Std Err Research Articles

An intracerebral microdialysis study to determine the neuropharmacokinetics of eribulin in patients with metastatic or primary brain tumors.

Eribulin is an inhibitor of microtubule dynamics. It is not as highly protein bound as the taxanes and is less vulnerable to extrusion by P-glycoprotein in the blood-brain barrier (BBB). These features predict that eribulin could play an active role in managing brain tumors. Indeed, the small amount of published clinical data indicates eribulin may have some efficacy against breast cancer brain metastases. To better understand the potential of eribulin for treating brain tumors, we performed an intracerebral microdialysis study to determine the neuropharmacokinetics of eribulin in cancer patients undergoing tumor resection. After tumor removal, two microdialysis catheters were inserted into peritumoral brain tissue. Approximately 24h after surgery, a single dose of eribulin 1.4mg/m2 was administered intravenously. Dialysate samples were collected continuously for 72h, with plasma samples collected in parallel. Eribulin concentrations were analyzed by tandem mass spectrometry. Dialysate samples from 12 intracerebral microdialysis catheters placed in 7 study participants were included in the analysis. A statistically significant difference was observed between eribulin concentrations in brain tissue where BBB was disrupted versus intact, with a difference in mean maximum concentrations on log2 scale of 3.37 (std err = 0.59, p-value = 0.005). Nonetheless, overall brain to plasma ratios of eribulin only ranged from 0.13 to 1.99%. Although we could detect higher concentrations of eribulin in brain tissue where BBB was disrupted, intracerebral eribulin levels were not sufficient to predict eribulin would have consistent clinically meaningful activity against tumors in the brain. NCT02338037 (January 9, 2015).

Soil carbon stocks in temperate grasslands reach equilibrium with grazing duration

Lost soil organic carbon (SOC) in degraded grasslands can be restored via the ‘grazing exclusion’ practice, but it was unknown how long (# of years) the restoration process can take. A synthesis of four decades of studies revealed that grazing exclusion increased SOC stocks in the topsoil (0–0.30 m) by 14.8 % (±0.8 Std Err), on average, compared to moderate-to-heavy grazing (MtH); During which SOC stock increased steadily, peaked in Year 18.5, and then declined. At peak, SOC stock was 42.5 % greater under grazing exclusion than under MtH due to 100.4 ± 4.2 % increase in aboveground biomass and 80.3 ± 33.5 % increase in root biomass. Grazing exclusion also increased soil C:N ratio by 7.6 % while decreasing bulk density by 9.4 %. Grazing exclusion could be ceased 18.5 years after initiation of grazing exclusion as plant biomass input balances carbon decomposition and SOC equilibrium occurs then additional benefits start diminishing.

Proof of concept for multiplex amplicon sequencing for mutation identification using the MinION nanopore sequencer

Rapid, cost-effective identification of genetic variants in small candidate genomic regions remains a challenge, particularly for less well equipped or lower throughput laboratories. The application of Oxford Nanopore Technologies’ MinION sequencer has the potential to fulfil this requirement. We demonstrate a proof of concept for a multiplexing assay that pools PCR amplicons for MinION sequencing to enable sequencing of multiple templates from multiple individuals, which could be applied to gene-targeted diagnostics. A combined strategy of barcoding and sample pooling was developed for simultaneous multiplex MinION sequencing of 100 PCR amplicons. The amplicons are family-specific, spanning a total of 30 loci in DNA isolated from 82 human neurodevelopmental cases and family members. The target regions were chosen for further interrogation because a potentially disease-causative variant had been identified in affected individuals following Illumina exome sequencing. The pooled MinION sequences were deconvoluted by aligning to custom references using the minimap2 aligner software. Our multiplexing approach produced an interpretable and expected sequence from 29 of the 30 targeted genetic loci. The sequence variant which was not correctly resolved in the MinION sequence was adjacent to a five nucleotide homopolymer. It is already known that homopolymers present a resolution problem with the MinION approach. Interestingly despite equimolar quantities of PCR amplicon pooled for sequencing, significant variation in the depth of coverage (127×–19,626×; mean = 8321×, std err = 452.99) was observed. We observed independent relationships between depth of coverage and target length, and depth of coverage and GC content. These relationships demonstrate biases of the MinION sequencer for longer templates and those with lower GC content. We demonstrate an efficient approach for variant discovery or confirmation from short DNA templates using the MinION sequencing device. With less than 130 × depth of coverage required for accurate genotyping, the methodology described here allows for rapid highly multiplexed targeted sequencing of large numbers of samples in a minimally equipped laboratory with a potential cost as much 200 × less than that from Sanger sequencing.

Left Ventricular Cardiac Dysfunction in the Diaphragmatic Hernia Fetus: Fetal Phenotypic Improvement Is Seen with Tracheal Occlusion

Background: Recent reports in the care of congenital diaphragmatic hernia (DH) patients focus on the role of decreased left ventricular cardiac output after birth. However, little is known about cardiac function while fetal physiology is still in effect, and even less is understood about the effect of fetal tracheal occlusion (TO) on the left ventricle (LV). Methods: DH were surgically created in fetal sheep at gestational age 70-76 days. Fetuses were cesarean delivered at ∼120 days gestational age, cannulated via the umbilical vein and arteries, and placed on the Extrauterine Environment for Neonatal Development (EXTEND) device. The TO device was applied for ten days, followed by a four-day recovery period of non-occlusion. Results: In the Normal group, the mean right ventricle (RV) to LV Ratio was 1.41 (Std Err 0.0098, 95% CI 1.39-1.43) on day 0 of the experiment and remained stable at 1.39 on Day 14 (Std Err 0.01, 95% CI 1.93-2.22). In the DH group, the RV to LV Ratio was mildly elevated from Day 0, at 1.47 (Std Err 0.28, 95% CI 1.08-1.82), and increased to 2.08 (Std Err 0.07, 95% CI 1.93-2.22) by Day 11 of the study. In DH with TO, the RV to LV Ratio mimicked that of the Normal group. Once TO was released, the RV to LV Ratio began to increase. Combined cardiac output (CO) was lower in the DH group. RVCO was equivalent in both groups. While LVCO remained constant in the Normal and TO groups, it dropped rapidly in the DH group (Prob>F 0.000). Conclusion: Here we demonstrate that LV dysfunction is present during fetal development in a lamb model of severe DH, and is improved by TO treatment in the EXTEND environment.RV to LV Ratio in Fetal Lambs on EXTENDIn DH with TO, the RV to LV Ratio mimicked that of the Normal group. Once TO was released, the RV to LV Ratio began to increase. Here, you see an increase in the RV to LV ratio with balloon release. As a result of the balloon release, the RV to LV ratio begins to drift from the normal animal baseline towards the untreated DH phenotype.

Examining Associations Between Legal Frameworks for Medical Planning and Intensity of End-of-Life Care

This study aims to understand the correlation between the legal framework around planning for medical treatment and the intensity of care received at the end of life. Advance directives (AD) allow an individual to legally document their wishes for medical treatment and end-of-life care, and durable powers of attorney (DPOA) allow them to identify an individual to make medical decisions on their behalf in the event they are no longer able. These laws vary greatly across time, place, and in their complexity. We estimated fixed effects model, which controls for time-invariant and state-specific factors affecting end-of-life care. Our primary outcome variable is the number of inpatient hospital days during the last six months of life, sourced from the Dartmouth Atlas Project. Our explanatory variables are hand-collected state-level legal statutes including whether the state (a) has default surrogate laws, (b) recognizes the ability to create a DPOA and/or AD, (c) permits oral directives, (d) authorizes a combined AD/DPOA, and (e) provides an official registry for ADs. Preliminary findings show recognizing DPOA and AD are negatively correlated with our outcome variable (-2.6 days; Std err 0.272) as are having default surrogate laws (-0.36 days; std err 0.157). However, allowing oral directives had an opposite effect (-.46 days; std err 0.157). Neither authorized combined AD/DPOAs nor AD registries resulted with significant correlations. These findings indicate that the existence of a basic framework such as default surrogate laws and a law governing ADs are key policy features correlated with reduced intensity in end-of-life care.

Abstract PO-111: Postoperative lung cancer pain over 4 days: Changes in painful body surface area

Abstract Introduction: It is unknown if the body surface area measure is sensitive to the change in pain over the first four days after lung cancer surgery. Known for cancer health disparities, improving pain outcomes for patients with lung cancer could have implications for reducing disparities. The purpose of this study was to compare body surface area over the first four days post thoracotomy for lung cancer. Methodology: In a repeated measures observational study, 41 lung cancer patients (mean age 60±12 years, 80% male, 100% Turkish) who had thoracotomy surgery reported pain postoperatively for four days. Patients were asked to mark on a body outline the location of the area where they had pain each day using PAINReportIt, a valid and reliable electronic version of the McGill Pain Questionnaire, on an Internet-enabled Surface Pro tablet. The number of sites that the patient marked was counted automatically by PAINReportIt. Then the body surface area percentage (BSA%) was calculated using ImageJ software. Each day patients were asked to rate on a 0-10 scale the pain intensity they were currently having and the least and worst that the pain was in the past 24 hours. These 3 values were used to create the average of pain intensity (API) the patient experienced for each of the four days. Analyses included scatter plots, descriptive statistics, longitudinal analysis of BSA% using linear mixed effects model, and Pearson correlations of BSA% and API. Results: The mean number of pain sites recorded by PAINReportIt for each postop day 1 to 4 was 2.1±0.7, 2.2±0.7, 2.1±0.9, and 1.9±0.7, respectively (p=.152). The mean BSA% on postop days 1 to 4 was 2.1%±1.9%, 2.4%±2.2%, 2.5%±2.7%, and 2.2%±2.4%, respectively. The correlations between postop day 1-4 values were high (r=.68 to r=.86). Longitudinal analysis shows that the time trend was not statistically significant: b=0.023, Std Err=0.094, 5=0.242, p=.81. The API significantly decreased over the 4 postop days: 7.3±1.8, 5.6±1.8, 4.2±1.9, and 3±2.1, respectively (p=.000). The correlations between BSA% and API on each of the 4 postop days were: r=-.56, p<.001, r=-.15, p=.36, r=-.03, p=.85, and r=-.05, p=.78. The negative relationship between BSA% and API was unexpected and scatter plots show that at very high pain and very low pain, BSA%s were low. High BSA% values were mostly observed at moderate pain. This inverse U shape relationship explains the correlations between BSA% and API at different time points. Conclusions: In a sample of patients who had thoracotomy for lung cancer, the BSA% was not sensitive to recovery over the first 4 days after surgery, but the API was. This finding is likely due to the few pain sites and small areas marked on the body outline to represent the pain of the surgical incision and chest tubes. In the post thoracotomy lung cancer population, BSA% is not likely to be a measure that will help reduce cancer health disparities. Citation Format: Mecca M. James, Sevgi D. Dogan, Seda K. Yedir, Rishabh Garg, Yingwei Yao, Sevily Erden, Diana J. Wilkie. Postoperative lung cancer pain over 4 days: Changes in painful body surface area [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-111.

Comparison of Forecasting the Number of Outpatients Visitors Based on Naïve Method and Exponential Smoothing

This paper aimed to predict outpatient visits from both general and BPJS category based on the Naïve and the Exponential Smoothing method, these two methods are compared to obtain the best method in predicting outpatient visits at XYZ hospitals. The data that were processed in this paper is based solely on the annual data collection over a period of 5 years from 2014-2018 which consists of 2 categories, namely general visit data and BPJS visit data. The annual general category data has the following data amounts: 2014 = 11028, 2015 = 12950, 2016 = 17587, 2017 = 21951, and 2018 = 19049. As for the BPJS visit data, the data as follows 2014 = 16869, 2015 = 14059, 2016 = 14217, 2017 = 13019, and 2018 = 9641. Results of predictions number of outpatient visits from Naïve method on the visit data which is categorized as general has MSE 5191788 and MAPE values of 16.335%, the categorized BPJS has a value of MSE 13165490 and MAPE 19.081%. While the Exponential Smoothing method on the visit data that is categorized as general has MSE 7790587 and MAPE values of 21.808%, BPJS category only having MSE 13165490 and MAPE values of 20.718%. Of the two methods, the method considered better is the Naïve method which has a percentage of MAPE values <20%. It can be concluded that the Naïve method is more suitable for forecasting the number of visits from the general category and BPJS compared to the Exponential Smoothing method because the forecast value and the std err are smaller.

Grazing exclusion—An effective approach for naturally restoring degraded grasslands in Northern China

AbstractNearly 90% of the 390 million ha of grasslands in northern China are degraded. ‘Grazing exclusion’ has been implemented as a nature‐based solution to rejuvenate degraded grasslands, but the effectiveness of the rejuvenation processes is uncertain. Here, we investigated the effects of grazing exclusion on aboveground plant community traits, soil physiochemical and biological properties, and the mechanisms responsible for enhanced grassland rejuvenation. A meta‐analysis across various studies was used to assess the effectiveness. On average, grazing exclusion improved vegetation coverage by 18.5 percentage points and increased aboveground biomass by 1.13 t ha−1 and root biomass by 1.27 t ha−1, which represent an increase of 84%, 246%, and 31%, respectively, compared with continuous grazing practices. Grazing exclusion reduced soil bulk density by 13.7% and increased soil water content by 68.9%. Grasslands under grazing exclusion increased soil organic carbon (SOC) in the 0‐ to 15‐cm depth by 3.95 (±0.35 Std err) t ha−1 and total soil N, available N, and total soil P in the 0‐ to 40‐cm depth by 2.39 (±0.14), 0.83 (±0.37), and 1.96 (±0.44) t ha−1, respectively, compared with continuous grazing; these values represent an increase of 31%, 25%, 23%, and 14%, respectively. Prolonging the duration (years) of grazing practices enlarged the differences in SOC and soil N content between grazing exclusion and continuous grazing. Grazing exclusion has improved plant community traits and enhanced soil physiochemical and biological properties of degraded grasslands, and thus, this ‘nature‐based’ approach can serve as an effective means to rejuvenate degraded grasslands.

Low Sperm Counts: Biophysical Profiles of Oligospermic Males in Sub-Saharan Africa

Introduction: Male infertility is a public health burden and a psychological dilemma in the life of the affected man. Subjects and Methods: A total of 911 men were studied retrospectively, from 2010 to 2015. Among these, 49.7% had normal sperm count, 39.3% were oligospermic and 12.0% were azoosper-mic. Azoospermic men were withdrawn from this study solely to investigate the seminal fluid parameters and the biophysical characteristics of oligospermic men in contrast to those with normal sperm count. Age was stratified into <30, 30 - 39.9, 40 - 49.9, 50 - 59.9 and ≥60 years; body mass index was categorized into underweight (<18.5), normal (18.5 - 24.9), overweight (25.0 - 29.9) and obese (≥30) and standard semen analysis was performed. Results: The means (±sd) of age and of BMI of the 802 subjects of the study were 42.7 (±7.0) years and 26.9 (3.9) kg/m2 respectively. There was no significant difference in the age or BMI of normal and oligospermic men. A total of 453 (56.5%) had normal sperm count while 349 (43.5%) were oligospermic. Compared to normal weight men, those overweight and those obese were, respectively, 1.11 (χ2 = 0.44, P-value = 0.51, OR = 1.11, 95% CI = 0.81, 1.54) and 1.56 times (χ2 = 4.50, P-value = 0.03, OR = 1.56, 95% CI = 1.03, 2.36) more likely to be oligo-spermic. The mean of normal oval head sperms was significantly higher (t = -7.31, P-value = 0.00001) in normal men (47.8 ± 8.9) than in oligospermic men (43.0 ± 10.7). Oligospermic men were over 4 times as likely to produce progressive sperm motility of <32% (χ2 = 70.90, P-value = 0.000001, OR = 4.24, 95% CI = 2.99, 6.02) than men with normal sperm count. Multivariate regression analysis shows negative but significant correlations between age and semen volume (coef. = - 0.04, Std Err. = 0.01, t = - 4.01, P-value = 0.0001, 95% CI: - 0.06, - 0.02) and between BMI and sperm count (coef. = - 0.18, Std Err. = 0.06, t = - 3.26, P-value = 0.001, 95% CI: - 0.29, - 0.07). Conclusion: Our findings suggest that overweight and obesity are associated with oligospermia and oligospermia is significantly linked with low progressive motility, and various sperm cell defects.

Men without Sperms

Introduction: Men without sperm (azoospermic) make up about 15% of all infertile men in reproductive age of fatherhood. Male infertility is a health and social problem in many communities. Subjects and Methods: This retrospective study was carried from 2010 to 2015. Initially, 907 men were included in the study among whom 109 (12.02%), 346 (38.15%) and 452 (49.83%) were azoospermic, oligospermic and normospermic, respectively. This study only investigated the association between age, BMI, semen volume, liquefaction time and pus cells among normospermic and azoospermic men. Standard semen analysis was performed and subjects were categorized by age into Results: The 562 subjects of the study had means (±sd) age of 42.6 (±7.10) years and BMI of 27.0 (4.1) kg/m2 respectively. In all, 109 (19.4%) were azoospermic. Overweight and obese men were, respectively, more than 1½ and about 2½ times more likely to be azoospermic compared to normal weight men. Azoospermic men were significantly heavier than men with normal sperm count (t = -0.34; P-value = 0.003). Among those with normal weight, liquefaction time was significantly shorter (t = 5.49, P-value = 0.000001) in azoospermic (28.70 min.) than in men with normal sperm count (31.82 min.). Obese azoospermic men were about 4 times as likely to have high pus cells in semen than normal weight azoospermic men (OR = 3.82; 95% CI: 0.39, 37.01). Multivariate regression analysis shows a strong but negative coefficient correlation between sperm concentration and BMI (coef. = -0.48, Std Err. = 0.25, P-value = 0.05, 95% CI: -0.96, 0.10). Conclusion: Our findings suggest that high BMI is associated with azoospermia. Azoospermia also did not seem to negatively impact liquefaction time.

Long-Term Outcomes for Validation of Cardiac-Sparing Breast Cancer Treatment Techniques

The association between radiation therapy (RT) and ischemic vascular disease (IVD) has been known for many decades. The publication in 2013 of a retrospective study linking RT for left breast cancer to IVD has inspired numerous dosimetric studies aimed at reducing cardiac doses. The cardiac risk has been attributed to attempts to treat internal mammary lymph nodes (IMLN), most commonly using an anterior beam that delivered high doses to the origins of major vessels and much of the myocardium. If a treatment technique is producing clinically significant IVD we should see a detrimental effect on survival for patients with left breast cancers compared to those with right breast cancers. In 1983 our facility began using CT images to guide treatment planning. Initially, conformal molded blocks shaped tangent fields to protect the cardiac profile as much as possible. Anterior or oblique internal mammary fields became very rare. Since 2001 we have used 3D conformal CT planning and multi-leaf collimators to the same purpose. Deep inspiration breath hold is used when indicated. Between 1983 and 2011 a total of 3474 patients (1735 R, 1739 L) with first primary pathologic stages 0-III breast cancers were treated with this philosophy. Treatment generally covered the whole breast with standard doses (typically 45 – 50 Gy) and a boost. Since 1982 patient data has been abstracted by certified cancer registrars from general medical records and RT summary letters, and maintained on an in-house registry system. The registry has current follow-up on 95.6% of all cases in this group and was the source of data for this study. The two groups proved to be very closely matched in patient and tumor characteristics. Survival estimates were calculated for 30 years following diagnosis using the Kaplan-Meier method on 1 day intervals (table). These were compared using the log-rank test. Throughout the 30-year period of analysis the P-value was never smaller than 0.23 (briefly, at 7 years). Clinically significant IMLN recurrence has been very rare. Cause-specific mortality declined substantially after about 15 years but all-cause mortality remained elevated. For any RT technique, the average heart dose is substantially smaller for right breast cancers than it would be for left breast cancers. The equivalent survival seen with these two groups suggests that relatively simple alterations to treatment plans can virtually eliminate excess cardiac mortality from left breast irradiation without adverse consequences.Tabled 1Abstract 2130; Table 1LateralityTime from Dx (Yrs)051015202530RightAt Risk173514988944691935811Survival100.00%87.35%73.30%59.03%46.65%35.84%22.15%Std Err of Survival0.00%0.81%1.28%1.79%2.52%3.80%6.18%LeftAt Risk173914929124691816614Survival100.00%87.29%71.97%59.14%45.73%34.19%28.80%Std Err of Survival0.00%0.81%1.28%1.77%2.58%3.52%6.49% Open table in a new tab

Malaria Related Perceptions, Care Seeking after Onset of Fever and Anti-Malarial Drug Use in Malaria Endemic Settings of Southwest Ethiopia.

BackgroundPrompt care seeking and appropriate use of anti-malarial drugs are critical components of malaria prevention and control. This study assessed malaria related perceptions, care seeking behavior and anti-malarial drug use in malaria endemic settings of Ethiopia.MethodsData were generated from a community based cross-sectional study conducted among 798 households during January 2014 as part of a larger household behavioral study in three malaria endemic districts of Jimma Zone, Southwest Ethiopia. Both quantitative and qualitative data were collected and analyzed using SPSS 17.0 and STATA 12.0.ResultsIn this study, only 76.1% of the respondents associated malaria to mosquito bite, and incorrect beliefs and perceptions were noted. Despite moderate level of knowledge (estimated mean = 62.2, Std Err = 0.7, 95% CI: 60.6–63.8%), quite high favorable attitude (overall estimated mean = 91.5, Std Err = 0.6, 95% CI: 90.1–92.9%) were recorded towards malaria preventive measures. The mean attitude score for prompt care seeking, appropriate use of anti-malarial drugs, LLIN use and Indoor Residual Spray acceptance was 98.5 (Std Err = 0.4, 95% CI:97.5–99.4), 92.7 (Std Err = 0.6 95% CI:91.5–93.9), 88.8 (Std Err = 0.5, 95% CI:85.5–92.1) and 86.5 (Std Err = 1.2, 95% CI: 83.9–89.1), respectively. The prevalence of fever was 2.9% (116/4107) and of the study participants with fever, 71.9% (95% CI: 65.5–78.3%) sought care and all of them consulted formal health care system. However, only 17 (19.8%) sought care within 24 hours after onset of fever. The frequency of care seeking was higher (77.8%, n = 21/27) and more prompt (28.6%, 6/21) for children under five as compared to old age groups despite it was not statistically significant (p > 0.05). However, higher median time of seeking first care was observed among Muslims and people who did not attend school (p < 0.05). Of those who used anti-malarial drugs, 9.1% indicated that they used it inappropriately through saving and/or sharing. Irregular availability of anti-malarial drugs; irregular presence of frontline health workers and misconceptions were mentioned to contribute to delayed care seeking and irrational use of anti-malarial drugs.ConclusionsAlthough care seeking behavior for febrile illness was quite high in this community, the habit of prompt care seeking was very limited. Thus, malaria prevention and control programs need to take into account local misconceptions and wrong perceptions, and health system factors to achieve optimal health seeking behavior in such malaria endemic settings.

Chronotype and Improved Sleep Efficiency Independently Predict Depressive Symptom Reduction after Group Cognitive Behavioral Therapy for Insomnia.

Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve both sleep and depressive symptoms, but predictors of depression outcome following CBT-I have not been well examined. This study investigated how chronotype (i.e., morningness-eveningness trait) and changes in sleep efficiency (SE) were related to changes in depressive symptoms among recipients of CBT-I. Included were 419 adult insomnia outpatients from a sleep disorders clinic (43.20% males, age mean ± standard deviation = 48.14 ± 14.02). All participants completed the Composite Scale of Morningness and attended at least 4 sessions of a 6-session group CBT-I. SE was extracted from sleep diary; depressive symptoms were assessed using the Beck Depression Inventory (BDI) prior to (Baseline), and at the end (End) of intervention. Multilevel structural equation modeling revealed that from Baseline to End, SE increased and BDI decreased significantly. Controlling for age, sex, BDI, and SE at Baseline, stronger evening chronotype and less improvement in SE significantly and uniquely predicted less reduction in BDI from Baseline to End. Chronotype did not predict improvement in SE. In an insomnia outpatient sample, SE and depressive symptoms improved significantly after a CBT-I group intervention. All chronotypes benefited from sleep improvement, but those with greater eveningness and/or less sleep improvement experienced less reduction in depressive symptom severity. This suggests that evening preference and insomnia symptoms may have distinct relationships with mood, raising the possibility that the effect of CBT-I on depressive symptoms could be enhanced by assessing and addressing circadian factors.

Cytotoxicity of HBD3 for dendritic cells, normal human epidermal keratinocytes, hTERT keratinocytes, and primary oral gingival epithelial keratinocytes in cell culture conditions.

Human β-defensin 3 (HBD3) is a prominent host defense peptide. In our recent work, we observed that HBD3 modulates pro-inflammatory agonist-induced chemokine and cytokine responses in human myeloid dendritic cells (DCs), often at 20.0 μM concentrations. Since HBD3 can be cytotoxic in some circumstances, it is necessary to assess its cytotoxicity for DCs, normal human epidermal keratinocytes (NHEKs), human telomerase reverse transcriptase (hTERT) keratinocytes, and primary oral gingival epithelial (GE) keratinocytes in different cell culture conditions. Cells, in serum free media with resazurin and in complete media with 10% fetal bovine serum and resazurin, were incubated with 5, 10, 20, and 40 μM HBD3. Cytotoxicity was determined by measuring metabolic conversion of resazurin to resorufin. The lethal dose 50 (LD50, mean μM±Std Err) values were determined from the median fluorescent intensities of test concentrations compared to live and killed cell controls. The LD50 value range of HBD3 was 18.2-35.9 μM in serum-free media for DCs, NHEKs, hTERT keratinocytes, and GE keratinocytes, and >40.0 μM in complete media. Thus, HBD3 was cytotoxic at higher concentrations, which must be considered in future studies of HBD3-modulated chemokine and cytokine responses in vitro.

Measurement of gastric meal and secretion volumes using magnetic resonance imaging

MRI can assess multiple gastric functions without ionizing radiation. However, time consuming image acquisition and analysis of gastric volume data, plus confounding of gastric emptying measurements by gastric secretions mixed with the test meal have limited its use to research centres. This study presents an MRI acquisition protocol and analysis algorithm suitable for the clinical measurement of gastric volume and secretion volume. Reproducibility of gastric volume measurements was assessed using data from 10 healthy volunteers following a liquid test meal with rapid MRI acquisition within one breath-hold and semi-automated analysis. Dilution of the ingested meal with gastric secretion was estimated using a respiratory-triggered T1 mapping protocol. Accuracy of the secretion volume measurements was assessed using data from 24 healthy volunteers following a mixed (liquid/solid) test meal with MRI meal volumes compared to data acquired using gamma scintigraphy (GS) on the same subjects studied on a separate study day. The mean ± SD coefficient of variance between 3 observers for both total gastric contents (including meal, secretions and air) and just the gastric contents (meal and secretion only) was 3 ± 2% at large gastric volumes (>200 ml). Mean ± SD secretion volumes post meal ingestion were 64 ± 51 ml and 110 ± 40 ml at 15 and 75 min, respectively. Comparison with GS meal volumes, showed that MRI meal only volume (after correction for secretion volume) were similar to GS, with a linear regression gradient ± std err of 1.06 ± 0.10 and intercept −11 ± 24 ml. In conclusion, (i) rapid volume acquisition and respiratory triggered T1 mapping removed the requirement to image during prolonged breath-holds (ii) semi-automatic analysis greatly reduced the time required to derive measurements and (iii) correction for secretion volumes provided accurate assessment of gastric meal volumes and emptying. Together these features provide the scientific basis of a protocol which would be suitable in clinical practice.

Movement Artefact Resistant Photoplethysmographic Probe

Photoplethysmogram (PPG) is an exceptionally informative diagnostic tool, but the signal registered by wearable devices usually is corrupted, because the probe is affected by the external force and moves with respect to the point of the measurement during the physical activities of the human. This problem is solved usually applying some techniques for the PPG extraction from the corrupted (noisy) signal. The authors of this paper are suggesting the solutions, which prevent corruption of PPG instead of noise filtering or other PPG extraction from corrupted signal techniques. One of such solutions is described in this paper, by proposing special photoplethysmographic signal probe (PPGP). This device emits the amplitude modulated light beam with special code sequence, which like Barker code, can be easily recognized using correlation method. The experimental evaluation of proposed method showed, that even in case of a very high noise level SNR=0dB correlation between reference PPG and photoplethysmogram got using proposed method is remarkable, reaching corr = 0.985, while standard deviation of error is small and equal std(err)=0.33. DOI: http://dx.doi.org/10.5755/j01.eee.20.3.6681

EPA-0586 – Comparison of sensitivity to facial emotions between patients with anorexia nervosa and matched controls using a morphing test (multimorph): a prospective study

In patients with Anorexia Nervosa (AN), troubles in facial emotion recognition (FER) have been reported using methodologies relying mainly on static tests. The morphing technique allows new perspectives in experimentation, by using dynamic expressions of emotions. To compare prospectively FER using Multimorph, a morphing technique previously described (Robin, 2012) in anorexic patients and matched controls. Population: 27 female patients with DSM-IV criteria for AN and 27 healthy individually matched controls were prospectively studied. Multimorph protocol: Participants had to identify as rapidly as possible the 6 basic emotions. Emotions were displayed progressively by 2.5% incremental stages from neutral (0%) to a full-blend (100%) facial emotion (40 stages were displayed by trial). Each subject completed 36 trials (6 face x 6 emotions). Results are expressed as mean number of stages until the first correct response. Data were analyzed with a 2 (AN versus control) × 6 (anger, disgust, fear, happiness, sadness and surprise) factorial design. Comparisons were made with ANOVA for repeated measurements using Generalized Estimating Equations approach (Lipsitz, 1994). A p value < 0.05 was considered as significant. AN Patients (n=27) Controls (n=27) Mean difference Std Err p value Anger 28.8 30.3 -1.4245 1.0016 0.1609 Disgust 29.2 28.9 0.3228 0.9818 0.7437 Sadness 29.0 30.0 -0.9854 0.9274 0.2929 Fear 31.8 31.2 0.6057 0.8024 0.4538 Surprise 25.9 27.5 -1.6409 0.9578 0.0926 Happiness 18.7 21.4 -2.7248 0.8690 0.0028 ALL 27.0 28.0 -1.0266 0.3768 0.0088 Anorexic patients have an increased sensitivity to facial emotions, compared to controls.

SU‐E‐T‐689: Effects of Coordinate System Orientation On ICRU Bladder Point Dose

Purpose: To quantify the displacement and dosimetric errors on position of the ICRU bladder point due to coordinate system orientation in gynecological HDR procedures. Methods: Eight patients (23 treatment fractions) receiving HDR brachytherapy for gynecological malignancies were evaluated. Bladder points were placed for each of two coordinate systems (ICRU and applicator) for each patient fraction. The ICRU coordinate system refers to true anatomical orientations (e.g., ant/post) while the applicator coordinate system is transformed (translated and rotated) based on the location and orientation treatment applicator and is used to define prescription points and optimize planned dose distributions. In both cases, the ICRU bladder point definition was used to place the point (most posterior point of foley balloon on lateral image and center of foley balloon on AP image) with differences resulting from definition of coordinate system orientation. The displacement in three dimensions and point dose differences were calculated for each patient fraction. Results: Point displacement of the applicator coordinate system point (Bappl) relative to the ICRU point (BICRU) was 6.3 ± 0.7 mm (mean ± std err) with a range of 1.5 to 12.6 mm, a statistically significant Result. Dosimetrically, dose to Bappl was 7.3 ± 1.6% (mean ± std err) of the prescribed dose higher than BICRU with a range of −7.9 to 24.7%, a statistically and clinically significant Result. This results in an overestimation of bladder dose when using the applicator coordinate system and using ICRU point dose criteria for plan evaluation. Conclusion: Failure to use a true anatomical coordinate system can lead to statistically and clinically significant dosimetric errors in dose to the defined bladder point. Use of the applicator coordinate system to define the bladder point can potentially cause compromises in plan quality in attempting to meet normal tissue dose tolerances evaluated with incorrectly reported doses.

Dosimetric intercomparison for multicenter clinical trials using a patient‐based anatomic pelvic phantom

To assess dose delivery accuracy to clinically significant points in a realistic patient geometry for two separate pelvic radiotherapy scenarios. An inhomogeneous pelvic phantom was transported to 36 radiotherapy centers in Australia and New Zealand. The phantom was treated according to Phase III rectal and prostate trial protocols. Point dose measurements were made with thermoluminescent dosimeters (TLDs) and an ionisation chamber. Comprehensive site-demographic, treatment planning, and physical data were collected for correlation with measurement outcomes. Dose delivery to the prescription point for the rectal treatment was consistent with planned dose (mean difference between planned and measured dose - 0.1 ± 0.3% std err). Dose delivery in the region of the sacral hollow was consistently higher than planned (+1.2 ± 0.2%). For the prostate treatment, dose delivery to the prostate volume was consistent with planned doses (-0.49 ± 0.2%) and planned dose uniformity, though with a tendency to underdose the PTV at the prostate-rectal border. Measured out-of-field doses were significantly higher than planned. A phantom based on realistic anatomy and heterogeneity can be used to comprehensively assess the influence of multiple aspects of the radiotherapy treatment process on dose delivery. The ability to verify dose delivery for two trials with a single phantom was advantageous.

Multi-carbonate component reconstruction of mid-carboniferous (Chesterian) seawater δ13C

This study presents the first stratigraphically continuous δ 13C carb record for the Chesterian interval developed from Antler foreland basin platform successions. The bulk carbonate-derived δ 13C curve was constructed using ∼ 700 biostratigraphically constrained samples providing a 10 5-yr resolution. A multi-component study of δ 13C and δ 18O variability in petrographically and geochemically screened abiotic and biogenic calcite components delineates the degree of preservation and δ 13C heterogeneity in these ancient epicontinental carbonates. Furthermore, it constrains the influence of kinetic and vital effects, and local-to-regional-scale C cycling on their δ 13C carb values. The δ 13C and δ 18O values of micrites and bulk carbonates overlap regardless of lithofacies and show minimal intrasample variability. Overall, biogenic calcite δ 13C and δ 18O values are higher than the average isotope compositions of bulk carbonates and micrites, although δ 13C values in contemporaneous samples are only minimally (0.3‰; 2 std err of ± 0.3‰) different relative to much larger differences in δ 18O values. Although brachiopod δ 13C and δ 18O values are higher than average bulk carbonate and micrite values, their δ 13C values exhibit considerable isotopic variability by taxa and ultrastructure. Notably, the δ 13C values of brachiopod secondary shell layers overlap with bulk carbonate, micrite and marine cement δ 13C values. Conversely, δ 13C values of brachiopod tertiary prismatic layers, including Composita, are on average 2 to 5‰ higher than the δ 13C values of contemporaneous bulk carbonates, micrites and brachiopod secondary shell layers. An observed average ∼ 2‰ decrease in the δ 13C values of secondary cross-bladed laminar layers in productids relative to contemporaneous bulk carbonate, micrite and marine cement values suggests a previously unrecognized kinetic and/or vital effect on Carboniferous productid δ 13C values given that they have the highest δ 18O values of all analyzed components. The observed higher δ 13C values in these tertiary prismatic layers are comparable to greater than the 13C-enrichment (∼ 1‰) previously documented in Pennsylvanian Composita. The overlap in δ 13C values of bulk carbonates with diagenetically screened, microdrilled matrix, marine cements and brachiopod secondary shell layers indicates that the Chesterian bulk carbonate-derived δ 13C values may reliably record, to within 1‰, the evolution of ambient seawater δ 13C in the outer carbonate ramp of the Antler basin. Comparison of the Chesterian δ 13C record to the bulk-carbonate C isotope curve derived from the Arrow Canyon, NV carbonate succession, further suggests that these bulk carbonate-derived δ 13C records are reliable proxies of the composition and trends in seawater δ 13C regionally along the equatorial eastern Panthalassan margin. The newly resolved Chesterian stratigraphy documents multiple δ 13C excursions, including previously unrecognized significant C isotope shifts. A shift to higher frequency and amplitude shorter-term δ 13C fluctuations in the upper third of the Chesterian Stage occurred simultaneously with a change in stratigraphic cyclicity from dominantly 3rd-order to 4th-order carbonate cycles suggesting a mechanistic linkage between ambient seawater δ 13C and sea-level fluctuations in the Antler basin. This change in the character of the shorter-term δ 13C fluctuations coupled with a subsequent significant (∼ 4‰) positive C isotope excursion across the mid-Carboniferous boundary, previously recognized in all Carboniferous curves, is interpreted to record the onset of late Paleozoic glaciation and glacio-eustasy.