of interhemispheric connectivity in memory functioning is only beginning to become understood. The present study examined verbal and visual memory processing in individuals with agenesis of the corpus callosum (AgCC) using the Wechsler Memory Scale-Third Edition (WMS-III; Wechsler, 1997b). Thirty participants with AgCC (FSIQ >78) were compared against 30 healthy age and IQ matched controls on auditory/verbal (Logical Memory, Verbal Paired Associates) and visual (Visual Reproduction, Faces) memory subtests. Performance was worse in AgCC than controls on immediate and delayed verbal recall for rote word pairs and on delayed recall of faces, as well as on percent recall for these tasks. Immediate recall for thematic information from stories was also worse in AgCC, but groups did not differ on memory for details from narratives or on recall for thematic information following a time delay. Groups also did not differ on memory for abstract figures or immediate recall of faces. On all subtests, individuals with AgCC had greater frequency of clinically significant impairments than predicted by the normal distribution. Results suggest less efficient overall verbal and visual learning and memory with relative weaknesses processing verbal pairs and delayed recall for faces. These findings suggest that the corpus callosum facilitates more efficient learning and recall for both verbal and visual information, that individuals with AgCC may benefit from receiving verbal information within semantic context, and that known deficits in facial processing in individuals with AgCC may contribute to their impairments in recall for faces., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The purpose of this study was to use shear bond strength (SBS) and shear fatigue strength (SFS) testing to determine the influence on dentin bonding of phosphoric acid pre-etching times before the application of self-etch adhesives. Two single-step self-etch universal adhesives [Prime & Bond Elect (EL) and Scotchbond Universal (SU)], a conventional single-step self-etch adhesive [G-aenial Bond (GB)], and a two-step self-etch adhesive [OptiBond XTR (OX)] were used. The SBS and SFS values were obtained with phosphoric acid pre-etching times of 3, 10, or 15 s before application of the adhesives, and for a control without pre-etching. For groups with 3 s of pre-etching, SU and EL showed higher SBS values than control groups. No significant difference was observed for GB among the 3 s, 10 s, and control groups, but the 15 s pre-etching group showed significantly lower SBS and SFS values than the control group. No significant difference was found for OX among the pre-etching groups. Reducing phosphoric acid pre-etching time can minimize the adverse effect on dentin bonding durability for the conventional self-etch adhesives. Furthermore, a short phosphoric acid pre-etching time enhances the dentin bonding performance of universal adhesives., (© 2016 Eur J Oral Sci.)

The present study aimed to determine the effect of the functional monomer, 10-methacryloxydecyl dihydrogen phosphate (MDP), on the enamel bond durability of single-step self-etch adhesives through integrating fatigue testing and long-term water storage. An MDP-containing self-etch adhesive, Clearfil Bond SE ONE (SE), and an experimental adhesive, MDP-free (MF), which comprised the same ingredients as SE apart from MDP, were used. Shear bond strength (SBS) and shear fatigue strength (SFS) were measured with or without phosphoric acid pre-etching. The specimens were stored in distilled water for 24 h, 6 months, or 1 yr. Although similar SBS and SFS values were obtained for SE with pre-etching and for MF after 24 h of storage in distilled water, SE with pre-etching showed higher SBS and SFS values than MF after storage in water for 6 months or 1 yr. Regardless of the pre-etching procedure, SE showed higher SBS and SFS values after 6 months of storage in distilled water than after 24 h or 1 yr. To conclude, MDP might play an important role in enhancing not only bond strength but also bond durability with respect to repeated subcritical loading after long-term water storage., (© 2015 Eur J Oral Sci.)

Purpose: To examine the effect that a stainless steel (SS) matrix band has on the depth and distribution of cure of a resin-based composite (RBC) in a simulated Class II cavity., Methods: RBC was cured for 20 seconds in a simulated Class II cavity with and without a SS matrix band, and after 24 hours the specimens were scraped back and ground to expose a vertical central plane where Knoop micro-hardness (KHN) mapping was conducted from 0.05-1.5 mm from the band and in 0.5 mm intervals from the top of the specimens. The effect of different angles of the light guide on the distribution of hardness was also examined., Results: KHN values near the SS matrix band were significantly lower (P < 0.05) than within the bulk of the specimen and were lower than those found without the matrix band. Angles of incidence for the curing light-guide produced changes in the distribution of KHN within the specimens, but particularly near the matrix band, and with a 35° angle of incidence, the depth of cure was significantly different from that of normal incidence of the light.

Objectives: The purpose of this study was to determine the dentin bonding ability of three new universal adhesive systems under different etching modes using fatigue testing., Method: Prime & Bond elect [PE] (DENTSPLY Caulk), Scotchbond Universal [SU] (3M ESPE), and All Bond Universal [AU] (Bisco) were used in this study. A conventional single-step self-etch adhesive, Clearfil Bond SE ONE [CS] (Kuraray Noritake Dental) was also included as a control. Shear bond strengths (SBS) and shear fatigue strength (SFS) to human dentin were obtained in the total-etch mode and self-etch modes. For each test condition, 15 specimens were prepared for the SBS and 30 specimens for SFS. SEM was used to examine representative de-bonded specimens, treated dentin surfaces and the resin/dentin interface for each test condition., Results: Among the universal adhesives, PE in total-etch mode showed significantly higher SBS and SFS values than in self-etch mode. SU and AU did not show any significant difference in SBS and SFS between the total-etch mode and self-etch mode. However, the single-step self-etch adhesive CS showed significantly lower SBS and SFS values in the etch-and-rinse mode when compared to the self-etch mode. Examining the ratio of SFS/SBS, for PE and AU, the etch-and-rinse mode groups showed higher ratios than the self-etch mode groups., Significance: The influence of different etching modes on dentin bond quality of universal adhesives was dependent on the adhesive material. However, for the universal adhesives, using the total-etch mode did not have a negative impact on dentin bond quality., (Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Purpose: To use shear bond strength (SBS) and shear fatigue strength (SFS) testing to determine the influence of phosphoric acid pre-etching times prior to application of self-etch adhesives on enamel bonding., Materials and Methods: Two single-step self-etch universal adhesives (Prime&Bond Elect and Scotchbond Universal), a conventional single-step self-etch adhesive (G-ӕnial Bond), and a conventional two-step self-etch adhesive (OptiBond XTR) were used. The SBS and SFS were obtained with phosphoric acid pre-etching for 3, 10, or 15 s prior to application of the adhesives, and without pre-etching (0 s) as a control. A staircase method was used to determine the SFS with 10 Hz frequency for 50,000 cycles or until failure occurred. The mean demineralization depth for each treated enamel surface was also measured using a profilometer., Results: For all the adhesives, the groups with pre-etching showed significantly higher SBS and SFS than groups without pre-etching. However, there was no significant difference in SBS and SFS among groups with > 3 s of preetching. In addition, although the groups with pre-etching showed significantly deeper demineralization depths than groups without pre-etching, there was no significant difference in depth among groups with > 3 s of pre-etching., Conclusion: Three seconds of phosphoric acid pre-etching prior to application of self-etch adhesive can enhance enamel bonding effectiveness.

Intraperitoneal injectable anesthetics are often used to achieve surgical anesthesia in laboratory mice. Because bolus redosing of injectable anesthetics can cause unacceptably high mortality, we evaluated intraperitoneal continuous-rate infusion (CRI) of ketamine with or without xylazine for maintaining surgical anesthesia for an extended period of time. Anesthesia was induced in male C57BL/6J mice by using ketamine (80 mg/kg) and xylazine (8 mg/kg) without or with acepromazine at 0.1 mg/kg or 0.5 mg/kg. At 10 min after induction, CRI for 90 min was initiated and comprised 25%, 50%, or 100% of the initial ketamine dose per hour or 50% of the initial doses of both ketamine and xylazine. Anesthetic regimens were compared on the basis of animal immobility, continuous surgical depth of anesthesia as determined by the absence of a pedal withdrawal reflex, and mortality. Consistent with previous studies, the response to anesthetics was highly variable. Regimens that provided the longest continuous surgical plane of anesthesia with minimal mortality were ketamine-xylazine-acepromazine (0.1 mg/kg) with CRI of 100% of the initial ketamine dose and ketamine-xylazine-acepromazine (0.5 mg/kg) with CRI of 50% of the initial ketamine and xylazine doses. In addition, heart rate and respiratory rate did not increase consistently in response to a noxious stimulus during CRI anesthesia, even when mice exhibited a positive pedal withdrawal reflex, suggesting that these parameters are unreliable indicators of anesthetic depth during ketamine-xylazine anesthesia in mice. We conclude that intraperitoneal CRI anesthesia in mice prolongs injectable anesthesia more consistently and with lower mortality than does bolus redosing.

This study aimed to investigate the effect of frequency on shear fatigue strength (SFS). The SFS of a resin composite bonded to dentin was determined using three self-etch adhesive systems: G-ænial Bond, Scotchbond Universal, and Optibond XTR. The staircase method of fatigue testing was used to determine the SFS at frequencies of 5, 10, and 20 Hz for 50,000 cycles. The failed bonding sites observed were classified based on the type of bond failure as follows: adhesive failure, cohesive failure in composite, cohesive failure in dentin, or mixed failure (partially adhesive, partially cohesive). A modified t-test with Bonferroni correction was used to analyze the SFS data, and a complex chi-square test was used to analyze the fracture modes. The SFS of OX was significantly greater than that of GB at both 5 and 10 Hz. However, no significant differences in SFS were found among the three frequencies (5, 10, and 20 Hz) in the three self-etch adhesive systems. Furthermore, no significant differences in bond failure mode were observed among the three frequency rates in all the three adhesives used.(J Oral Sci 58, 539-546, 2016).

Objectives: The purpose of this study was to determine enamel and dentin bond durability after long-term water storage using self-etch adhesives., Methods: Two single step self-etch adhesives (SU, Scotchbond Universal and GB, G-ӕnial Bond) and a two-step self-etch adhesive (OX, OptiBond XTR) were used. The shear bond strength (SBS) and shear fatigue strength (FS) of the enamel and dentin were obtained with and without phosphoric acid pre-etching prior to application of the adhesives. The specimens were stored in distilled water at 37 °C for 24 h, 6 months, and one year. A staircase method was used to determine the FS using a frequency of 10 Hz for 50,000 cycles or until failure occurred., Results: The SBS and FS of enamel bonds were significantly higher with pre-etching, when compared to no pre-etching for the same water storage period. The FS of dentin bonds with pre-etching tended to decrease relative to no pre-etching at the same storage period. For the one year storage period, SU and GB with pre-etching showed significantly lower FS values than the groups without pre-etching., Conclusions: The influence of water storage on FS of the self-etch adhesives was dependent on the adhesive material, storage period and phosphoric acid pre-etching of the bonding site., Clinical Significance: Phosphoric acid pre-etching of enamel improves the effectiveness of self-etch adhesive systems. Inadvertent contact of phosphoric acid on dentin appears to reduce the ability of self-etch adhesives to effectively bond resin composite materials., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites., Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers., Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures., Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation., (Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

The role of interhemispheric interactions in the encoding, retention, and retrieval of verbal memory can be clarified by assessing individuals with complete or partial agenesis of the corpus callosum (AgCC), but who have normal intelligence. This study assessed verbal learning and memory in AgCC using the California Verbal Learning Test-Second Edition (CVLT-II). Twenty-six individuals with AgCC were compared to 24 matched controls on CVLT-II measures, as well as Donders׳ four CVLT-II factors (i.e., Attention Span, Learning Efficiency, Delayed Memory, and Inaccurate Memory). Individuals with AgCC performed significantly below healthy controls on the Delayed Memory factor, confirmed by significant deficits in short and long delayed free recall and cued recall. They also performed less well in original learning. Deficient performance by individuals with AgCC during learning trials, as well as deficits in all forms of delayed memory, suggest that the corpus callosum facilitates interhemispheric elaboration and encoding of verbal information., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: As the first part of a larger study on curing characteristics of a resin-based composite (RBC), the major objectives were to create an energy-hardness relationship (EHR) that relates Knoop hardness (KHN) with radiant exposure (H), and to do the same for degree of conversion (DC) in the form of an energy-conversion relationship (ECR). Both of these are meant to be universal relationships that satisfy reciprocity between irradiance and time for a given H value., Methods: RBC specimens were made by curing the material in 6mm diameter, stainless steel molds for 10-40s and allowing the material to cure for 24h. Cure depths were determined by a scrape-back method. KHN and DC values were determined along the central axis of the specimens, and these values were related to the internal H values using a measured transmission relationship, T(d), for the RBC., Results: Suitable EHR and ECR relationships were developed for the RBC material that can be used to describe the curing characteristics under various curing conditions. However, predictive accuracy is affected for incident radiant exposures below about 12J/cm(2) to some extent. A relationship between KHN and DC was established., Significance: For the RBC examined, KHN measurements can be used as an alternate method or in conjunction with DC for describing the curing characteristics., (Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to examine the effect different configurations of curing would have on the depth and distribution of the cure within each configuration, for a specific resin-based composite (RBC)., Methods: RBC was cured in a variety of configurations, consisting of 6mm molds of three different colors; large molds that simulated the condition of no mold at all; and 3-6mm diameter molds to check the effect of size. All specimens were cured for 20s with a quartz-halogen lamp and were allowed to cure for 24h in the dark. Transmission measurements were made for these same configurations. Knoop hardness measurements were made across the central plane of some configurations to determine the distribution of curing., Results: Depths of cure and distribution of curing were significantly affected by changes in configuration. Under the configuration of no mold, the cure extended well beyond the periphery of the light guide due to scattering of the light. When a mold was used, a pronounced effect by the walls resulted in decreased hardness as the mold wall was approached, and the severity of this effect was dependent on the color of the mold. It is believed that this is due to absorption/reflection characteristics of light by the walls, with the white molds showing the least effect. Reducing the diameter of the molds resulted in significant decreases in depth of cure, which are attributed to light absorption by the walls that limits the penetration of light during the curing procedure., Significance: Configuration of curing has a significant effect on the depth of cure, but also significantly reduces the cure near the mold wall. This can have clinical ramifications for the cure along a stainless steel matrix band for Class II restorations, and for test procedures in general, where there is no standardization regarding configuration or where measurements are made on specimens., (Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Background: Practice variation is common for nephrotic syndrome (NS) treatment., Methods: A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS., Results: Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4 weeks by 26 %, and 10 % prescribed 'other'. Alternate-day GC was continued for 6 weeks by 63 % of respondents and for >6 and <6 weeks by 32 and 6 %, respectively. For biopsy-confirmed minimal change disease, 65 and 46 % of respondents chose oral cyclophosphamide for frequently relapsing and steroid-dependent phenotypes, respectively; calcineurin inhibitors or mycophenolate were the second most popular choices. Kidney biopsy was 'always' performed by 16, 39, and 97 % of respondents for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Rituximab had been administered by 60 % of respondents; 22, 56, and 72 % reported that they would consider rituximab for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Most notable differences between practice and Guideline recommendations were first presentation GC duration, GC-sparing agent choices in frequently relapsing and steroid-dependent patients, and biopsy practices., Conclusions: There is substantial Canadian practice variation in NS treatment. Assessment of factors driving variation and strategies to implement Guideline recommendations are needed.

Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.

Background: Research on early life exposures and testicular germ cell tumors (TGCT) risk has focused on a possible perinatal etiology with a well-known hypothesis suggesting that hormonal involvement during fetal life is associated with risk. Second-to-fourth digit ratio (2D:4D) and left-hand dominance have been proposed as markers of prenatal hormone exposure., Aim: To evaluate associations between 2D:4D digit ratio, right minus left 2D:4D (ΔR-L), and left-hand dominance and TGCT in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study., Methods: A total of 246 TGCT cases and 236 non-testicular cancer controls participated in the current study, and completed a self-administered questionnaire. Associations between digit ratio, hand dominance and TGCT were estimated using unconditional logistic regression adjusting for identified covariates., Results: Right 2D:4D was not associated with TGCT [odds ratio (OR) for a one-standard deviation (SD) increase in right-hand 2D:4D: 1.12, 95% confidence interval (CI): 0.93-1.34]. The results were consistent when evaluating the association based on the left hand. The difference between right and left-hand 2D:4D was also not associated with TGCT risk [OR for a one-SD increase in ΔR-L: 1.03, 95% CI: 0.87-1.23]. Compared to men who reported right-hand dominance, ambidexterity [OR (95% CI)=0.65 (0.30-1.41)] and left-hand dominance [OR (95% CI)=0.79 (0.44-1.44)] were not associated with risk., Conclusions: These results do not support the hypothesis that prenatal hormonal imbalance is associated with TGCT risk. Given the limited sample size, further evaluation of the relationship between TGCT and prenatal hormonal factors using digit ratio, ΔR-L, or left-hand dominance and larger sample size are warranted., (Published by Elsevier Ireland Ltd.)

We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12-1.26; P = 1.11 × 10(-8)), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14-1.29; P = 5.59 × 10(-9)), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18-1.34; P = 5.15 × 10(-12)) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18-1.33; P = 4.32 × 10(-13) and rs7221274: OR = 1.20, 95% CI = 1.12-1.28; P = 4.04 × 10(-9)), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

Background: Similarities between the age-specific incidence pattern of testicular germ cell tumours (TGCTs) and the age-specific incidence pattern of cancers of viral origin prompted us to evaluate the relationship between common infections occurring during childhood or young adult life and TGCT using existing data from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study., Methods: TGCT cases diagnosed between 2002 and 2005 (n=767) were matched on age, race and serum draw date to at least one control (n=929)., Results: None of the infections evaluated were associated with TGCT risk. Further, a meta-analysis of mumps and mumps orchitis or orchitis infection did not support an association with TGCT (mumps pooled odds ratio (OR): 1.03, 95% confidence interval (CI): 0.89-1.20; mumps orchitis or orchitis pooled OR: 1.80, 95% CI: 0.74-4.42)., Conclusion: Based on our evaluation of childhood and early life infections and meta-analyses of mumps and mumps orchitis and/or orchitis, TGCT does not appear to be associated with common childhood infections.