Search

Tyrosine kinase inhibitors (TKI) are anticancer agents widely used for a variety of malignancies including gastrointestinal stromal tumours (GIST). Although generally well-tolerated, TKIs have been associated with a number of adverse events including hypertension, proteinuria and nephrotic syndrome. We present the case of a 70-year-old patient with metastatic GIST on long-standing sunitinib who developed hypertension, oedema and hypoalbuminemia with a rising serum creatinine and was found to have nephrotic syndrome. Workup revealed elevated antiphospholipase A2 receptor (PLA2R) antibody IgG titres and a kidney biopsy confirmed PLA2R-positive membranous nephropathy without findings of thrombotic microangiopathy. Cessation of sunitinib led to reduction in anti-PLA2R antibody IgG titres while resumption, due to concern for cancer progression, led to worsening symptoms. Treatment with rituximab led to undetectable anti-PLA2R IgG titres. We highlight the importance of maintaining a systematic approach for evaluating nephrotic syndrome and provide a case showing that TKIs can exacerbate underlying nephrotic syndrome.

Here we report a case of renal oncocytoma in a 68 year-old male. The diagnosis was initially made on a needle biopsy 6 years prior to the partial nephrectomy. The case is unique that in addition to the gross and microscopic features commonly seen in renal oncocytomas, both lymphovascular invasion and prominent intracytoplasmic vacuole-like spaces are also present in this tumor. Although vascular invasion is increasingly recognized as compatible with renal oncocytoma, intracytoplasmic vacuoles are a rare and unusual finding that may lead to diagnostic difficulty. The diagnosis of renal oncocytoma was confirmed after immunohistochemistry was performed to argue against succinate dehydrogenase deficient renal cell carcinoma (RCC) and chromophobe RCC. This case highlights the importance for practicing pathologists to recognize the rare co-occurrence of lymphovascular invasion and large intracytoplasmic vacuole-like spaces in renal oncocytoma. Other differential diagnoses may include emerging renal tumor entities, such as the recently-proposed eosinophilic vacuolated tumor.

The US Peace Corps has been operating programs globally since 1961 with an enduring mission toward international friendship and world peace structured around clear goals that emphasize cross-cultural learning objectives. Little is known about whether the program has a positive effect on US soft power abroad and, if so, the magnitude of that influence. This paper examines the impact of Peace Corps programming in foreign states on US public diplomacy objectives. The primary research aims to understand the relationship between indicators of a foreign population’s favorability toward the US and Peace Corps participation to determine the effects of program size as well as program presence and removal. Pew Research Center US favorability scores were analyzed alongside Peace Corps volunteer cohort sizes between years 2004 and 2016 among 20 sample countries. The findings indicate a positive and statistically significant relationship between the size of the Peace Corps volunteer cohort and US favorability. Each additional volunteer increases favorability toward the US by 0.12 points. The results are robust to the inclusion of additional soft power factors. Supplementary findings illustrate that the removal of Peace Corps programming may adversely impact favorability toward the US, establishing the negative soft power effect of ceasing participation.

To prospectively validate electromagnetic hand motion tracking in interventional radiology to detect differences in operator experience using simulation.Sheath task: Six attending interventional radiologists (experts) and 6 radiology trainees (trainees) placed a wire through a sheath and performed a "pin-pull" maneuver, while an electromagnetic motion detection system recorded the hand motion. Radial task: Eight experts and 12 trainees performed palpatory radial artery access task on a radial access simulator. The trainees repeated the task with the nondominant hand. The experts were classified by their most frequent radial artery access technique as having either palpatory, ultrasound, or overall limited experience. The time, path length, and number of movements were calculated. Mann-Whitney U tests were used to compare the groups, and P.05 was considered significant.Sheath task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (11.7 seconds ± 3.3 vs 19.7 seconds ± 6.5, P.01; 1.1 m ± 0.3 vs 1.4 m ± 0.4, P.01; and 19.5 movements ± 8.5 vs 31.0 movements ± 8.0, P.01, respectively). Radial task: The experts took less time, had shorter path lengths, and used fewer movements than the trainees (24.2 seconds ± 10.6 vs 33.1 seconds ± 16.9, P.01; 2.0 m ± 0.5 vs 3.0 m ± 1.9, P.001; and 36.5 movements ± 15.0 vs 54.5 movements ± 28.0, P.001, respectively). The trainees had a shorter path length for their dominant hand than their nondominant hand (3.0 m ± 1.9 vs 3.5 m ± 1.9, P.05). The expert palpatory group had a shorter path length than the ultrasound and limited experience groups (1.8 m ± 0.4 vs 2.0 m ± 0.4 and 2.3 m ± 1.2, respectively, P.05).Electromagnetic hand motion tracking can differentiate between the expert and trainee operators for simulated interventional tasks.

The application of deep learning for automated segmentation (delineation of boundaries) of histologic primitives (structures) from whole slide images can facilitate the establishment of novel protocols for kidney biopsy assessment. Here, we developed and validated deep learning networks for the segmentation of histologic structures on kidney biopsies and nephrectomies. For development, we examined 125 biopsies for Minimal Change Disease collected across 29 NEPTUNE enrolling centers along with 459 whole slide images stained with Hematoxylin & Eosin (125), Periodic Acid Schiff (125), Silver (102), and Trichrome (107) divided into training, validation and testing sets (ratio 6:1:3). Histologic structures were manually segmented (30048 total annotations) by five nephropathologists. Twenty deep learning models were trained with optimal digital magnification across the structures and stains. Periodic Acid Schiff-stained whole slide images yielded the best concordance between pathologists and deep learning segmentation across all structures (F-scores: 0.93 for glomerular tufts, 0.94 for glomerular tuft plus Bowman's capsule, 0.91 for proximal tubules, 0.93 for distal tubular segments, 0.81 for peritubular capillaries, and 0.85 for arteries and afferent arterioles). Optimal digital magnifications were 5X for glomerular tuft/tuft plus Bowman's capsule, 10X for proximal/distal tubule, arteries and afferent arterioles, and 40X for peritubular capillaries. Silver stained whole slide images yielded the worst deep learning performance. Thus, this largest study to date adapted deep learning for the segmentation of kidney histologic structures across multiple stains and pathology laboratories. All data used for training and testing and a detailed online tutorial will be publicly available.

The effects of mild dehydration during ice hockey are well-studied in males but not females. In a randomized, crossover design, 11 female varsity hockey players drank no fluid (1.7% ± 0.3% body mass loss) or water to maintain hydration during simulated-hockey exercise. Core temperature (P < 0.01) and perceived fatigue (P = 0.02) were higher and sprint power lower (P < 0.01) when mildly dehydrated. Thus, mild dehydration may impair hockey performance and thermoregulation while increasing perceived fatigue in females. Novelty Female stop-and-go sport athletes may benefit their in-game sprint performance and thermoregulation by following personalized in-game hydration to prevent becoming mildly dehydrated.

Objectives Persistent antigen exposure leads to the accumulation of lymphocytes and subsequent tertiary lymphoid structures (TLS). We investigated the relationship of tumor microenvironment (TME) with respect to programmed death ligand 1 (PD-L1), its receptor programmed death 1 (PD-1), and TLS in upper tract urothelial carcinoma (UTUC) cases and compared them with UTUC associated with urothelial bladder carcinoma (UTUC-BCa). Methods We retrospectively identified 72 patients with UTUC. Representative slides were reviewed, and TLS were counted. Immunohistochemical stains for PD-1 and PD-L1 were performed. PD-1–positive lymphocytes were counted and H-score for PD-L1–positive membranous staining was determined. Results PD-L1 expression in the tumor was present in 55.1% of the UTUC cases. Higher stage was associated with increased PD-L1 expression (P = .035). TLS were present in 33.3% and their presence was significantly associated with PD-L1 positivity (P = .024). This association remained significant after adjustment for UTUC-BCa. TLS were also associated with a greater number of infiltrating PD-1-positive lymphocytes (P = .013). Conclusions This study is one of the first comparative studies of the TME in UTUC and UTUC-BCa. PD-L1 is expressed in a subset of UTUC and is associated with TLS. The presence of TLS is an inherent characteristic of UTUC and not secondary to the presence of BCa.

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19) resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%) which associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19, demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney., Graphical abstract

This study measured sweat losses, voluntary fluid intake, sodium balance, and carbohydrate intake of female ice hockey players during on-ice practices at the Olympic, varsity, and recreational levels. Testing was conducted on 25 Canadian Olympic players, 21 varsity, and 21 recreational players. The average sweat rate for the Olympic players (0.99±0.08 L/h) was significantly greater than both the varsity (0.67±0.05 L/h, p=0.001) and the recreational players (0.42±0.03 L/h, p1.5% BM and 4 others lost>1% BM, with no players in both the varsity and recreational teams losing>1% BM. Half of the Olympic players consumed some carbohydrate during practice, but most of the varsity and recreational players did not. In conclusion, sweat rates in female ice hockey players during practices were proportional to competitive level. Fluid intake was similar between groups and resulted in only a few athletes at the Olympic level being at risk of excess body mass loss.

Marine robots have the potential to enhance WIO marine research to improve regional adaptation to the challenges presented by climate change by providing enhanced research capacity that bypasses the requirement for expensive infrastructure, such as large research vessels. This paper tests this potential and assesses the readiness of WIO communities to adopt autonomous technologies to meet its marine research priorities. We apply a range of analyses to a marine robots case study undertaken in waters around the island of Pemba, part of the Zanzibar archipelago, in Tanzania in 2019. The campaign formed part of a multinational project focused on increasing WIO capacity to meet food security and ocean sustainability challenges. A community engagement programme with six Tanzanian coastal communities resulted in positive changes in attitudes towards marine robots with reported increases in understanding and acceptance of such technologies. Suspicion of the robots was reduced and a lower risk of removing operational equipment was recorded following the provision of educational material. Cost, risk and benefit analysis shows that marine robots are perceived to provide high level benefits, but come at a high cost that is difficult to achieve using national or regional funding. An assessment of the capacity of WIO marine institutes to adopt such technologies shows that prior to this work, few skills or infrastructure related to marine robots were available to researchers and further confirmed that funding opportunities were perceived to be largely unavailable at institutional, national, regional or international levels. Responses from regional partners following completion of the case study however, revealed an uplift in perceived capacity, particularly related to access to infrastructure and expertise as well as support and opportunities for funding at each level. The presented case study is shown to have been a valuable demonstrator of the benefits of using marine robots to meet WIO coastal ocean research requirements and regional capacity was shown to be substantially increased within the broad range of marine institutes surveyed throughout the case study period. This study demonstrates that taking early steps towards adopting marine autonomous robots has increased WIO regional marine research capacity and increased the confidence and willingness of local researchers to seek alternative solutions to ongoing marine research challenges. Recommendations for future action that will continue to increase the capacity and readiness for regional adoption of marine robots include investment at local, national and regional levels to provide accessible training opportunities and to facilitate regional and international collaborations; investment in a regional hub, or centre of excellence for marine robotic technology; early adoption of newly emerging smaller, cheaper autonomous technologies; investment in local skills and support facilities to aid local buy-in and acceptance while supporting regional capacity.

Rationale & Objective The current classification system for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) does not fully capture the complex structural changes in kidney biopsies, nor the clinical and molecular heterogeneity of these diseases. Study Design Prospective observational cohort study. Setting & Participants N=221 MCD and FSGS patients enrolled in the Nephrotic Syndrome Study Network (NEPTUNE). Exposures The NEPTUNE Digital Pathology Scoring System (NDPSS) was applied to generate scores for 37 glomerular descriptors. Outcomes Time from biopsy to complete proteinuria remission, time from biopsy to kidney disease progression (40% eGFR decline or kidney failure), and eGFR over time. Analytical Approach Cluster analysis was used to group patients with similar morphologic characteristics. Glomerular descriptors and patient clusters were assessed for associations with outcomes using adjusted Cox models and linear mixed models. Messenger RNA from glomerular tissue was used to assess differentially expressed genes between clusters and identify genes associated with individual descriptors driving cluster membership. Results Three clusters were identified: X (N=56), Y (N=68), and Z (N=97). Clusters Y and Z had higher probabilities of proteinuria remission (HR [95% CI]= 1.95 [0.99, 3.85] and 3.29 [1.52, 7.13], respectively), lower hazards of disease progression 0.22 [0.08, 0.57] and 0.11 [0.03, 0.45], respectively), and lower loss of eGFR over time compared with X. Cluster X had 1920 differentially expressed genes compared to Y+Z, which reflected activation of pathways of immune response and inflammation. Six descriptors driving the clusters individually correlated with clinical outcomes and gene expression. Limitations Low prevalence of some descriptors and biopsy at a single time point. Conclusions The NDPSS allows for categorization of FSGS/MCD patients into clinically and biologically relevant subgroups, and uncovers histologic parameters associated with clinical outcomes and molecular signatures not included in current classification systems.

BACKGROUND: Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs the potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as eGFR and proteinuria, is unclear. METHODS: We performed a standardized semiquantitative histologic analysis of 859 nephrectomies obtained from individuals with or without diabetes mellitus or hypertension and varying degrees of kidney dysfunction. Changes in glomeruli, tubules, interstitium, and the vasculature were scored using 17 descriptive parameters in a standardized manner. We used multivariable linear and logistic regression analyses and unbiased, hierarchical clustering to assess associations between histologic alterations and clinical variables. RESULTS: At CKD stages 3–5, eGFR correlates reasonably well with the degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA). In patients with CKD stages 1–2, the degree of histologic damage was highly variable and eGFR poorly estimated the degree of damage. Individuals with diabetes mellitus, hypertension, or Black race had significantly more glomerulosclerosis and IFTA, at the same eGFR level. Inclusion of glomerulosclerosis improved the kidney function decline estimation, even at early disease stages. CONCLUSIONS: Histologic analysis is an important complementary method for kidney disease evaluation, especially at early disease stages. Some individuals present with relatively severe structural damage despite preserved eGFR.

PURPOSE To develop a scheme to quantitatively assess localization accuracy of tomosynthesis-guided vacuum-assisted breast biopsy apparatus. METHODS A phantom containing a metallic pellet on a flexible plastic shaft was constructed and was tested in cranio-caudal (CC) and lateral (LAT) arm biopsy geometries following the standard clinical breast biopsy workflow. Three points were manually digitized on tomosynthesis images including: the center of the target, and the tip of the needle in pre- and postfire positions. The needle trajectory was determined and four error metrics were defined: (1) stroke length error (difference between the nominal and measured stroke lengths); (2) Euclidian distance between the target and center of trough (i.e., aperture); (3) longitudinal distance between target and center of trough; and (4) lateral distance between target and needle. The proposed methodology was also evaluated on a breast gel phantom and the complete biopsy procedure, including vacuum-assisted biopsy was performed. RESULTS Three biopsy geometries were investigated: (i) LAT arm on a prone table unit (Hologic, Affirm Prone), (ii) CC- and (iii) LAT arm in an upright unit (Hologic Affirm Upright). Both biopsy units passed the vendor-provided daily localization accuracy test, with

Introduction Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood. Methods This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months. Results Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13–149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model. Conclusion The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline., Graphical abstract

Individuals with acquired cystic kidney disease (ACKD) in the setting of end-stage renal disease (ESRD) have a high risk of developing renal cell carcinoma (RCC). ACKD-RCC is considered a distinct renal neoplasm in the International Society of Urologic Pathologists (ISUP)-World Health Organization (WHO) classification of kidney tumors which may behave aggressively. Since its original description, there have been multiple case reports and series published; however, the pathogenesis of this neoplasm is uncertain and there is limited data on the genetic aberrations of this tumor. Herein, we present our experience with ESRD kidneys, with emphasis on ACKD-RCC, associated cysts, and the somatic mutation analysis of a subset of ACKD-RCCs using next-generation sequencing. Our data on 59 cases with ESRD that underwent nephrectomy, shows that ACKD-RCC represents more than half of the tumors (25/46; 54%) developing in ESRD, followed by papillary RCC (13; 28%). History of dialysis, male sex, and African American race were potential risk factors for developing ACKD-RCCs. Further, ACKD-RCC-like cysts are possible precursors of RCCs in the ACKD setting noted in 40 of 46 (87%) cases with tumors. Next-generation sequencing analysis revealed recurrent mutations in the KMT2C gene in 4 of 5 ACKD-RCCs (80%), exclusively exhibiting cribriform "sieve-like" morphology; whereas the case negative for KMT2C mutations exhibited "type 2" papillary RCC morphology and lacked "sieve-like" growth pattern. Pathogenic mutations in TSC2 were the second common abnormality (3/5; 60%), often coexisting with KMT2C mutations. Deleterious mutations in additional genes such as CBL, PDGFRA, and SYNE1, etc. were noted but were nonrecurrent and always coexisted with mutations in KMT2C or TSC2. To conclude, our study highlights that mutations in a chromatin-modifying gene KMT2C may potentially be oncogenic drivers for the development of ACKD-RCC with classic sieve-like morphology. In addition, pathogenic mutations in TSC2 possibly play a role in the development of cysts/tumors in a subset of ACKD patients. If corroborated in larger cohorts, these findings would be useful in planning surveillance and early intervention in ESRD patients developing ACKD.

Diabetic kidney disease (DKD) accounts for nearly half of all CKD in the United States. The diagnosis of DKD is usually made clinically, on the basis of longstanding (>5 years) diabetes or concurrent microvascular complications, and the presence of albuminuria and/or decreased eGFR. The

Pretreatment determination of renal cell carcinoma aggressiveness may help to guide clinical decision-making. Purpose To evaluate the efficacy of residual convolutional neural network using routine MRI in differentiating low-grade (grade I-II) from high-grade (grade III-IV) in stage I and II renal cell carcinoma. Study type Retrospective. Population In all, 376 patients with 430 renal cell carcinoma lesions from 2008-2019 in a multicenter cohort were acquired. The 353 Fuhrman-graded renal cell carcinomas were divided into a training, validation, and test set with a 7:2:1 split. The 77 WHO/ISUP graded renal cell carcinomas were used as a separate WHO/ISUP test set. Field strength/sequence 1.5T and 3.0T/T2 -weighted and T1 contrast-enhanced sequences. Assessment The accuracy, sensitivity, and specificity of the final model were assessed. The receiver operating characteristic (ROC) curve and precision-recall curve were plotted to measure the performance of the binary classifier. A confusion matrix was drawn to show the true positive, true negative, false positive, and false negative of the model. Statistical tests Mann-Whitney U-test for continuous data and the chi-square test or Fisher's exact test for categorical data were used to compare the difference of clinicopathologic characteristics between the low- and high-grade groups. The adjusted Wald method was used to calculate the 95% confidence interval (CI) of accuracy, sensitivity, and specificity. Results The final deep-learning model achieved a test accuracy of 0.88 (95% CI: 0.73-0.96), sensitivity of 0.89 (95% CI: 0.74-0.96), and specificity of 0.88 (95% CI: 0.73-0.96) in the Fuhrman test set and a test accuracy of 0.83 (95% CI: 0.73-0.90), sensitivity of 0.92 (95% CI: 0.84-0.97), and specificity of 0.78 (95% CI: 0.68-0.86) in the WHO/ISUP test set. Data conclusion Deep learning can noninvasively predict the histological grade of stage I and II renal cell carcinoma using conventional MRI in a multiinstitutional dataset with high accuracy. Level of evidence 3 TECHNICAL EFFICACY STAGE: 2.

The purpose of this study is to provide a more accurate estimation of the radiation dose of contrast-enhanced spectral mammography (CESM) relative to that of 2D digital mammography and tomosynthesis using phantom and patient data and an accepted dosimetry protocol that eliminates vendor-specific average glandular dose (AGD) estimates while including breast density.Patient and phantom AGD estimation was performed using two vendors (system 1 and system 2) in five imaging modes, including 2D, 3D, and CESM imaging. Patient AGD was retrospectively estimated from 45 patients who underwent mammography with all imaging modes during 2012-2016. Patient and phantom AGD were estimated using accepted European and International Atomic Energy Agency protocols for dosimetry and were compared across imaging modes using a paired t test with Bonferroni correction.Phantom data showed that the imaging modes with the lowest to highest AGDs were system 1 2D, followed by system 2 2D and system 2 3D, which had comparable values (p = 0.6), followed by system 1 CESM, and then by system 2 2D plus 3D. One hundred eighty views in 45 patients showed that the system 1 CESM AGD was 1.8 times greater than the system 1 2D AGD (p0.001), 1.2 times greater than the system 2 2D AGD (p0.001), 1.2 times greater than the system 2 3D AGD (p0.001), and 0.6 times less than the system 2 2D plus 3D AGD (p0.001).The CESM dose for system 1 is within an acceptable range as compared with other commonly performed mammographic examinations and should not preclude its use as a diagnostic breast imaging tool.

Social scientists and science communicators are concerned about the apparent discrepancy between the scientific consensus on climate change (Anderegg et al. Proc Natl Acad Sci 107:12107–12109, 2010; Doran and Zimmerman EOS Trans Am Geophys Union 90:22–3, 2009) and the general public’s views (Knight Environ Sociol 2:101–113, 2016; Lee et al. Nat Clim Chang 5:1014–1020, 2015). It is reasoned that increased public awareness and perceived threat of climate change may pressure governments to enact policy to counteract climate change (e.g. setting stringent carbon emissions targets). Despite a logical link between public awareness and government-set emissions targets, this relationship remains untested. We examined the relationship between public awareness about and perceived threat of climate change and governmental emissions targets across 71 countries and 1 region. We found a positive association between the proportions of a country’s population that are aware of climate change and the unconditional emissions reduction targets set by that country in the Paris Agreement (Rogelj et al. Nature 534:631–639, 2016). However, the proportion of people in a country who perceive climate change as a personal threat was not associated with higher emissions reduction targets. Our results suggest that public awareness may be an important part of garnering the public support required for policies designed to mitigate climate change to succeed.

The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy.

This study determined whether mild dehydration influenced skeletal muscle glycogen use, core temperature or performance during high-intensity, intermittent cycle-based exercise in ice hockey players vs. staying hydrated with water. Eight males (21.6 ± 0.4 yr, 183.5 ± 1.6 cm, 83.9 ± 3.7 kg, 50.2 ± 1.9 ml·kg-1·min-1) performed two trials separated by 7 days. The protocol consisted of 3 periods (P) containing 10 × 45-s cycling bouts at ~133% VO2max, followed by 135 s of passive rest. Subjects drank no fluid and dehydrated during the protocol (NF), or maintained body mass by drinking WATER. Muscle biopsies were taken at rest, immediately before and after P3. Subjects were mildly dehydrated (-1.8% BM) at the end of P3 in the NF trial. There were no differences between the NF and WATER trials for glycogen use (P1+P2; 350.1 ± 31.9 vs. 413.2 ± 33.2, P3; 103.5 ± 16.2 vs. 131.5 ± 18.9 mmol·kg dm-1), core temperature (P1; 37.8 ± 0.1 vs. 37.7 ± 0.1, P2; 38.2 ± 0.1 vs. 38.1 ± 0.1, P3; 38.3 ± 0.1 vs. 38.2 ± 0.1 °C) or performance (P1; 156.3 ± 7.8 vs. 154.4 ± 8.2, P2; 150.5 ± 7.8 vs. 152.4 ± 8.3, P3; 144.1 ± 8.7 vs. 148.4 ± 8.7 kJ). This study demonstrated that typical dehydration experienced by ice hockey players (~1.8% BM loss), did not affect glycogen use, core temperature, or voluntary performance vs. staying hydrated by ingesting water during a cycle-based simulation of ice hockey exercise in a laboratory environment.

Introduction Financial incentive (FI) programmes can promote smoking cessation. While foundational research suggests higher FI amounts may better produce outcomes, confirmation is needed. Further, the optimal amount(s) needed to cost-effectively promote change is unclear. Our objective was to reconfirm whether higher amounts are associated with greater quitting through review of previous programmes, before assessing whether non-linear trends and obvious inflections in this relationship exist which may highlight optimal amounts. Methods Four databases were searched for controlled or randomised controlled studies which detailed FI programmes for smoking cessation in adults. Results Twenty-six studies were included. Programmes varied in length (3.0–52.0 weeks, median = 12.0), FI provision timing, and longest follow-up (5.5–24.0 months, median = 6.0). The odds ratio of quitting at longest follow-up ranged from 0.32 to 5.89. Maximum FI amounts were between US$106.19 and $4,027.92. Quit rates and amounts were not significantly correlated. Subsequent comparisons to reduce between-study variations were non-significant. Further analyses revealed no evidence of non-linear fits, changes in inflection, or cut-points. Conclusions While higher FI amounts were not associated with greater quitting within this review, the limited data available and variations in target populations and programme designs unrelated to the amount have undoubtedly influenced results. Findings suggest information on this relationship and optimal FI amounts are not determinable through current evidence. As this information is important for cost-effectiveness evaluations and real-world viability, further investigation is necessary. Laboratory research could provide valuable initial insight. Trials comparing programme efficacy under the identified amounts could then be implemented.

PURPOSE Water equivalent diameter (WED) is a robust patient-size descriptor. Localizer-based WED estimation is less sensitive to truncation errors resulting from limited field of view, and produces WED estimates at different locations within one localizer radiograph, prior to the initiation of axial scans. This method is considered difficult to implement by the clinical community due to the necessary calibration between localizer pixel values (LPV) and attenuation, and the unknown stability of calibration results across scanners and over time. We investigated the stability of calibration results across 25 computed tomography (CT) scanners from three medical centers, and their stability over 3 ∼ 29 months for 14 of those scanners. METHODS Localizer and axial images of ACR and body computed tomography dose index phantoms were acquired, using routine clinical techniques (120 kV and lateral localizers) on each of the 25 CT scanners: 8 GE scanners (CT750HD, VCT, and Revolution), 8 Siemens scanners (Definition AS, Force, Flash, and Edge), 5 Canon scanners (Aquilion-One, Aquilion-Prime80, and Aquilion-64), and 4 Philips scanners (iCT 256, iQon, and Ingenuity). By associating axial images with the corresponding localizer lines, the relationship between the scaled water equivalent area (WEA) and averaged LPV were established through regression analysis. RESULTS Linear relationships between the scaled WEA and the averaged LPV were observed in all 25 CT scanners ( R2>0.999 ). Calibration parameters were similar for CT scanners from the same vendor: the coefficients of variation (COV) were ≤ 1% in all four vendor groups for the calibration slope, and

Climate change and variability are major societal challenges, and the ocean is an integral part of this complex and variable system. Key to the understanding of the ocean's role in the Earth's climate system is the study of ocean and sea-ice physical processes, including its interactions with the atmosphere, cryosphere, land and biosphere. These processes include those linked to ocean circulation; the storage and redistribution of heat, carbon, salt and other water properties; and air-sea exchanges of heat, momentum, freshwater, carbon and other gasses. Measurements of ocean physics variables are fundamental to reliable earth prediction systems for a range of applications and users. In addition, knowledge of the physical environment is fundamental to growing understanding of the ocean's biogeochemistry and biological/ecosystem variability and function. Through the progress from OceanObs'99 to OceanObs'09, the ocean observing system has evolved from a platform centric perspective to an integrated observing system. The challenge now is for the observing system to evolve to respond to an increasingly diverse end user group. The Ocean Observations Physics and Climate panel (OOPC), formed in 1995, has undertaken many activities that led to observing system-related agreements. Here, OOPC will explore the opportunities and challenges for the development of a fit-for-purpose, sustained and prioritized ocean observing system, focusing on physical variables that maximize support for fundamental research, climate monitoring, forecasting on different timescales, and society. OOPC recommendations are guided by the Framework for Ocean Observing (Lindstrom et al. 2012) which emphasizes identifying user requirements by considering time and space scales of the Essential Ocean Variables. This approach provides a framework for reviewing the adequacy of the observing system, looking for synergies in delivering an integrated observing system for a range of applications and focusing innovation in areas where existing technologies do not meet these requirements. Fil: Sloyan, Bernadette M.. Csiro Oceans and Atmosphere; Australia Fil: Wilkin, John. State University of New Jersey; Estados Unidos Fil: Hill, Katherine L.. World Meteorological Organization; Suiza Fil: Chidichimo, María Paz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Instituto Franco-argentino sobre Estudios del Clima y sus Impactos; Argentina Fil: Cronin, Meghan F.. National Oceanic and Atmospheric Administration; Estados Unidos Fil: Johannessen, Johnny A.. University of Bergen; Noruega Fil: Karstensen, Johannes. Geomar-Helmholtz Centre for Ocean Research Kiel; Alemania Fil: Krug, Marjolaine. Council for Scientific and Industrial Research; Sudáfrica Fil: Lee, Tong. National Aeronautics and Space Administration; Estados Unidos Fil: Oka, Eitarou. The University of Tokyo; Japón Fil: Palmer, Matthew D.. Met Office Hadley Centre; Reino Unido Fil: Rabe, Benjamin. Alfred-Wegener-Institut. Helmholtz-Zentrum für Polar und Meeresforschung; Alemania Fil: Speich, Sabrina. Ecole Normale Supérieure; Francia Fil: Von Schuckmann, Karina. Mercator Ocean International; Francia Fil: Weller, Robert A.. Woods Hole Oceanographic Institution; Estados Unidos Fil: Yu, Weidong. National Marine Environmental Forecasting Center; China

Several previous studies have reported performance decrements in team sport athletes who dehydrated approximately 1.5–2% of their body mass (BM) through sweating. This study measured on-ice sweat loss, fluid intake, sodium balance, and carbohydrate (CHO) intake of 77 major junior (JR; 19 ± 1 years), 60 American Hockey League (AHL; 24 ± 4 years), and 77 National Hockey League (NHL; 27 ± 5 years) players. Sweat loss was calculated from pre- to post-exercise BM plus fluid intake minus urine loss. AHL (2.03 ± 0.62 L/hr) and NHL (2.02 ± 0.74 L/hr) players had higher sweat rates (p p = .006) and NHL (1.29% ± 0.63%; p p > .05). Sodium deficits (sodium loss − intake) were greater (p 2% BM) during 60 min of practice. However, ∼15%, 41%, and 48% of the JR, AHL, and NHL players, respectively, may have reached mild dehydration and increased risk of performance decrements in a 90-min practice.

The effects of menstrual phase on athletic performance are controversial, but commonly ascribed to temperature-related impairments in physical and cognitive performances. Caffeine stimulates the CN...

Background Pediatric cancer patients requiring radiation therapy (RT) have been routinely assessed and referred to proton therapy (PT) at an external institution. The benefit of the delivered PT compared to the state-of-the-art intensity modulated x-ray RT (XT) at the home institution was evaluated. Procedure Twenty-four consecutive children referred for PT during 2010–2013 for craniospinal (CSI, n = 10), localized intracranial (IC, n = 7), head/neck (HN, n = 4) or parameningeal (PM, n = 3) lesions were included. The median age was 8 years (2–16 years). XT plans were generated for each patient, blinded to the PT delivered. Dosimetry, estimated growth hormone deficiency (GHD), and neurocognitive dysfunction (NCD) risks were compared for PT and XT (Wilcoxon). Results PT started (median) 5 weeks (± 1.3 weeks, 95% CI) after referral. For CSI patients, PT was clearly superior to XT plans with median dose reductions for the heart, lungs and thyroid of 17, 2.5 and 18 Gy, respectively (P = 0.005). The median estimated NCD and GHD risks were 1–3 (max 16) and 2 (max 61) percentage points, respectively, lower for PT compared to XT. The median of the mean doses to the brain, cochleae and pituitary gland was lower with PT than XT for the IC, H/N and PM patients (P

Temperature and current measurements from two moorings onshore of the Celtic Sea shelf break, a well-known hot spot for tidal energy conversion, show the impact of passing summer storms on the baroclinic wavefield. Wind-driven vertical mixing changed stratification to permit an increased on-shelf energy transport, and baroclinic energy in the semidiurnal band appeared at the moorings 1–4 days after the storm mixed the upper 50 m of the water column. The timing of the maximum in the baroclinic energy flux is consistent with the propagation of the semidiurnal internal tide from generation sites at the shelf break to the moorings 40 km away. Also, the ∼3 day duration of the peak in M2 baroclinic energy flux at the moorings corresponds to the restratification time scale following the first storm.

Background: It has been suggested that platelet-rich plasma (PRP) improves healing after arthroscopic rotator cuff repair. The current literature provides ample but inconsistent data on this topic. Purpose: To systematically review the current in vivo evidence for the use of platelet concentrates (PRP) in the arthroscopic treatment of rotator cuff tears to assess effectiveness, safety, and cost-effectiveness. Study Design: Meta-analysis and cost-effectiveness analysis. Methods: Published evidence from controlled, human trials of rotator cuff repair augmented with platelet concentrates was systematically gathered, and data on retear rates were extracted. Mathematical and clinical heterogeneity was evaluated, and fixed-effect meta-analysis was performed to calculate the risk ratio (RR) of retears and the number needed to treat (NNT). Subgroup analyses were made for small/medium tears (n = 404) and large/massive tears (n = 374). Cost-effectiveness was assessed using data from this meta-analysis and using cost data from the literature, including extensive sensitivity analyses, to calculate the incremental cost-effectiveness ratio (ICER). Results: Thirteen studies published between 2010 and 2014 were identified for analysis. The RR for retear for all patients was 0.87 (95% CI, 0.67-1.12; P = .286). For small- and medium-sized tears (Conclusion: In large tears, even with double-row repair, the beneficial effects of PRP alone are insufficient to compensate the progressed tissue damage. The study data suggest that PRP may promote healing of small- and medium-sized tears to reduce retear rates. However, despite the substantial biological effect, at current cost, the use of PRP is not cost-effective in arthroscopic repair of small- and medium-sized tears.

Posttraumatic Stress Disorder (PTSD) is associated with elevated noradrenergic signaling, which has an impact on emotional learning and memory. Fear extinction is thought to underlie the processes of exposure therapy, however the relationship between noradrenaline and extinction in PTSD is unclear. Participants with PTSD (n = 21), trauma-exposure without PTSD (TC; n = 36), and non-trauma-exposed controls (NTC; n = 27) completed a fear conditioning and extinction paradigm, and conditioned fear was indexed by skin conductance response (SCR). Salivary α-amylase (sAA) collected at baseline and immediately post-fear acquisition was used as an index of noradrenaline, and we examined whether sAA in response to fear acquisition was a moderator between fear extinction and PTSD symptoms. While there was a significant increase in sAA from baseline to post-fear acquisition, this was not modulated by group. Compared to TC and NTC, the PTSD group displayed a slower decline in SCRs during early extinction, which generalized across stimulus type, and was not moderated by sAA. These findings suggest that the relationship between fear extinction and PTSD symptoms does not change as a function of sAA levels; however previous research suggests other processes of fear learning may be associated with noradrenergic activity in PTSD.

To better anticipate potential impacts of climate change, diverse information about the future is required, including climate, society and economy, and adaptation and mitigation. To address this need, a global RCP (Representative Concentration Pathways), SSP (Shared Socio-economic Pathways), and SPA (Shared climate Policy Assumptions) (RCP SSP SPA) scenario framework has been developed by the Intergovernmental Panel on Climate Change Fifth Assessment Report (IPCC-AR5). Application of this full global framework at sub-national scales introduces two key challenges: added complexity in capturing the multiple dimensions of change, and issues of scale. Perhaps for this reason, there are few such applications of this new framework. Here, we present an integrated multi-scale hybrid scenario approach that combines both expert-based and participatory methods. The framework has been developed and applied within the DECCMA 1 project with the purpose of exploring migration and adaptation in three deltas across West Africa and South Asia: (i) the Volta delta (Ghana), (ii) the Mahanadi delta (India), and (iii) the Ganges-Brahmaputra-Meghna (GBM) delta (Bangladesh/India). Using a climate scenario that encompasses a wide range of impacts (RCP8.5) combined with three SSP-based socio-economic scenarios (SSP2, SSP3, SSP5), we generate highly divergent and challenging scenario contexts across multiple scales against which robustness of the human and natural systems within the deltas are tested. In addition, we consider four distinct adaptation policy trajectories: Minimum intervention, Economic capacity expansion, System efficiency enhancement, and System restructuring, which describe alternative future bundles of adaptation actions/measures under different socio-economic trajectories. The paper highlights the importance of multi-scale (combined top-down and bottom-up) and participatory (joint expert-stakeholder) scenario methods for addressing uncertainty in adaptation decision-making. The framework facilitates improved integrated assessments of the potential impacts and plausible adaptation policy choices (including migration) under uncertain future changing conditions. The concept, methods, and processes presented are transferable to other sub-national socio-ecological settings with multi-scale challenges. © 2018 This work is carried out under the Deltas, Vulnerability & Climate Change: Migration & Adaptation (DECCMA) project (IDRC 107642) under the Collaborative Adaptation Research Initiative in Africa and Asia (CARIAA) programme with financial support from the UK Government's Department for International Development (DFID) and the International Development Research Centre (IDRC 1076422 ), Canada.

Fear reinstatement is one of several paradigms designed to measure fear return following extinction, as a laboratory model for the relapse of Posttraumatic Stress Disorder (PTSD) symptoms. Sleep is a key factor in emotional memory consolidation, and here we examined the relationship between sleep quality and fear reinstatement in PTSD, relative to trauma-exposed and non-exposed controls. The Pittsburgh Sleep Quality Index (PSQI) was used as a subjective measure of sleep quality, and skin conductance responses (SCR) and unconditioned stimulus (US)-expectancy ratings were used to index threat responses during a differential fear conditioning, extinction, and reinstatement paradigm. There were no significant between-group differences in the reinstatement of conditioned responding. Sleep disturbance and sleep onset latency were significant moderators between reinstatement of fear and PTSD symptom severity, such that there was a positive relationship between PTSD symptoms and fear reinstatement for higher levels - but not lower levels - of sleep disturbance and sleep onset latency. To our knowledge, this is the first study to investigate PTSD-specific reinstatement patterns and sleep as a boundary condition of reinstatement. Future research using polysomnographic measures of sleep-wave architecture may further clarify the relationship between fear reinstatement and sleep quality in clinical samples with PTSD relative to controls.

This study determined whether ingesting a carbohydrate-electrolyte solution (CES) vs. progressive dehydration affected skeletal muscle glycogen use and performance in ice hockey players during simulated ice hockey exercise comprised of 3 active “periods”. Seven males (21.3±0.3 years, 184.7±1.2 cm, 84.2±3.9 kg, and 49.6±1.8 mL·kg−1·min−1) performed a hockey-specific protocol on two occasions and either dehydrated progressively (NF), or stayed well-hydrated by ingesting a CES. Muscle biopsies were taken at rest, before the 3rd period (P3), and after the final sprint in the protocol. Compared to dehydration in the NF trial (−1.8% BM), CES ingestion enhanced voluntary performance (151.0±8.0 vs. 144.1±8.7 kJ) and glycogen use (177.5±31.1 vs. 103.5±16.2 mmol·kg dm−1), and reduced perceived exertion (16±1 vs. 18±1) in P3. Mean core temperature was reduced by CES ingestion throughout the protocol (38.0±0.2 vs. 38.1±0.1°C). These results suggest that compared to progressive dehydration, staying hydrated by ingesting a CES helps preserve performance, while reducing thermal and perceptual strains, in P3 of cycle-based simulation of ice hockey exercise. These benefits are observed despite greater glycogen use in P3 with CES ingestion.

Despite numerous innovative studies, rates of replication in the field of music psychology are extremely low (Frieler et al., 2013). Two key methodological challenges affecting researchers wishing to administer and reproduce studies in music cognition are the difficulty of measuring musical responses, particularly when conducting free-recall studies, and access to a reliable set of novel stimuli unrestricted by copyright or licensing issues. In this article, we propose a solution for these challenges in computer-based administration. We present a computer-based application for testing memory for melodies. Created using the software Max/MSP (Cycling '74, 2014a), the MUSOS (Music Software System) Toolkit uses a simple modular framework configurable for testing common paradigms such as recall, old-new recognition, and stem completion. The program is accompanied by a stimulus set of 156 novel, copyright-free melodies, in audio and Max/MSP file formats. Two pilot tests were conducted to establish the properties of the accompanying stimulus set that are relevant to music cognition and general memory research. By using this software, a researcher without specialist musical training may administer and accurately measure responses from common paradigms used in the study of memory for music.

Introduction:Results from observational studies suggest that smoking-related cues play a role in triggering relapse. Coping strategies are among the most commonly used cessation strategies, but little is known about how they aid quitting.Aims:The aim of this pilot study was to evaluate the effect of a suite of selected coping techniques on alleviating cue-induced cravings.Methods:Thirty-seven daily smokers (Intervention: 20; Control: 17) participated in two laboratory cue-reactivity sessions, separated by approximately one week, during which craving was assessed before and after exposure to smoking-related cues. Following the first session, participants in the Intervention Group were taught a suite of coping strategies. During the second session, participants in the Intervention Group were encouraged to use these strategies.Results:Participants in the Intervention Group reported a slight decrease in craving following the acute exposure manipulation at the second session, compared to an increase in craving among participants in the Control Group. Intervention Group participants also reported a decrease in craving following prolonged exposure to the smoking cues (compared to an increase in craving among Control Group participants). In both cases, the difference between groups was more pronounced among smokers who responded to the cue-reactivity manipulation. The observed differences were not significant.Conclusions:The results of this pilot study suggest that coping techniques may be beneficial in alleviating both the initial spike in craving observed following acute cue exposure, and aid recovery during prolonged exposure. These findings need to be replicated in a larger study.

We present the case of a 49-year-old man with an 18-month history of an intermittently pruritic red-brown reticulate eruption of the medial legs, with occasional blistering. There were areas of scale, crust and superficial erosions. The patient worked long overnight shifts standing in front of hot machinery wearing shorts, and spent time sitting in front of a heater at home. A clinical diagnosis of erythema ab igne (EAI) was made. This settled with heater avoidance and protection of the legs with long trousers, as well as a topical corticosteroid. Histology showed features of cutaneous reactive angiomatosis, a rare condition with various associations but only previously reported once in association with EAI.

The aim of this study was to assess the volume and function of human brown adipose tissue (BAT) in vivo using MR imaging.BAT volumes under thermoneutral conditions in the cervical areas were assessed via water-fat contrast using the Dixon method and via water-saturation efficiency using fast spin-echo and T2-weighted images. The existence of cervical BAT was also assessed by (18)F-FDG PET/CT scans in the same subjects. BAT functionality was assessed via functional MR imaging (fMRI) blood oxygenation level-dependent (BOLD) signal changes in response to a mild cold challenge.Under thermoneutral conditions, we were able to distinguish BAT from white adipose tissue in the cervical and supraclavicular fat. BAT showed higher water-to-fat contrast and higher water-saturation efficiency in MR imaging scans. The location and volume of BAT assessed by MR imaging were comparable to the measurements by (18)F-FDG PET/CT scans. During mild cold challenge, BOLD fMRI signal increased in BAT by 10.7% ± 1.8% (P0.01).We demonstrated the feasibility of using MR imaging and fMRI to assess BAT volume and BAT responses to mild cold stimulation in the cervical areas of human subjects.

PURPOSE: The use of reirradiation for recurrent pediatric brain tumors has been increasing, but the effect of repeat radiation on critical cranial structures is unknown. METHODS AND MATERIALS: Between July 2009 and May 2013, the records of 12 pediatric patients initially treated with proton therapy and then with reirradiation for recurrent brain tumors were retrospectively reviewed for toxicity and outcomes. Initial and repeat radiation dose distributions were deformed and merged to determine the maximum dose to 0.03 cm(3) of the optic chiasm, optic nerves, spinal cord, brainstem, cochleae, pituitary, and uninvolved brain, and to 1 cm(3) of the brainstem and brain on individual and composite plans. These dosimetric results were compared with auditory, neurocognitive, ophthalmologic, and endocrine outcomes to identify radiation-associated toxicities. RESULTS: Median follow-up was 3.5 years from diagnosis. Median ages at initial and repeat radiation were 4.6 and 6.7 years, respectively. All patients initially received proton radiotherapy to a median tumor dose of 55.8 Gy relative biological effectiveness (RBE) (range, 45 to 60 Gy [RBE]). At progression, patients completed a second course of radiation to local fields (n = 7) or the craniospinal axis (n = 5) with a median tumor dose of 40 Gy (RBE) (range, 20 to 54 Gy [RBE]). Median progression-free survival was 22.7 months from the last day of the second radiation course. No patient developed central nervous system necrosis requiring treatment. Of evaluable patients, none developed radiation-related high-grade hearing loss (n = 11), visual pathway deficit (n = 10), or significant change in pre- and post-reirradiation full-scale intelligence quotient (n = 4). Of 11 evaluable patients, 4 (36.4%) developed secondary hypothyroidism and 1 (9.1%) developed growth hormone deficiency. CONCLUSION: Repeat radiation for recurrent brain tumors after proton therapy may be performed in the pediatric population with acceptable short- and long-term toxicity.

Purpose To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas, and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1–3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7–51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.

Purpose Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center. Methods and Materials This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log–rank test. Results The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38–86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36–57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%–1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log–rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups. Conclusions This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical outcomes are encouraging. Prospective comparison with more traditional approach is warranted.

Aim Physiologic activity of 18F-fluorodeoxyglucose (FDG) in the intestinal tract occurs frequently in patients undergoing PET/computed tomography (CT) imaging, appearing most often in the colon. The purpose of this study is to determine the localization of the FDG within the colon. We hypothesize that intestinal FDG activity is intraluminal. Methods In a prospective Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, patients with physiologic colonic FDG activity on PET/CT scans were enrolled to undergo repeat imaging 2 h after stimulation of colonic motility with a high-fat meal. Results We identified 13 patients who had focal FDG activity in their colon during a routine clinical PET/CT scan. After administration of a high-fat meal, 10 patients (77%) demonstrated antegrade movement of FDG along the colon, consistent with luminal clearance. Conclusion Our results suggest that normal physiologic FDG activity within the large intestine, seen on PET/CT scans, is intraluminal.

The purpose of this study was to evaluate the number of segments per beam for intensity-modulated radiation therapy (IMRT) treatments and its effects on the plan quality, treatment delivery time, machine quality assurance, and machine maintenance. We have retrospectively analyzed 24 patients treated with IMRT. Five were selected within each of the following regions: head and neck, thoracic, abdomen, and prostate. Four patients were optimized within the brain region. The clinically treated plans were re-optimized using Philips Pinnacle3 v. 8 with the direct machine parameter optimization algorithm. The number of segments per beam from the treated plan was systematically reduced by 80%, 60%, 40%, and 30%, and the following statistics have been analyzed for plan quality: target min, mean, and max doses; critical structure doses; and integral dose. We have attempted to define the smallest number of segments per beam for IMRT treatment plans. Results indicate that IMRT plans can be delivered with acceptable quality with approximately 3–6 segments per beam for the anatomical regions analyzed. A reduction in the number of segments decreases treatment delivery time, reduces machine wear and tear, and minimizes the amount of time the patient is on the treatment table, which in turn reduces the chances of intrafractional uncertainties.

Purpose Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose–volume histograms. Results The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3% ∗ ), dentate gyrus (27.3, 75.0% ∗ ), and subventricular zone (4.5, 57.8% ∗ ). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3 ∗ , 100.0% ∗ ; middle cerebral arteries, 25.9% ∗ , 100% ∗ ; anterior communicating arteries, 30.8 ∗ , 41.7% ∗ ; and carotid arteries, 51.5 ∗ , 77.6 ∗ ). Relative reduction of integral dose to the infratentorial brain (190.7 ∗ , 109.7% ∗ ), supratentorial brain without PTV (9.6, 26.8% ∗ ), brainstem (45.6, 22.4% ∗ ), and whole brain without PTV (19.4 ∗ , 34.4% ∗ ) were recorded with the use of proton therapy. ( ∗ Differences were significant based on Friedman's test with Bonferroni-Dunn correction, α = 0.05) Conclusions The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.

Radiation for carcinoma of the distal esophagus is associated with cardiac perfusion deficits and pericardial effusion. We performed a dosimetric analysis of alternative beam arrangements for use in intensity modulated radiation therapy (IMRT) planning, seeking to lower radiation dose to the heart.Treatment plans using 4 separate beam arrangements were generated and optimized for 12 patients. Hemispheric and butterfly beam arrangements were compared with plans with posterior and lateral beam entries. Radiotherapy was planned to 50.4 Gy in 28 fractions, using step and shoot IMRT with 6 MV photons. Mean heart dose and volumes of heart and lung receiving up to specified doses (V5-V40) were recorded. Isodose distributions were evaluated for target coverage and normal tissue exposure.IMRT plans utilizing posterior-lateral beam arrangements significantly reduced mean cardiac doses (32.5 ± 3.9 Gy, 33.3 ± 3.2 Gy vs 24.3 ± 3.7 Gy, and 23.4 ± 4.2 Gy, P.05, paired Student t test with post hoc Bonferroni correction) as well as the total heart volumes receiving at least 20 and 30 Gy. IMRT allowed the maximum cord dose to be limited to less than 40 Gy. While both posterior-lateral beam arrangements lead to improved cardiac dosimetry, mean lung doses as well as V5 and V20 were slightly higher, although within accepted limits. Target coverage, homogeneity, and conformality were similar or improved with the use of alternative beam configurations.The use of IMRT with posterior-lateral beams can significantly reduce radiation dose to cardiac structures with minimal increased dose to the lung. Future studies will assess the physiologic and clinical impact of cardiac sparing.