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With the current development of the 5G infrastructure, there presents a unique opportunity for the deployment of battery-less mmWave reflect-array-based sensors. These fully-passive devices benefit from having a larger detectability than alternative battery-less solutions to create self-monitoring megastructures. The presented 'smart' skin sensor uses a Van-Atta array design enabling ubiquitous local strain monitoring for the structural health monitoring of composite materials featuring wide interrogation angles. Proof-of-concept prototypes of these 'smart' skin millimeter-wave identification tags, that can be mounted on or embedded within common materials used in wind turbine blades, present a highly-detectable radar cross-section of − 33.75 dBsm and − 35.00 dBsm for mounted and embedded sensors respectively. Both sensors display a minimum resolution of 202 μ -strain even at 40 ∘ off-axis enabling interrogation of the fully-passive sensor at oblique angles of incidence. When interrogated from a proof-of-concept reader, the fully-passive, sticker-like mmID enables local strain monitoring of both carbon fiber and glass fiber composite materials. The sensors display a repeatable and recoverable response over 0–3000 μ -strain and a sensitivity of 7.55 kHz/ μ -strain and 7.92 kHz/ μ -strain for mounted and embedded sensors, respectively. Thus, the presented 5G-enabled battery-less sensor presents massive potential for the development of ubiquitous Digital Twinning of composite materials in future smart cities architectures. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic cancer (PC) in solid organ transplant (SOT) recipients is not well studied. Some PC cases may be incidentally detected during hepatobiliary imaging. Methods: We evaluated PC among 374,106 SOT recipients during 1995–2017 in the United States using linked data from the national transplant registry and multiple state/regional cancer registries. Standardized incidence ratios (SIRs) were used to compare PC risk in recipients to the general population. We used multivariate Poisson regression to identify independent risk factors for PC. We assessed survival after PC diagnosis using Kaplan–Meier curves and log-rank tests. Results: SOT recipients had elevated incidence for PC compared with the general population (SIR 1.40, 95% CI 1.29–1.52), and this increase was strongest in liver recipients (1.65, 1.41–1.92). Among all recipients, PC incidence was especially increased for cases arising in the head of the pancreas (SIR 1.50, 95% CI 1.34–1.68) and for cases diagnosed at localized stage (1.85, 1.37–2.44). Among SOT recipients, factors independently associated with increased incidence were consistent with those in general population including male sex, older age, non-O blood type, and history of diabetes. Additionally, compared to other organ recipients, liver transplant recipients had higher PC incidence (adjusted incidence rate ratio 1.28; 95% CI 1.06–1.54). Overall survival after PC diagnosis was poor (median 4 months) and similar between liver and other organ transplant recipients (p = 0.08). Conclusions: PC incidence is elevated among SOT recipients, and more commonly diagnosed in liver transplant recipients perhaps related to incidental detection. However, survival is poor even in liver recipients, arguing against routine PC screening. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) protocols increasingly use subgenual anterior cingulate cortex (sgACC) functional connectivity to individualize treatment targets. However, the efficacy of this approach is unclear, with conflicting findings and varying effect sizes across studies. Here, the authors investigated the effect of the stimulation site's functional connectivity with the sgACC (sgACC-StimFC) on treatment outcome to rTMS in 295 patients with major depression. The reliability and accuracy of estimating sgACC functional connectivity were validated with data from individuals who underwent extensive functional MRI testing. Electric field modeling was used to analyze associations between sgACC-StimFC and clinical improvement using standardized assessments and to evaluate sources of heterogeneity. An imputation-based method provided reliable and accurate sgACC functional connectivity estimates. Treatment responses weakly but robustly correlated with sgACC-StimFC (r=−0.16), but only when the stimulated cortex was identified using electric field modeling. Surprisingly, this association was driven by patients with strong global signal fluctuations stemming from a specific periodic respiratory pattern (r=−0.49). Functional connectivity between the sgACC and the stimulated cortex was correlated with individual differences in treatment outcomes, but the association was weaker than those observed in previous studies and was accentuated in a subgroup of patients with distinct, respiration-related signal patterns in their scans. These findings indicate that in a large representative sample of patients with major depressive disorder, individual differences in sgACC-StimFC explained only ∼3% of the variance in outcomes, which may limit the utility of existing sgACC-based targeting protocols. However, these data also provide strong evidence for a true—albeit small—effect and highlight opportunities for incorporating additional functional connectivity measures to generate models of rTMS response with enhanced predictive power. [ABSTRACT FROM AUTHOR]

Purpose: To determine if there was a higher percentage of patients treated surgically and with advanced radiotherapy in 2016 (N = 897) versus 2009 (N = 1136), the patient and tumor characteristics associated with surgical care and advanced radiotherapy, and if chemotherapy or targeted agent use varied over time for squamous cell carcinoma of the head and neck. Methods: We utilized Surveillance Epidemiology and End Results Patterns of Care datasets. Rao-Scott Chi-square tests and logistic regressions were applied to determine differences in surgery, advanced radiotherapy (RT), and chemotherapy by year. Results: There was a lower prevalence of surgery only treatment in 2016 versus 2009 with exception of oral cavity stages IVB/IVC and unknown, and larynx stage unknown. Advanced RT was more common in 2016 for patients receiving definitive RT among all sites, excluding stages I/II glottic larynx. Among each site (oral cavity, oropharynx, and larynx) lower stage was associated with increased odds of surgery. Among each site, advanced RT was more common in patients receiving definitive versus postoperative RT. For the larynx site, 2016 versus 2009 was associated with greater odds of advanced RT. Systemic treatment with fluorouracil, taxanes, or cetuximab was less prevalent in 2016. Conclusion: In 2016 versus 2009, there was largely not a higher percentage of patients treated surgically. There was a higher prevalence of advanced RT for definitive care. Further investigations of these patterns are needed, including trend analysis. [ABSTRACT FROM AUTHOR]

In this effort, we present a fully energy autonomous two-way repeater system for use in nonline-of-sight (NLOS) interrogation of wireless sensor networks. The proposed system is based on a pair of tunnel diode reflection amplifiers, taking advantage of the existence of a negative differential resistance region that exists when the device is biased at a low voltage in the quantum tunneling region. This enables the development of an ultralow-cost, ultralow-power means to provide amplification. The proposed system demonstrates an ability to extend the total read range of semipassive radio frequency identification (RFID) tags by 4.55 times while consuming over 1000 times less power than comparable technologies, a notable improvement on previously published work. The system shows an ability to be customized to fit a wide array of different applications where NLOS interrogation and the read range of semipassive RFID tags pose a challenge. [ABSTRACT FROM AUTHOR]

We aim to evaluate the impact gynecologic oncologists have on ovarian cancer adjuvant chemotherapy care from their role as surgeons recommending adjuvant chemotherapy care and their role as adjuvant chemotherapy providers while considering rural-urban differences. Multivariable adjusted logistic regressions and Cox proportional hazards models were developed using a population-based, retrospective cohort of stage II-IV and unknown stage ovarian cancer patients diagnosed in Iowa, Kansas, and Missouri in 2010–2012 whose medical records were abstracted in 2017–2018. Gynecologic oncologist surgeons (versus other type of surgeon) were associated with increased odds of adjuvant chemotherapy initiation (adjusted odds ratio (OR) 2.18; 95% confidence interval (CI) 1.10–4.33) and having a gynecologic oncologist adjuvant chemotherapy provider (OR 10.0; 95% CI 4.58–21.8). Independent of type of surgeon, rural patients were less likely to have a gynecologic oncologist chemotherapy provider (OR 0.52; 95% CI 0.30–0.91). Gynecologic oncologist adjuvant chemotherapy providers (versus other providers) were associated with decreased surgery-to-chemotherapy time (rural: 6 days; urban: 8 days) and increased distance to chemotherapy (rural: 22 miles; urban: 11 miles). Rural women (versus urban) traveled 38 miles farther when their chemotherapy provider was a gynecologic oncologist and 27 miles farther when it was not. Gynecologic oncologist surgeons may impact adjuvant chemotherapy initiation. Gynecologic oncologists serving as adjuvant chemotherapy providers were associated with some care benefits, such as reduced time from surgery-to-chemotherapy, and some care barriers, such as travel distance. The barriers and benefits of having a gynecologic oncologist involved in adjuvant chemotherapy care, including rural-urban differences, warrant further research in other populations. • Gynecologic oncologist surgeons were associated with increased odds of initiating adjuvant chemotherapy. • Gynecologic oncologist surgeons were associated with greater odds of a gynecologic oncologist chemotherapy provider. • Gynecologic oncologist adjuvant chemotherapy providers were associated with decreased time from surgery-to-chemotherapy. • Rural and urban women traveled farther to receive chemotherapy care with gynecologic oncologist. • Rural women (versus urban) had a gynecologic oncologist involved in their adjuvant chemotherapy less and traveled farther. [ABSTRACT FROM AUTHOR]

Up to one-third of women with ovarian cancer in the United States do not receive surgical care from a gynecologic oncologist specialist despite guideline recommendations. We aim to investigate the impact of rurality on receiving surgical care from a specialist, referral to a specialist, and specialist surgery after referral, and the consequences of specialist care. We utilized a retrospective cohort created through an extension of standard cancer surveillance in three Midwestern states. Multivariable adjusted logistic regression was utilized to assess gynecologic oncologist treatment of women 18–89 years old, who were diagnosed with primary, histologically confirmed, malignant ovarian cancer in 2010–2012 in Kansas, Missouri and Iowa by rurality. Rural women were significantly less likely to receive surgical care from a gynecologic oncologist specialist (adjusted odds ratio (OR) 0.37, 95% confidence interval (CI) 0.24–0.58) and referral to a specialist (OR 0.37, 95% CI 0.23–0.59) compared to urban women. There was no significant difference in specialist surgery after a referral (OR 0.56, 95% CI 0.26–1.20). Rural women treated surgically by a gynecologic oncologist versus non-specialist were more likely to receive cytoreduction and more complete tumor removal to ≤1 cm. There is a large rural-urban difference in receipt of ovarian cancer surgery from a gynecologic oncologist specialist (versus a non-specialist). Disparities in referral rates contribute to the rural-urban difference. Further research will help define the causes of referral disparities, as well as promising strategies to address them. • Rural ovarian cancer patients are 63% less likely to receive a referral to a gynecologic oncologist for surgery • Rural ovarian cancer patients are significantly less likely to receive surgery from a gynecologic oncologist • After a surgical referral, rural ovarian cancer patients are just as likely to receive surgery from a specialist • Specialist-provided surgery increases receipt of cytoreduction and complete tumor removal for rural ovarian cancer patients • Rural women (versus urban) who receive surgery from a gynecologic oncologist travel farther to surgical care [ABSTRACT FROM AUTHOR]

Depression is a highly heterogeneous syndrome that bears only modest correlations with its biological substrates, motivating a renewed interest in rethinking our approach to diagnosing depression for research purposes and new efforts to discover subtypes of depression anchored in biology. Here, we review the major causes of diagnostic heterogeneity in depression, with consideration of both clinical symptoms and behaviors (symptomatology and trajectory of depressive episodes) and biology (genetics and sexually dimorphic factors). Next, we discuss the promise of using data-driven strategies to discover novel subtypes of depression based on functional neuroimaging measures, including dimensional, categorical, and hybrid approaches to parsing diagnostic heterogeneity and understanding its biological basis. The merits of using resting-state functional magnetic resonance imaging functional connectivity techniques for subtyping are considered along with a set of technical challenges and potential solutions. We conclude by identifying promising future directions for defining neurobiologically informed depression subtypes and leveraging them in the future for predicting treatment outcomes and informing clinical decision making. [ABSTRACT FROM AUTHOR]

Objectives: The role of HPV in oral cavity cancers was investigated using two markers of viral exposure.Materials and Methods: HPV DNA and p16INK4a expression were evaluated in tumor tissue from a U.S. population-based sample of 122 invasive oral cavity cancer cases.Results: HPV DNA was detected in 38 of 122 (31%) oral cavity tumors. Seven genotypes were detected including HPV 16, which was found in 22% of tumors. p16INK4a was expressed in 30% of tumors and was poorly correlated with HPV DNA detection (Kappa <0.1). Joint positivity for HPV 16 and/or 18 and p16INK4a was observed in only 7% of cases. When comparing cases diagnosed in 1993-1999 and in 2000-2004, positivity for HPV DNA 16/18 increased from 19% to 39% (p = 0.02) and joint HPV 16/18 - p16INK4a positivity increased from 0% to 12% (p = 0.01). For gingival tumors, HPV 16 and/or 18 positivity was 67% compared to 11-38% for other sites (p = 0.02); joint HPV 16/18 - p16INK4a positivity was 33% compared to 0-8% for other sites (p = 0.01). The association of HPV with gingival tumors and more recent diagnosis period remained after adjustment for age and stage (p < 0.05). Neither HPV DNA nor p16INK4a were associated with overall survival.Conclusions: Based on both HPV DNA and p16INK4a, HPV is etiologically linked to a limited subset of oral cavity cancers. However, the role of HPV in oral cavity cancer may vary widely by subsite and may have increased over time, similar to trends observed for oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Inorganic arsenic is a toxic naturally occurring element in soil and water in many regions of the US including the Midwest. Prostate cancer is the second most common type of cancer in men in Iowa, surpassed only by non-melanotic skin cancer. Epidemiology studies have evaluated arsenic exposure from drinking water and prostate cancer, but most have focused on high-level exposures outside the US. As drinking water from groundwater sources is a major source of arsenic exposure, we conducted an ecologic study to evaluate prostate cancer and arsenic in drinking water from public water sources and private wells in Iowa, where exposure levels are low, but duration of exposure can be long. Arsenic data from public water systems were obtained from the Iowa Safe Drinking Water Information System for the years 1994–2003 and for private wells from two Iowa Well Water Studies, the Iowa Community Private Well Study (ICPWS, 2002–2003) and Iowa Statewide Rural Well Water Survey Phase 2 (SWIRL2, 2006–2008) that provided data for 87 Iowa counties. Prostate cancer incidence data from 2009 to 2013 for Iowa were obtained from Surveillance, Epidemiology and End Results’ SEER*Stat software. County averages of water arsenic levels varied from 1.08 to 18.6 ppb, with three counties above the current 10 ppb limit. Based on the tertiles of arsenic levels, counties were divided into three groups: low (1.08–2.06 ppb), medium (2.07–2.98 ppb), and high (2.99–18.6 ppb). Spatial Poisson regression modeling was conducted to estimate the risk ratios (RR) of prostate cancer by tertiles of arsenic level at a county level, adjusted for demographic and risk factors. The RR of prostate cancer were 1.23 (95% CI, 1.16–1.30) and 1.28 (95% CI, 1.21–1.35) in the medium and high groups, respectively, compared to the low group after adjusting for risk factors. The RR increased to 1.36 (95% CI, 1.28–1.45) in the high group when analyses were restricted to aggressive prostate cancers (Gleason score ≥ 7). This study shows a significant dose-dependent association between low-level arsenic exposure and prostate cancer, and if this result is replicated in future individual-level studies, may suggest that 10 ppb is not protective for human health. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is used to treat multiple psychiatric and neurological conditions by manipulating activity in particular brain networks and circuits, but individual responses are highly variable. In clinical settings, TMS coil placement is typically based on either group average functional maps or scalp heuristics. Here, we found that this approach can inadvertently target different functional networks in depressed patients due to variability in their functional brain organization. More precise TMS targeting should be feasible by accounting for each patient's unique functional neuroanatomy. To this end, we developed a targeting approach, termed targeted functional network stimulation (TANS). The TANS approach improved stimulation specificity in silico in 8 highly sampled patients with depression and 6 healthy individuals and in vivo when targeting somatomotor functional networks representing the upper and lower limbs. Code for implementing TANS and an example dataset are provided as a resource. • Current TMS targeting approaches stimulate different functional networks across patients • A method for selective stimulation of patient-specific functional networks is introduced • Targeted functional network stimulation (TANS) improves stimulation specificity • Code for implementing TANS and an example dataset are provided as a public resource Transcranial magnetic stimulation (TMS) is used to treat multiple psychiatric and neurological conditions by manipulating activity in particular brain networks and circuits. Lynch et al. demonstrate that more precise TMS targeting is possible by accounting for each patient's unique functional neuroanatomy and cortical folding patterns using their method called targeted functional network stimulation (TANS). [ABSTRACT FROM AUTHOR]

Recipients of kidney transplantation have elevated risk of developing cancer. There are limited data on cancer risk in recipients of kidney retransplantation. We used data from the Transplant Cancer Match Study, which links the U.S. transplant registry with 15 cancer registries. Cancer incidence in recipients of kidney retransplantation and primary kidney transplants was compared utilizing Poisson regression, adjusting for demographic and medical characteristics. We assessed 109 224 primary recipients and 6621 retransplants. Compared to primary recipients, retransplants were younger (median age 40 vs. 46 yr), had higher PRA, and more often received induction with polyclonal antibodies (43% vs. 25%). A total of 5757 cancers were observed in primary recipients and 245 in retransplants. Overall cancer risk was similar in retransplants compared with primary recipients (incidence rate ratio [ IRR] 1.06, 95% CI 0.93-1.20, adjusted for age, gender, race/ethnicity, PRA, and use of polyclonal induction). However, renal cell carcinoma ( RCC) occurred in excess among retransplants (adjusted IRR 2.03, 95% CI 1.45-2.77), based on 514 cases in primary recipients and 43 cases in retransplants. Overall cancer risk did not differ in retransplants compared to primary recipients. Increased risk of RCC may be explained by the presence of acquired cystic kidney disease, which is more likely to develop with additional time with kidney disease and time spent on dialysis waiting for retransplantation. [ABSTRACT FROM AUTHOR]

Aging is a natural process involving complex interplay between environment, metabolism, and genes. Sirtuin genes and their downstream targets have been associated with lifespan in numerous organisms from nematodes to humans. Several target proteins of the sirtuin genes are key sensors and/or effectors of oxidative stress pathways including FOXO3, SOD3, and AKT1. To examine the relationship between single nucleotide polymorphisms (SNP) at candidate genes in these pathways and human lifespan, we performed a molecular epidemiologic study of an elderly cohort (≥65 years old.). Using age at death as a continuous outcome variable and assuming a co-dominant genetic model within the framework of multi-variable linear regression analysis, the genotype-specific adjusted mean age at death was estimated for individual SNP genotypes while controlling for age-related risk factors including smoking, body mass index, alcohol consumption and co-morbidity. Significant associations were detected between human lifespan and SNPs in genes SIRT3, SIRT5, SIRT6, FOXO3 and SOD3. Individuals with either the CC or CT genotype at rs107251 within SIRT6 displayed >5-year mean survival advantages compared to the TT genotype (5.5 and 5.9 years, respectively; q-value  = 0.012). Other SNPs revealed genotype-specific mean survival advantages ranging from 0.5 to 1.6 years. Gender also modified the effect of SNPs in SIRT3, SIRT5 and AKT1 on lifespan. Our novel findings highlight the impact of sirtuins and sirtuin-related genotypes on lifespan, the importance of evaluating gender and the advantage of using age as a continuous variable in analyses to report mean age at death. [ABSTRACT FROM AUTHOR]

Background: Conditional survival measures change in the risk of mortality given that a patient has survived a defined period of time. This has yet to be reported for chondrosarcoma of bone. This information should be of interest to the clinician and helpful in counseling patients with chondrosarcoma. Questions/purposes: Our questions include the following: (1) Does the conditional survival of patients with local/regional chondrosarcoma improve with each additional year of survival? (2) Does the conditional survival of patients with metastatic chondrosarcoma improve with each additional year of survival? (3) Does tumor location, use of radiation, or patient age affect conditional survival? (4) Can chondrosarcoma ever be considered cured? Methods: We used the Surveillance, Epidemiology, and End Results Program database maintained by the National Cancer Institute to identify 2138 patients with chondrosarcoma of bone from 1973 to 2009. We used an actuarial life table analysis to explore differences in 5-year cause-specific survival estimates conditional on 1 to 5 years of survival. The cohort was stratified by grade, location (axial versus extremity), use of radiation, and age. Finally, we expanded the analysis to include survival estimates 20 years after diagnosis conditional on survival for 5 and 10 years. Results: The estimated survival for all grades of local/regional chondrosarcoma improved from baseline with each year of survival after diagnosis. At 5 years after diagnosis, local/regional Grade 1 chondrosarcoma displayed higher conditional survival than Grade 2 and 3 local/regional chondrosarcoma (97.2% [95% confidence interval {CI}, 95.2%-98.4%] versus 92.8% [95% CI, 89.5%-95.0%], p = 0.006 and 83.8% [95% CI, 69.9%-91.7%], p = 0.012). Estimated survival improved from baseline with each year of survival for all grades of metastatic chondrosarcoma. Conditional survival estimates for Grade 3 axial tumors failed to improve from baseline to 5 years after diagnosis (52.9% versus 70.2%, p > 0.05) compared with Grade 3 extremity tumors at baseline and 5 years after diagnosis (58.1% versus 95.8%, p < 0.0001) The 20-year conditional survival estimates reveal that a cancer-specific risk of mortality exists even 10 years after diagnosis, suggesting that although the conditional survival increases considerably over time, it cannot be considered cured. Conclusions: The 5-year conditional survival estimate for patients with chondrosarcoma improved with each additional year of survival regardless of grade, site, age, or use of radiation. At 10 years after diagnosis, deaths attributable to cancer were still present, and patients should be aware of this small long-term risk. Level of Evidence: Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Conditional survival is a measure of the risk of mortality given that a patient has survived a defined period of time. These estimates are clinically helpful, but have not been reported previously for osteosarcoma or Ewing's sarcoma. Questions/purposes: We determined the conditional survival of patients with osteosarcoma and Ewing's sarcoma given survival of 1 or more years. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program database to investigate cases of osteosarcoma and Ewing's sarcoma in patients younger than 40 years from 1973 to 2009. The SEER Program is managed by the National Cancer Institute and provides survival data gathered from population-based cancer registries. We used an actuarial life table analysis to determine any cancer cause-specific 5-year survival estimates conditional on 1 to 5 years of survival after diagnosis. We performed a similar analysis to determine 20-year survival from the time of diagnosis. Results: The estimated 5-year survival improved each year after diagnosis. For local/regional osteosarcoma, the 5-year survival improved from 74.8% at baseline to 91.4% at 5 years-meaning that if a patient with localized osteosarcoma lives for 5 years, the chance of living for another 5 years is 91.4%. Similarly, the 5-year survivals for local/regional Ewing's sarcoma improved from 72.9% at baseline to 92.5% at 5 years, for metastatic osteosarcoma 35.5% at baseline to 85.4% at 5 years, and for metastatic Ewing's sarcoma 31.7% at baseline to 83.6% at 5 years. The likelihood of 20-year cause-specific survival from the time of diagnosis in osteosarcoma and Ewing's sarcoma was almost 90% or greater after 10 years of survival, suggesting that while most patients will remain disease-free indefinitely, some experience cancer-related complications years after presumed eradication. Conclusions: The 5-year survival estimates of osteosarcoma and Ewing's sarcoma improve with each additional year of patient survival. Knowledge of a changing risk profile is useful in counseling patients with time. The presence of cause-specific mortality decades after treatment supports lifelong monitoring in this population. Level of Evidence: Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: The default mode network (DMN), a brain system anchored in the posteromedial cortex, has been identified as underconnected in adults with autism spectrum disorder (ASD). However, to date there have been no attempts to characterize this network and its involvement in mediating social deficits in children with ASD. Furthermore, the functionally heterogeneous profile of the posteromedial cortex raises questions regarding how altered connectivity manifests in specific functional modules within this brain region in children with ASD. Methods: Resting-state functional magnetic resonance imaging and an anatomically informed approach were used to investigate the functional connectivity of the DMN in 20 children with ASD and 19 age-, gender-, and IQ-matched typically developing (TD) children. Multivariate regression analyses were used to test whether altered patterns of connectivity are predictive of social impairment severity. Results: Compared with TD children, children with ASD demonstrated hyperconnectivity of the posterior cingulate and retrosplenial cortices with predominately medial and anterolateral temporal cortex. In contrast, the precuneus in ASD children demonstrated hypoconnectivity with visual cortex, basal ganglia, and locally within the posteromedial cortex. Aberrant posterior cingulate cortex hyperconnectivity was linked with severity of social impairments in ASD, whereas precuneus hypoconnectivity was unrelated to social deficits. Consistent with previous work in healthy adults, a functionally heterogeneous profile of connectivity within the posteromedial cortex in both TD and ASD children was observed. Conclusions: This work links hyperconnectivity of DMN-related circuits to the core social deficits in young children with ASD and highlights fundamental aspects of posteromedial cortex heterogeneity. [ABSTRACT FROM AUTHOR]

Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotientmatched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between righthemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voiceselective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Wildland fires present many injury hazards to firefighters. We estimate injury rates and identify fire-related factors associated with injury. Methods: Data from the National Interagency Fire Center from 2003 to 2007 provided the number of injuries in which the firefighter could not return to his or her job assignment, person-days worked, and fire characteristics (year, region, season, cause, fuel type, resistance to control, and structures destroyed). We assessed fire-level risk factors of having at least one reported injury using logistic regression. Negative binomial regression was used to examine incidence rate ratios associated with fire-level risk factors. Results: Of 867 fires, 9.5% required the most complex management and 24.7% required the next-highest level of management. Fires most often occurred in the western United States (82.8%), during the summer (69.6%), caused by lightening (54.9%). Timber was the most frequent fuel source (40.2%). Peak incident management level, person-days of exposure, and the fire''s resistance to control were significantly related to the odds of a fire having at least one reported injury. However, the most complex fires had a lower injury incidence rate than less complex fires. Conclusions: Although fire complexity and the number of firefighters were associated with the risk for at least one reported injury, the more experienced and specialized firefighting teams had lower injury incidence. [Copyright &y& Elsevier]

Background: Melanoma rates continue to increase; however, few risk factors other than sun sensitivity and ultraviolet radiation (including sun exposure) have been identified. Although studies of farmers have shown an excess risk of melanoma and other skin cancers, it is unclear how much of this is related to sun exposure compared with other agricultural exposures. Methods: We examined dose-response relationships for 50 agricultural pesticides and cutaneous melanoma incidence in the Agricultural Health Study cohort of licensed pesticide applicators, along with ever use of older pesticides that contain arsenic. Logistic regression was used to examine odds ratios (ORs) and 95% confidence intervals (CIs) associated with pesticide exposure adjusted for age, sex, and other potential confounders. Results: We found significant associations between cutaneous melanoma and maneb/mancozeb (≥ 63 exposure days: OR = 2.4; 95% CI, 1.2-4.9; trend p = 0.006), parathion (≥ 56 exposure days: OR = 2.4; 95% CI, 1.3-4.4; trend p = 0.003), and carbaryl (≥ 56 exposure days: OR = 1.7; 95% CI, 1.1-2.5; trend p = 0.013). Other associations with benomyl and ever use of arsenical pesticides were also suggested. Conclusions: Most previous melanoma literature has focused on host factors and sun exposure. Our research shows an association between several pesticides and melanoma, providing support for the hypotheses that agricultural chemicals may be another important source of melanoma risk. [ABSTRACT FROM AUTHOR]

The authors conducted a population-based case-control study in Iowa of 375 brain cancer patients and 2, 434 controls. A postal questionnaire was used to gather information on lifetime residential history, sources of drinking water, beverage intake, and other potential risk factors. Exposure to chlorination byproducts in drinking water was estimated by combining questionnaire data with historical information from water utilities and trihalomethane levels in recent samples. The analysis included 291 cases (77.6%) and 1, 983 controls (81.5%), for whom water quality information was available for at least 70% of lifetime years. Proxies represented 74.4% of cases. The mean number and mean duration of places of residence were comparable between direct and proxy respondents, suggesting little contribution to bias. After multivariate adjustment, odds ratios for brain cancer were 1.0, 1.1, 1.6, and 1.3 for exposure to chlorinated surface water of 0, 1-19, 20-39, and ≥40 years (p trend = 0.1). Among men, odds ratios were 1.0, 1.3, 1.7, and 2.5 (p trend = 0.04), and among women, 1.0, 1.0, 1.6, and 0.7 (p trend = 0.7)). Similar findings were found with estimates of average lifetime level of trihalomethanes. The association was stronger among men with above-median tap water consumption. These observations deserve further attention, especially in view of increasing glioma rates. Am J Epidemiol 1999: 150: 552-60. [ABSTRACT FROM PUBLISHER]

Context: The Agricultural Health Study (AHS) is a large, prospective cohort study in the states of Iowa and North Carolina that has been developed to better understand how pesticides and other agricultural exposures relate to the occurrence of cancer and other diseases. Purpose: This report compares the characteristics of AHS farmers to the Census of Agriculture to evaluate the generalizability of AHS findings. Methods: We restricted the AHS to private pesticide applicators who enrolled in Iowa (n = 31,065) and in North Carolina (n = 17,239) between 1993 and 1997, and who identified themselves as living or working on a farm. We compared their self-reported data with data from the 1992 and 1997 Censuses of Agriculture. Findings: AHS farmers in Iowa are younger; live or work on larger farms; more frequently apply herbicides, insecticides, and fungicides; and are more likely to raise beef cattle and swine, and grow corn, soybeans, hay, and oats. AHS farmers in North Carolina are also younger, live or work on larger farms, more frequently reported growing crops commonly seen in the state, and are more frequent pesticide users. However, animals raised are similar to those in the North Carolina Census of Agriculture. Conclusions: AHS farmers likely represent the higher end of pesticide usage in both states in part because AHS farmers have larger farms. Since the health effects of pesticides are best ascertained among pesticide users with the greatest exposure, the AHS cohort should prove to be a valuable resource for health effects research. [ABSTRACT FROM AUTHOR]

Objectives. To quantify the relationship between prostatitis and prostate cancer by pooling previous epidemiologic studies of this association.Methods. A comprehensive search for articles published through 2000 was performed, blinded reviews of each study were conducted, data were abstracted, and all such studies were pooled.Results. In this meta-analysis, an increased risk was seen among men with a history of prostatitis (odds ratio = 1.6), particularly with population-based case-control studies (odds ratio = 1.8). Increased relative risk estimates were also seen among men with a history of syphilis and a history of gonorrhea.Conclusions. These associations with prostate cancer suggest that infections may represent one mechanism through which prostate cancer develops. However, causality is unclear, because recall bias and detection bias cannot be ruled out. Future cohort studies of prostate cancer should examine sexually transmitted infections, as well as other infections, as potential risk factors. [Copyright &y& Elsevier]

PURPOSE: The relative absence of racial/ethnic minorities among medical research subjects is receiving considerable attention because of recent government mandates for their inclusion in all human subject research. We examined racial differences in the prevalence of sociocultural barriers as a possible explanation for the underrepresentation of African Americans in medical research studies.METHODS: During 1998–1999, a total of 198 residents of the Detroit Primary Metropolitan Statistical Area (PMSA) participated in a survey that examined impediments to participation in medical research studies. Chi square tests and logistic regression analyses were used to examine the association between race, issues related to trust of medical researchers, and the willingness to participate in medical research studies.RESULTS: Study results indicate that African Americans and whites differ in their willingness to participate in medical research. Racial differences in the willingness to participate in a medical research are primarily due to the lower level of trust of medical research among African Americans. African American respondents were also somewhat less willing to participate if they attribute high importance to the race of the doctor when seeking routine medical care, believed that minorities bear most of the risks of medical research, and if their knowledge of the Tuskegee Study resulted in less trust in medical researchers.CONCLUSION: These data reiterate the need for medical researchers to build trusting relationships with minority communities. Researchers can begin by acknowledging the previous medical abuse of minority research participants, discussing their specific plans to assure the protection of study participants, and explaining the need for the participation of racial/ethnic minorities including studies that specifically target or that are likely to result in disproportionate representation of racial/ethnic minorities among study participants. [Copyright &y& Elsevier]

Investigates the factors possibly responsible for the low participation levels of African Americans in medical research studies and highlight areas for further research. Methods used in the study; Factors identified as possible impediments to African American participation; Effective recruitment strategies.

Driver's license lists are infrequently used for population-based sampling, presumably because of suspicions of poor population coverage. The 1990 Iowa driver's license list was compared with the 1990 census to evaluate coverage by 5-year age group, sex, resident county, and urbanicity. Coverage exceeded 90% among 15- to 74-year-old men and 15- to 64-year-old women, with uniform coverage by county and county urbanicity group in these age ranges. In Iowa, these lists are convenient and cost-effective and appear to be representative for 25- to 64-year-olds. The representativeness of driver lists in regard to other factors and in other geographic regions deserves further evaluation. [ABSTRACT FROM AUTHOR]

Evaluates the epidemiologic study of fluoride in drinking water in the municipalities in the State of Iowa. Implications of controlled fluoridation municipalities on treatment practices such as chlorination; Correlation between natural fluoride drinking water concentrations and water source depth; Significance in the evaluation of safety of fluoride in drinking water on water treatment processes.

Breathing rate and depth influence the concentration of carbon dioxide in the blood, altering cerebral blood flow and thus functional magnetic resonance imaging (fMRI) signals. Such respiratory fluctuations can have substantial influence in studies of fMRI signal covariance in subjects at rest, the so-called "resting state functional connectivity" technique. If respiration is monitored during fMRI scanning, it is typically done using a belt about the subject's abdomen to record abdominal circumference. Several measures have been derived from these belt records, including the windowed envelope of the waveform (ENV), the windowed variance in the waveform (respiration variation, RV), and a measure of the amplitude of each breath divided by the cycle time of the breath (respiration volume per time, RVT). Any attempt to gauge respiratory contributions to fMRI signals requires a respiratory measure, but little is known about how these measures compare to each other, or how they perform beyond the small studies in which they were initially proposed. Here, we examine the properties of these measures in hundreds of healthy young adults scanned for an hour each at rest, a subset of the Human Connectome Project chosen for having high-quality physiological records. We find: 1) ENV, RV, and RVT are all correlated, and ENV and RV are more highly correlated to each other than to RVT; 2) respiratory events like deep breaths exhibit characteristic heart rate elevations, fMRI signal changes, head motions, and image quality abnormalities time-locked to large deflections in the belt traces; 3) all measures can "miss" deep breaths; 4) RVT "misses" deep breaths more than ENV or RV; 5) all respiratory measures change systematically over the course of a 14.4-min scan. We discuss the implications of these findings for the literature and ways to move forward in modeling respiratory influences on fMRI scans. • Data are resting state fMRI scans in healthy young adults. • Examines respiratory belt records and derived measures ENV, RV, and RVT. • All respiratory measures "miss" deep breaths, RVT more than others. • Deep breaths exhibit characteristic heart rate and fMRI signal changes. • All respiratory measures change systematically over 14.4 min scans. [ABSTRACT FROM AUTHOR]

Head motion estimates in functional magnetic resonance imaging (fMRI) scans appear qualitatively different with sub-second image sampling rates compared to the multi-second sampling rates common in the past. Whereas formerly the head appeared still for much of a scan with brief excursions from baseline, the head now appears to be in constant motion, and motion estimates often seem to divulge little information about what is happening in a scan. This constant motion has been attributed to respiratory oscillations that do not alias at faster sampling rates, and investigators are divided on the extent to which such motion is "real" motion or only "apparent" pseudomotion. Some investigators have abandoned the use of motion estimates entirely due to these considerations. Here we investigate the properties of motion in several fMRI datasets sampled at rates between 720 and 1160 ms, and describe 5 distinct kinds of respiratory motion: 1) constant real respiratory motion in the form of head nodding most evident in vertical position and pitch, which can be very large; 2) constant pseudomotion at the same respiratory rate as real motion, occurring only in the phase encode direction; 3) punctate real motions occurring at times of very deep breaths; 4) a low-frequency pseudomotion in only the phase encode direction at and after very deep breaths; 5) slow modulation of vertical and anterior-posterior head position by the respiratory envelope. We reformulate motion estimates in light of these considerations and obtain good concordance between motion estimates, physiologic records, image quality measures, and events evident in the fMRI signals. We demonstrate how variables describing respiration or body habitus separately scale with distinct kinds of head motion. We also note heritable aspects of respiration and motion. • Examines several fast-TR datasets with sampling rates of 720–1160 ms • Identifies 7 kinds of motion in fMRI scans, 5 of them related to respiration. • Identifies 2 forms of pseudomotion occurring only in the phase encode direction. • Pseudomotion is a function of soft tissue mass, not lung volume. • Reformulates motion estimates to draw out particular kinds of motion. [ABSTRACT FROM AUTHOR]

This study reports the types of firearms used in firearm suicides in Iowa and tests the hypothesis that the use of handguns, rifles, and shotguns in such suicides reflects the availability of these weapons. The percentage of firearm suicides involving handguns increased from 36.6% in 1980 through 1984 to 43.3% during 1990 and 1991. In both time periods, the use of handguns was more likely than would be expected from their household prevalence. Our data suggest that handguns are disproportionately represented among firearm suicides and that this over representation has increased during the last decade. [ABSTRACT FROM AUTHOR]

Background: Immunosuppressed solid organ transplant recipients (SOTRs) have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections.Methods: We performed a cohort study of 262 455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries. First cancers in SOTRs were categorized using an established classification scheme based on site and histology. Standardized incidence ratios (SIRs) compared risk in SOTRs with the general population. We used Poisson regression to calculate incidence rate ratios according to immune-related SOTR characteristics, including time since transplant (ie, duration of immunosuppression). All statistical tests were 2-sided.Results: We examined 694 distinct cancer subtypes, with 33 manifesting statistically significantly elevated SIRs (Bonferroni P < 7.2 × 10-5). All 33 are rare (incidence <6 per 100 000 person-years) and several have known viral etiology (eg, Merkel cell carcinoma: SIR = 24.7, 95% confidence interval [CI] = 20.8 to 29.1). Additional cancers that were increased include squamous cell carcinomas of the lip (SIR range = 18.3-19.8), eye and adnexa (SIR = 13.8, 95% CI = 7.9 to 22.3), salivary gland (SIR = 9.3, 95% CI = 6.1 to 13.5), and nasal cavity and sinuses (SIR = 4.5, 95% CI = 2.8 to 6.8); sebaceous adenocarcinoma (SIR = 34.3, 95% CI = 26.3 to 44.0); malignant fibrous histiocytoma (15.4); and subtypes of bladder, kidney, lung, and colon cancer (SIR range = 3.2-13.3). Incidence of several cancers increased over time since transplant (Ptrend < .05), including squamous cell carcinomas of the lip, salivary gland, and anogenital sites.Conclusions: SOTRs experience elevated rates of several rare cancers. Because some of these cancers exhibit aggressive behavior with poor outcomes, it is important to further characterize the role of immunity and the potential involvement of oncogenic viruses to improve prevention and treatment. [ABSTRACT FROM AUTHOR]

The article discusses the cancer risk following post-transplant lymphoproliferative disorders in solid organ transplant recipients. Topics include how post-transplant lymphoproliferative disorders (PTLDs) are associated with immunosuppressive therapy administered to prevent graft rejection, leading to uncontrolled replication of Epstein–Barr virus (EBV).

A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated. [ABSTRACT FROM AUTHOR]

Background: Transplant recipients have an elevated risk of cancer because of immunosuppressive medications used to prevent organ rejection, but to the authors' knowledge no study to date has comprehensively examined associations between transplantation status and mortality after a cancer diagnosis.Methods: The authors assessed cases in the US general population (N=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry (1987-2014). Cox models were used to examine the association between transplantation status and cancer-specific mortality, adjusting for demographic characteristics and cancer stage.Results: For the majority of cancers, cancer-specific mortality was higher in transplant recipients compared with other patients with cancer. The increase was particularly pronounced for melanoma (adjusted hazard ratio [aHR], 2.59; 95% confidence interval [95% CI], 2.18-3.00) and cancers of the breast (aHR, 1.88; 95% CI, 1.61-2.19), bladder (aHR, 1.85; 95% CI, 1.58-2.17), and colorectum (aHR, 1.77; 95% CI, 1.60-1.96), but it also was increased for cancers of the oral cavity/pharynx, stomach, pancreas, kidney, and lung as well as diffuse large B-cell lymphoma (aHR range, 1.21-1.47). Associations remained significant after adjustment for first-course cancer treatment and generally were stronger among patients with local-stage cancers for whom potentially curative treatment was provided, including patients with melanoma (aHR, 3.82; 95% CI, 2.94-4.97) and cancers of the colorectum (aHR, 2.77; 95% CI, 2.07-3.70), breast (aHR, 2.08; 95% CI, 1.50-2.88), and prostate (aHR, 1.60; 95% CI, 1.12-2.29), despite the lack of an association for prostate cancer overall.Conclusions: For multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage and treatment, which may be due to impaired immunity. [ABSTRACT FROM AUTHOR]

Background: Small tumor diagnostic tools including ultrasound-guided fine needle aspiration (FNA) and computed tomography (CT) could be causing rising and racially/ethnically different thyroid cancer incidence rates due to variable overdiagnosis of indolent tumors. Papillary tumors and <40 mm tumors are most likely to be overdiagnosed as indolent tumors by FNA and CT.Methods: Age-adjusted incidence rates (AAIRs) for the years 2007-2014 were calculated for race/ethnicity (white, Hispanic, Asian, African American, Native American) by patient/tumor characteristics for microscopically confirmed malignant thyroid cancer cases in the Surveillance, Epidemiology, and End Results Program 18 database (SEER 18; N = 93,607). Multivariate analysis determined cancer patients' odds ratios of diagnosis with papillary thyroid carcinoma (vs other histologies) and tumors <40 mm (vs ≥40 mm).Results: For both males and females, there were statistically significant differences in incidence rates between race/ethnicity, with whites having the highest AAIRs and African Americans the lowest AAIRs. Among thyroid cancer patients, tumor size and histology differed significantly by race and insurance coverage after controlling for age, sex, stage, and tumor sequence. Non-whites with thyroid cancer (vs whites) were less associated with small tumors (odds ratio [OR], 0.51-0.79; P < .0001). Medicaid and uninsured patients with thyroid cancer were less associated with tumors <40 mm (OR, 0.55-0.71; 95% confidence interval [CI], 0.49-0.76) and papillary carcinoma (OR, 0.86; 95% CI, 0.80-0.93).Conclusion: The diagnosis of small tumors is occurring at greater rates in whites (vs non-whites) and insured (vs Medicaid and uninsured) patients; consequently, these groups may be vulnerable to unnecessary tests and treatments or potentially aided by early detection. Guidelines that define postdetection interventions may be needed to limit the overtreatment of indolent and small papillary carcinomas. Cancer 2018;124:1483-91. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors, that are treated per risk profile. We sought to describe treatment patterns and survival using population-based data from throughout the United States. Materials and Methods: Using the National Cancer Institute (NCI)'s Patterns of Care data, we analyzed treatment provided to newly diagnosed, histologically confirmed neuroblastoma patients in 2010 and 2011, registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries. Data were re-abstracted from hospital records and treating physicians contacted for verification. Application of the Children's Oncology Group (COG)'s 3-level (low, intermediate and high) neuroblastoma risk classification system for therapeutic decision-making provided insight to community-based treatment patterns. Kaplan-Meier survival analyses, based on 5-years of follow-up, were also performed. Results: 76% of the 250 patients were enrolled on an open/active clinical trial. All low-risk patients received surgery. Most intermediate-risk patients (81%) received a chemotherapy regimen that included carboplatin, etoposide, cyclophosphamide and doxorubicin. High-risk patients received extensive, multimodal treatment consisting of chemotherapy, surgery, myeloablative chemotherapy with stem cell rescue (transplant), radiation, immunotherapy (dinutuximab), and isotretinoin therapy. 21% patients had died at the end of the maximum 60-month follow-up period. The 5-year estimated survival rates were lower for patients diagnosed with stage 4 disease, unfavorable DNA ploidy, MYCN gene amplification or classified as high-risk. Conclusion: Most neuroblastoma patients are registered on a risk-based open/active clinical trial. Variation in modality, systemic agents and sequence of treatment reflects the heterogeneity of therapy received by these patients. [ABSTRACT FROM AUTHOR]

Objective. Given the challenges rural cancer patients face in accessing cancer care as well as the slower diffusion and adoption of new medical technologies among rural providers, the aim of our study was to examine trends in gene expression profiling (GEP) testing and evaluate the association between hospital rurality and receipt of GEP testing. Methods. Data from the Iowa Cancer Registry (ICR) were used to identify women with newly diagnosed, histologically confirmed breast cancer from 2010 through 2018 who met eligibility criteria for GEP testing. Patients were allocated to the hospitals where their most definitive surgical treatment was received, and Rural-Urban Commuting Area codes were used to categorize hospitals into urban (N = 43), large rural (N = 16), and small rural (N = 48). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression to evaluate the association between hospital rurality and GEP test use, adjusting for demographic and clinical characteristics. The association between test result and treatment received was assessed among patients who received Oncotype DX (ODX) testing. Results. Of 6,726 patients eligible for GEP test use, 46% (N = 3,069) underwent testing with 95% receiving ODX. While overall GEP testing rates increased over time from 42% between 2010 and 2012 to 51% between 2016 and 2018 ( P trend < 0.0001), use continued to be the lowest among patients treated at hospitals in small rural areas. The odds of GEP testing remained significantly lower among patients treated at hospitals located in small rural areas (aOR 0.55; 95% CI 0.43–0.71), after adjusting for demographic and clinical characteristics. ODX recurrence scores were highly correlated with chemotherapy use across all strata of hospital rurality. Conclusions. GEP testing continues to be underutilized, especially among those treated at small rural hospitals. Targeted interventions aimed at increasing rates of GEP testing to ensure the appropriate use of adjuvant chemotherapy may improve health outcomes and lower treatment-related costs. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is characterized by reduced attention to salient social stimuli. Here, we use two visual oddball tasks to investigate brain systems engaged during attention to social (face) and non-social (scene) stimuli. We focused on the dorsal and ventral subdivisions of the anterior insula (dAI and vAI, respectively), anatomically distinct regions contributing to a 'salience network' that is known to regulate attention to behaviorally meaningful stimuli. Children with ASD performed comparably to their typically developing (TD) peers, but they engaged the right dAI and vAI differently in response to deviant faces compared with deviant scenes. Multivariate activation patterns in the dAI reliably discriminated between children with ASD and TD children with 85% classification accuracy, and children with ASD activated the vAI more than their TD peers. Children with ASD and their TD peers also differed in dAI connectivity patterns to deviant faces, with stronger within-salience network interactions in the ASD group and stronger cross-network interactions in the TD group. Our findings point to atypical patterns of right anterior insula activation and connectivity in ASD and suggest that multiple functions subserved by the insula, including attention and affective processing of salient social stimuli, are aberrant in children with the disorder. [ABSTRACT FROM AUTHOR]

Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic investigations, in 2010 the study of Biomarkers of Exposure and Effect in Agriculture (BEEA) was initiated within the Agricultural Health Study, a large prospective cohort in Iowa and North Carolina. Here the design and methodology of BEEA are described and preliminary frequencies for participant characteristics and current agricultural exposures are reported. At least 1,600 male farmers over 50 years of age will be enrolled in the BEEA study. During a home visit, participants are asked to complete a detailed interview about recent agricultural exposures and provide samples of blood, urine, and (since 2013) house dust. As of mid-September 2014, in total, 1,233 participants have enrolled. Most of these participants (83%) were still farming at the time of interview. Among those still farming, the most commonly reported crops were corn (81%) and soybeans (74%), and the most frequently noted animals were beef cattle (35%) and hogs (13%). There were 861 (70%) participants who reported occupational pesticide use in the 12 months prior to interview; among these participants, the most frequently noted herbicides were glyphosate (83%) and 2,4-D (72%), and most commonly reported insecticides were malathion (21%), cyfluthrin (13%), and permethrin (12%). Molecular epidemiologic investigations within BEEA have the potential to yield important new insights into the biological mechanisms through which these or other agricultural exposures influence disease risk. [ABSTRACT FROM PUBLISHER]

Examines the effects of misclassification on risk estimates of chlorinated drinking water and bladder cancer in Iowa. Contamination of water source; Assessment of hologynic organic compounds as byproducts of chlorination; Quantification of environmental exposure.

Precis Omission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients. Background: Despite national guidelines, debate exists among clinicians regarding the optimal approach to treatment for patients diagnosed with ductal carcinoma in situ (DCIS). While regional variation in practice patterns has been well documented, population‐based information on rural–urban treatment differences is lacking. Methods: Data from the SEER Patterns of Care studies were used to identify women diagnosed with histologically confirmed DCIS who underwent cancer‐directed surgery in the years 1991, 1995, 2000, 2005, 2010, and 2015. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using weighted multivariable logistic regression to evaluate cancer‐directed surgery and use of post‐operative radiation therapy (PORT). Results: Of the 3337 patients who met inclusion criteria, 27% underwent mastectomy, 26% underwent breast‐conserving surgery (BCS) without PORT, and 47% underwent BCS with PORT. After adjustment for other covariates, there was no difference in the likelihood of receiving mastectomy between rural and urban patients (aOR = 0.65; 95% CI 0.37–1.14). However, rural residents were more likely than urban residents to have mastectomy during 1991/1995 (aOR = 1.78; 95% CI 1.09–2.91; pinteraction = 0.022). Across all diagnosis years, patients residing in rural areas were less likely to receive PORT following BCS compared to urban patients (aOR = 0.35; 95% CI 0.18–0.67). Conclusions: Omission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients. [ABSTRACT FROM AUTHOR]

Evidence is mounting that cigarette smoking contributes to second primary contralateral breast cancer (CBC) risk. Whether radiation therapy (RT) interacts with smoking to modify this risk is unknown. In this multicenter, individually matched, case-control study, we examined the association between RT, smoking, and CBC risk. The study included 1521 CBC cases and 2212 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2008 aged younger than 55 years. Absorbed radiation doses to contralateral breast regions were estimated with thermoluminescent dosimeters in tissue-equivalent anthropomorphic phantoms, and smoking history was collected by interview. Rate ratios (RRs) and 95% confidence intervals (CIs) for CBC risk were estimated by multivariable conditional logistic regression. There was no interaction between any measure of smoking with RT to increase CBC risk (eg, the interaction of continuous RT dose with smoking at first breast cancer diagnosis [ever/never]: RR = 1.00, 95% CI = 0.89 to 1.14; continuous RT dose with years smoked: RR = 1.00, 95% CI = 0.99 to 1.01; and continuous RT dose with lifetime pack-years: RR = 1.00, 95% CI = 0.99 to 1.01). There was no evidence that RT further increased CBC risk in young women with first primary breast cancer who were current smokers or had smoking history. [ABSTRACT FROM AUTHOR]

Objectives: Neurologic complications of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) frequently lead to disability or death in affected patients. The aim of this study was to determine whether survival patterns differ between men and women with HIV/AIDS-related neurologic disease (neuro-AIDS). Methods: Retrospective cohort data from a statewide surveillance database for HIV/AIDS were used to characterize survival following an HIV/AIDS-related neurologic diagnosis for men and women with one or more of the following conditions: cryptococcosis, toxoplasmosis, primary central nervous system lymphoma, progressive multifocal leukoencephalopathy, and HIV-associated dementia. A second, non-independent cohort was formed using university-based cases to confirm and extend the findings from the statewide data. Kaplan-Meier analysis was used to compare the survival experiences for men and women in the cohorts. Cox regression was employed to characterize survival while controlling for potential confounders in the study population. Results: Women (n=27) had significantly poorer outcomes than men (n=198) in the statewide cohort (adjusted hazard ratio=2.31, 95% CI: 1.22 to 4.35), and a similar, non-significant trend was observed among university-based cases (n=17 women, 154 men). Secondary analyses suggested that this difference persisted over the course of the AIDS epidemic and was not attributable to differential antiretroviral therapy responses among men and women. Conclusions: The survival disadvantage of women compared to men should be confirmed and the mechanisms underlying this disparity elucidated. If this relationship is confirmed, targeted clinical and public health efforts might be directed towards screening, treatment, and support for women affected by neuro-AIDS. [ABSTRACT FROM AUTHOR]

Purpose: Human papillomavirus (HPV) is a major risk factor for specific cancers of the head and neck, particularly malignancies of the tonsil and base of the tongue. However, the role of HPV in the development of laryngeal cancer has not been definitively established. We conducted a population-based, cancer registry study to evaluate and characterize the genotype-specific prevalence of HPV in invasive laryngeal cancer cases diagnosed in the U.S. Methods: The presence of genotype-specific HPV DNA was evaluated using the Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay in formalin-fixed paraffin embedded tissue from 148 invasive laryngeal cancer cases diagnosed in 1993–2004 within the catchment area of three U.S. SEER cancer registries. Results: HPV DNA was detected in 31 of 148 (21%) invasive laryngeal cancers. Thirteen different genotypes were detected. Overall, HPV 16 and HPV 33 were the most commonly detected types. HPV was detected in 33% (9/27) of women compared with 18% (22/121) of men (p = 0.08). After adjustment for age and year of diagnosis, female patients were more likely to have HPV-positive laryngeal tumors compared to males (adjusted OR 2.84, 95% CI 1.07–7.51). Viral genotype differences were also observed between the sexes. While HPV 16 and 18 constituted half of HPV-positive cases occurring in men, among women, only 1 was HPV 16 positive and none were positive for HPV 18. Overall 5-year survival did not vary by HPV status. Conclusions: HPV may be involved in the development of a subset of laryngeal cancers and its role may be more predominant in women compared to men. [ABSTRACT FROM AUTHOR]

Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993–97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999–2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes. [ABSTRACT FROM AUTHOR]

Background: Solid organ transplant recipients have an elevated risk of cancer. Quantifying the life‐years lost (LYL) due to cancer provides a complementary view of the burden of cancer distinct from other metrics and may identify subgroups of transplant recipients who are most affected. Methods: Linked transplant and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987‐2014). Data on LYL due to cancer within 10 years posttransplant were derived using mean survival estimates from Cox models. Results: Among 221,962 transplant recipients, 13,074 (5.9%) developed cancer within 10 years of transplantation. During this period, the mean LYL due to cancer were 0.16 years per transplant recipient and 2.7 years per cancer case. Cancer was responsible for a loss of 1.9% of the total life‐years expected in the absence of cancer in this population. Lung recipients had the highest proportion of total LYL due to cancer (0.45%) followed by heart recipients (0.29%). LYL due to cancer increased with age, from 0.5% among those aged birth to 34 years at transplant to 3.2% among those aged 50 years and older. Among recipients overall, lung cancer was the largest contributor, accounting for 24% of all LYL due to cancer, and non‐Hodgkin lymphoma had the next highest contribution (15%). Conclusions: Transplant recipients have a shortened lifespan after developing cancer. Lung cancer and non‐Hodgkin lymphoma contribute strongly to LYL due to cancer within the first 10 years after transplant, highlighting opportunities to reduce cancer mortality through prevention and screening. Transplantation recipients have a shortened lifespan after developing cancer. Lung cancer and non‐Hodgkin lymphoma contribute strongly to life‐years lost due to cancer, highlighting opportunities to reduce cancer mortality in this population through prevention and screening. [ABSTRACT FROM AUTHOR]