Assessment of delivered dose in prostate cancer patients treated with ultra-hypofractionated radiotherapy on 1.5-Tesla MR-Linac.

Objective: To quantitatively characterize the dosimetric effects of long on-couch time in prostate cancer patients treated with adaptive ultra-hypofractionated radiotherapy (UHF-RT) on 1.5-Tesla magnetic resonance (MR)-linac. Materials and methods: Seventeen patients consecutively treated with UHF-RT on a 1.5-T MR-linac were recruited. A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate. We collected data for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. Results: Overall, 290 MR scans were collected (85 pre-MR, 85 PV-MR, 49 Bn-MR and 71 post-MR scans). With a median on-couch time of 49 minutes, the mean planning target volume (PTV)-V95% of all scans was 97.83 ± 0.13%. The corresponding mean clinical target volume (CTV)-V100% was 99.93 ± 0.30%, 99.32 ± 1.20%, 98.59 ± 1.84%, and 98.69 ± 1.85%. With excellent prostate-V100% dose coverage, the main reason for lower CTV-V100% was slight underdosing of seminal vesicles (SVs). The median V29 Gy change in the rectal wall was -1% (-20%-17%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. Conclusions: This 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period with adaptive ATS workflow on 1.5-T MR-linac, albeit with a relatively long on-couch time. The 3-mm CTV-PTV margin was adequate for prostate irradiation but occasionally insufficient for SVs. More attention should be paid to restricting high-dose RT to the rectal wall when optimizing the ATS plan.

Patient Assessment and Therapy Planning Based on Homologous Recombination Repair Deficiency.

Defects in genes involved in the DNA damage response cause homologous recombination repair deficiency (HRD). HRD is found in a subgroup of cancer patients for several tumor types, and it has a clinical relevance to cancer prevention and therapies. Accumulating evidence has identified HRD as a biomarker for assessing the therapeutic response of tumor cells to poly(ADP-ribose) polymerase inhibitors and platinum-based chemotherapies. Nevertheless, the biology of HRD is complex, and its applications and the benefits of different HRD biomarker assays are controversial. This is primarily due to inconsistencies in HRD assessments and definitions (gene-level tests, genomic scars, mutational signatures, or a combination of these methods) and difficulties in assessing the contribution of each genomic event. Therefore, we aim to review the biological rationale and clinical evidence of HRD as a biomarker. This review provides a blueprint for the standardization and harmonization of HRD assessments.

Radiomics assessment of carotid intraplaque hemorrhage: detecting the vulnerable patients.

BACKGROUND: Intraplaque hemorrhage (IPH), one of the key features of vulnerable plaques, has been shown to be associated with increased risk of stroke. The aim is to develop and validate a CT-based radiomics nomogram incorporating clinical factors and radiomics signature for the detection of IPH in carotid arteries. METHODS: This retrospective study analyzed the patients with carotid plaques on CTA from January 2013 to January 2021 at two different institutions. Radiomics features were extracted from CTA images. Demographics and CT characteristics were evaluated to build a clinical factor model. A radiomics signature was constructed by the least absolute shrinkage and selection operator method. A radiomics nomogram combining the radiomics signature and independent clinical factors was constructed. The area under curves of three models were calculated by receiver operating characteristic analysis. RESULTS: A total of 46 patients (mean age, 60.7 years ± 10.4 [standard deviation]; 36 men) with 106 carotid plaques were in the training set, and 18 patients (mean age, 61.4 years ± 10.1; 13 men) with 38 carotid plaques were in the external test sets. Stenosis was the independent clinical factor. Eight features were used to build the radiomics signature. The area under the curve (AUC) of the radiomics nomogram was significantly higher than that of the clinical factor model in both the training (p = 0.032) and external test (p = 0.039) sets. CONCLUSIONS: A CT-based radiomics nomogram showed satisfactory performance in distinguishing carotid plaques with and without intraplaque hemorrhage.

Overall structural seismic damage rapid assessment method based on period and displacement response characteristics.

The seismic damage state of building structure can be rapidly evaluated by coupling effect of structural displacement response and periodic characteristics. Firstly, the fundamental period calculation formula that adapts to the deformation pattern and distribution mode of horizontal seismic action for reinforced concrete frame structure is derived. Secondly, the seismic damage assessment standard of building structure considering period variation is established. Then, the seismic damage assessment method of building structure is constructed. Finally, the seismic damage example is used to verify the established evaluation method. The results show that the established research method has high accuracy and good engineering practicability.

Differential responses of bloom-forming Ulva intestinalis and economically important Gracilariopsis lemaneiformis to marine heatwaves under changing nitrate conditions.

Marine heatwaves (MHWs) are affecting the survival of macroalgae. However, little is known regarding how the impacts of MHWs are regulated by nitrogen availability. In this study, we investigated the physiological and genetic responses of a green-tide macroalga Ulva intestinalis Linnaeus and a commercially cultivated macroalga Gracilariopsis lemaneiformis (Bory) E.Y. Dawson, Acleto & Foldvik under different nitrate conditions to simulated MHWs. Under nitrogen limited conditions (LN), heatwaves did not significantly affect biomass or Fv/Fm of U. intestinalis although it led to an earlier biomass decline due to more reproduction events, and meanwhile an upregulation in genes related to TCA cycle and oxidative phosphorylation was detected, supporting sporulation. Under nitrogen replete conditions (HN), heatwaves did not change biomass, Fv/Fm or photosynthetic pigments but reduced reproduction rate along with insignificant change of oxidative phosphorylation and TCA cycle related genes. Meanwhile, genes related to photosynthesis and glutathione metabolism were upregulated. Regarding G. lemaneiformis, heatwaves reduced its Fv/Fm and photosynthetic pigments content, leading to bleaching and death, and photosynthesis-related genes were also downregulated at LN. Fv/Fm was improved and photosynthesis-related genes were up-regulated by the combination of nitrogen enrichment and heatwaves, whereas G. lemaneiformis remained bleached and died by day 12. Therefore, U. intestinalis could survive heatwaves through shifting to micropropagules at LN and protecting its photosynthesis at HN. In contrast, G. lemaneiformis died of bleaching when suffering heatwaves regardless of nitrogen availability. These findings suggest that in future oceans with eutrophication and MHWs, the harmful alga U. intestinalis may have more advantages over the economic alga G. lemaneiformis.

Evaluation of groundwater sustainable development considering seawater intrusion in Beihai City, China.

The overmining of groundwater makes the aquifer in a coastal area prone to seawater intrusion and further leads to deterioration of water quality and ecosystem degradation. However, the vulnerability evaluation of seawater intrusion can provide a scientific basis for the prevention of seawater intrusion, and then ensure the sustainable use of groundwater. In this paper, Baihai City was taken as the study area, and the analytic hierarchy process (AHP), variable power theory, and fuzzy comprehensive evaluation method were used synthetically. The vulnerability of seawater intrusion in the study area was divided into lowest vulnerability, low vulnerability, medium vulnerability, and high vulnerability, and these correspond to 1739.98, 133.88, 664.32, and 737.55 km2. On this basis, combined with the groundwater quality and quantity and ecosystem of the study area, the groundwater is divided into concentrated groundwater supply area (8.16%), decentralized groundwater supply area (12.44%), protected area (78.94%), and reserved zone (0.45%), which can provide the basis for the rational exploitation and management of groundwater. By analyzing the results of constant right and variable weight evaluation, combined with the history of seawater intrusion, it is proved that the variable weight evaluation model can effectively solve the unreasonable situation caused by the internal differences of the indicator, so that the evaluation results are more in line with reality. In addition, the application of the fuzzy comprehensive evaluation method makes the evaluation results clearer.

Sustainable use zoning of land resources considering ecological and geological problems in Pearl River Delta Economic Zone, China.

The Pearl River Delta Economic Zone is one of the fastest growing areas of China's social and economic development. However, the contradiction between people and land, the deterioration of ecological environment and the damage of urban ecological security have become more serious problems. In previous studies there was single land utilization type in small-area and the evaluation method was not suitable to large areas, this study proposes a new method. Firstly, the study implements ecological land zoning from assessing the importance of ecosystem services functional in four aspects: biodiversity, water conservation, soil conservation and coastal protected zone. Then, the suitability evaluation index system of agricultural and construction land is established from the geological environment perspective, and introduces variable weight-analytical hierarchy process-comprehensive index model to evaluate the suitability of agricultural land and construction land. Re-zoning the type of land that has a special effect on the socio-economic, the mining land, protected area of geological relics and groundwater resources, respectively. Finally, considering the actual condition use status and suitability distribution of land, the results of comprehensive zoning of land utilization is got. The results of this study can provide some geological basis for the future land utilization zoning.

Quantitative assessment of cerebral connectivity deficiency and cognitive impairment in children with prenatal alcohol exposure.

It is common knowledge that alcohol consumption during pregnancy would cause cognitive impairment in children. However, recent works suggested that the risk of drinking during pregnancy may have been exaggerated. It is critical to determine whether and up to which amount the consumption of alcohol will affect the cognitive development of children. We evaluate time-varying functional connectivity using magnetoencephalogram data from somatosensory evoked response experiments for 19 teenage subjects with prenatal alcohol exposure and 21 healthy control teenage subjects using a new time-varying connectivity approach, combining renormalised partial directed coherence with state space modeling. Children exposed to alcohol prenatally are at risk of developing a Fetal Alcohol Spectrum Disorder (FASD) characterized by cerebral connectivity deficiency and impaired cognitive abilities. Through a comparison study of teenage subjects exposed to alcohol prenatally with healthy control subjects, we establish that the inter-hemispheric connectivity is deficient for the former, which may lead to disruption in the cortical inter-hemispheric connectivity and deficits in higher order cognitive functions as measured by an IQ test, for example. We provide quantitative evidence that the disruption is correlated with cognitive deficits. These findings could lead to a novel, highly sensitive biomarker for FASD and support a recommendation of no safe amount of alcohol consumption during pregnancy.

[Hidden Markov models for human interactive behavior].

In order to meet the requirements in the cooperation and competition experiments for an individual patient in clinical application, two human interactive behavior key-press models based on hidden Markov model (HMM) were proposed. To validate the cooperative and competitive models, a verification experimental task was designed and the data were collected. The correlation of the score and subjects' participation level has been used to analyze the reasonability verification. Behavior verification was conducted by comparing the statistical difference in response time for subjects between human-human and human-computer experiment. In order to verify the physiological validity of the models, we have utilized the coherence analysis to analyze the deep information of prefrontal brain area. Reasonability verification shows that the correlation coefficient for the training data and the testing data is 0.883 1 and 0.578 6 respectively based on cooperation model, and 0.813 1 and 0.617 8 respectively based on the competition model. The behavioral verification result shows that the cooperation and competition models have an accuracy of 71.43% respectively. The results of physiological validity show that the deep information of prefrontal brain area could been extracted based on the cooperation and competition models, and reveal the consistency of coherence between the double key-press cooperative and competitive experiments, respectively. Above all, the high consistency is obtained between the cooperatio/competition model and the double key-press experiment by the behavioral and physiological evaluation results. Consequently, the cooperation and competition models could be applied to clinical trials.

Cost-effectiveness of microsurgical reconstruction for head and neck defects after oncologic resection.

BACKGROUND: Microvascular free tissue transfer has become the main technique used for head and neck reconstruction. We assessed the cost-effectiveness of free flap reconstruction for head and neck defects after oncologic resection for squamous cell carcinoma (SCC). METHODS: We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of reconstruction with free tissue transfer compared with locoregional flaps. Health state probabilities and quality of life scores were determined from literature. Costs were determined from institutional experience. Outcomes included quality-adjusted life years, costs, and incremental cost-effectiveness ratio. RESULTS: Free flap reconstruction was more costly than pedicled flap but associated with greater quality of life with no survival benefit. A value <$50,000 per quality-adjusted life-year (QALY) was defined as cost-effective. The incremental cost-effectiveness for head and neck free flap reconstruction was below the threshold and, therefore, free flap reconstruction is cost-effective. Reconstruction was more cost-effective for patients with lower stage cancers: $4643 per QALY for stage I SCC, $8226 for stage II, $17,269 for stage III, and $23,324 for stage IV. Univariate sensitivity analysis showed the cost-effectiveness would remain <$50,000 for all stages of SCC for all variables except for QALY after locoregional reconstruction without complications. CONCLUSION: Microsurgical head and neck reconstruction is cost-effective compared with locoregional flaps, even more so in patients with early-stage cancer. This finding supports the current practice of free flap head and neck reconstruction. Screening and early detection are important to optimize costs. © 2016 Wiley Periodicals, Inc. Head Neck 39: 541-547, 2017.

Care services for elderly people with dementia in rural China: a case study.

OBJECTIVE: To determine the state of the health and supportive services available to elderly people with dementia - and their families - in rural Lanxi county, in the province of Zhejiang, China. METHODS: In November 2014 and January 2015, we interviewed 14 key informants on dementia care face-to-face, using a semi-structured questionnaire. The informants included three rural physicians, an urban geriatrician, seven directors of institutions for the care of the elderly and three officials of the civil affairs bureau. We also completed in-depth interviews with five family caregivers of elderly people with dementia. FINDINGS: The interviewees indicated that there was a lack of specialized services designed specifically to address the needs of individuals with dementia and their family members. Non-psychiatric medical services and the available facilities for long-term care appeared to be ill-equipped to manage these needs. They lacked both clinical staff and standardized, evidence-based practices for the diagnosis, care, treatment and rehabilitation of patients with dementia. As care facilities often refused to admit elderly people with dementia, families were generally forced to care for elderly relatives with dementia at home. CONCLUSION: In Lanxi county - and probably in much of rural China - more public resources are needed to support family caregivers and to improve the capacity of care facilities for the elderly to care for individuals with dementia.

[Forecast the trend of burden from fatal road traffic injuries between 2015 and 2030 in China].

OBJECTIVE: To predict the burden caused by fatal road traffic injuries from 2015 to 2030. METHODS: We searched the websites of United Nations Population Division,United States Department of Agriculture, World Health Organization, China Energy Research Foundation and other agencies to obtain the predictive values of gross domestic product (GDP) per capita, urbanization, motorization and education from 2015 to 2030 in China. Predicted values were then applied to log-linear models to estimate the numbers and years of life lost due to road traffic injuries from 2015 to 2030. RESULTS: The mortality rate caused by road traffic injury decreased slightly, from 13.7/100 000 in 2015 to 11.8/100 000 in 2030. 191, 189, 183, 169 thousand persons were estimated to die from road traffic crashes in 2015, 2020, 2025 and 2030, respectively, showing a declining trend. Years of Life Lost (YLLs) caused by road traffic deaths were predicted to be 6 918, 6 634, 6 189, 5 513 thousand years in 2015, 2020, 2025 and 2030, respectively, also showing a gradual downward trend. But the YLLs displayed an increase among people at 55 years of age or older, between 2015 and 2030. Results from the sensitivity analysis showed a stable forecasting result. CONCLUSION: Mortality, number of deaths and YLLs from road traffic crashes were predicted to decrease slightly, between 2015 and 2030 but the number of deaths and YLLs due to road traffic injuries will continue to increase from 2015 to 2030.

Cost and outcome analysis of breast reconstruction paradigm shift.

Increased bilateral mastectomy for breast cancer treatment has generated an increased demand for bilateral breast reconstruction. This study examines changing patterns of reconstruction over the last decade to accommodate increased case volume and decreased morbidity associated with reconstruction. A single institution series of 3171 consecutive breast reconstruction cases of more than 10 years was divided into 2 periods, that is, 1999 to 2004 and 2005 to 2010. Bilateral breast reconstruction case volume increased 260% from 1999 to 2004 (n = 237) to 2005 to 2010 (n = 634). Mean patient age at diagnosis decreased by 7 years (P < 0.001). In 2005 to 2010, autologous reconstruction decreased from 60% to 26%, implant-based reconstruction increased from 40% to 74%. There was a noted increase in single-stage implant reconstruction and selective application of perforator flaps for bilateral autologous reconstruction (P < 0.001). Two-staged tissue expander reconstruction accounted for the greatest share of total cost (45%) in the later period. A younger patient demographic and increased case volume were accommodated through increased single-staged and prosthesis-based procedures.

Assessment of left atrial function by full volume real-time three-dimensional echocardiography and left atrial tracking in essential hypertension patients with different patterns of left ventricular geometric models.

OBJECTIVE: To evaluate left atrial function in essential hypertension patients with different patterns of left ventricular geometric models by real time three-dimensional echocardiography (RT-3DE) and left atrial tracking (LAT). METHODS: One hundred and thirty-three patients with essential hypertension were divided into four groups according to criteria proposed by Ganau et al: 36 patients in normal pattern group (I), 34 patients in concentric remodelling pattern group (II), 33 patients in concentric hypertrophy pattern group (III), and 30 patients in eccentric hypertrophy pattern group (IV). Thirty-two healthy volunteers were enrolled in this study. RT-3DE and LAT were used to obtain the volume-time and emptying fraction curves, and then the maximal volume, minimal volume, stroke volume, presystolic volume, ejection fraction, systolic filling rate, early diastolic emptying rate and late diastolic emptying rate of the left atrium were measured. Conduit volume and passive emptying volume of the left atrium were calculated. RESULTS: Left atrial indexes, conduit volume, passive emptying volume, and early diastolic emptying rate decreased, while the other indices increased in the group I compared with the control group (all P<0.05). Compared with the control group, I and II groups, the left atrial volume parameters manifested change in the group III and group IV (all P<0.01). Left atrial ejection fraction measured by RT-3DE or LAT, and late diastolic emptying rate were lower in the group IV compared with the group III (all P<0.05). There was no difference in left atrial conduit volume, passive emptying volume, and early diastolic left atrial emptying rate between the group II and group I (all P>0.05). There was a positive correlation between RT-3DE and LAT in evaluating left atrial function. CONCLUSIONS: Left atrial booster pump function decreases in the eccentric hypertrophy pattern. Left atrial conduit function is unchanged in the normal pattern and the concentric remodelling pattern groups. RT-3DE and LAT technology can be used for quantitative evaluation of left atrial volume and function.

Introducing Bayesian thinking to high-throughput screening for false-negative rate estimation.

High-throughput screening (HTS) has been widely used to identify active compounds (hits) that bind to biological targets. Because of cost concerns, the comprehensive screening of millions of compounds is typically conducted without replication. Real hits that fail to exhibit measurable activity in the primary screen due to random experimental errors will be lost as false-negatives. Conceivably, the projected false-negative rate is a parameter that reflects screening quality. Furthermore, it can be used to guide the selection of optimal numbers of compounds for hit confirmation. Therefore, a method that predicts false-negative rates from the primary screening data is extremely valuable. In this article, we describe the implementation of a pilot screen on a representative fraction (1%) of the screening library in order to obtain information about assay variability as well as a preliminary hit activity distribution profile. Using this training data set, we then developed an algorithm based on Bayesian logic and Monte Carlo simulation to estimate the number of true active compounds and potential missed hits from the full library screen. We have applied this strategy to five screening projects. The results demonstrate that this method produces useful predictions on the numbers of false negatives.

Combining multiple serum biomarkers in tumor diagnosis: A clinical assessment.

The present study aimed to assess the diagnostic/prognostic value of various clinical tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 (CYFRA21-1), α-fetoprotein (AFP), carbohydrate antigen-125 (CA-125), carbohydrate antigen-19.9 (CA-19.9) and ferritin, individually or in combination. The electro-chemiluminescence immunization method was performed to detect the levels of seven tumor markers in 560 cancer patients and 103 healthy subjects for comparison. The serum levels of the seven markers measured in cancer patients were higher compared to healthy subjects (P<0.05 for AFP and P<0.001 for the remaining six markers). Different markers had different sensitivity towards different types of tumors. Combining more markers significantly increased the ratios of positive diagnosis in the tumors. The diagnostic sensitivities of combining seven markers were particularly high in digestive, urinary and skeletal tumors (82, 92 and 83%, respectively). Gynecological tumors have exhibited a constant yet relatively low positive diagnosis irrespective of the use of a single marker or combined markers. However, the increase in sensitivity when combining markers was accompanied by a decrease in specificity. Generally, combining more markers increased the tumor detection rates, while a combination of the seven markers provided the highest detection rate. Combined detection showed a particularly high sensitivity in detecting respiratory, digestive and urinary system tumors, with the lowest sensitivity observed in gynecological tumors. As a result, combining tumor markers may play an important role in early tumor detection/diagnosis while the loss of specificity can be tolerated.

[Post-marketing clinical study of traditional Chinese medicine--lessons learned from comprehensive evaluation of Fufang Zaoren capsule].

By comprehensive review and analysis of post-marketing clinical research on the efficacy and safety,we concluded that Fufang Zaoren capsule has certain therapeutic effects for insomnia, although current clinical research design needs improving. The post-marketing clinical studies also showed that it causes several adverse reactions at the recommended doses, such as chills, fever, dizziness, nausea, shortness of breath, chest tightness and palpitations, whereas high doses of Fufang Zaoren capsule can cause delayed extrapyramidal symptoms. Health Canada government website also prompted the L-tetrahydropalmatine in Fufang Zaoren capsule caused liver damage in pregnant women. The authors summarized the risk points, factors and risk control in the clinical use of Fufang Zaoren capsule and also present their perspective on the research status, existing problems and corresponding countermeasures in the post-marketing clinical re-evaluation of traditional Chinese medicine.

Perioperative corticosteroid reduces hospital stay after fronto-orbital advancement.

Facial swelling is common after fronto-orbital advancement. Edema and closure of the palpebral fissures can lead to prolonged hospitalization. The purpose of this study was to determine if perioperative corticosteroid shortens hospital stay after this procedure.We retrospectively studied consecutive children younger than 2 years who underwent primary fronto-orbital advancement between 1990 and 2008. Patients were categorized into 2 groups: group 1 patients were not given corticosteroid; group 2 patients received tapered perioperative dexamethasone. Primary outcome variables included length of hospital stay and infection rate.A total of 161 patients were included in the study. Hospitalization was significantly shorter (P = 0.008) for group 2 (n = 65; median duration, 3.0 d) than group 1 (n = 96; median duration, 5.0 d). Infection rates did not differ between groups (group 1, 2.1%; group 2, 1.5%; P = 0.8).Perioperative corticosteroid shortens hospitalization after fronto-orbital advancement without increasing the incidence of postoperative infection. The cost of postoperative hospital care was reduced by 27.2%.

An economic approach for construction of a multiplexed capillary electrophoresis system.

We describe in this report an economic approach to construct a multiplexed capillary electrophoresis (CE) system with optic-fiber UV detection. To demonstrate the feasibility of this approach, a seven-lane CE setup is built. The system has a background noise of approximately 10(-5) absorbance unit, a limit of detection of 3-4muM for uracil at 254nm, and a linear dynamic range of 2.5 orders of magnitude. The apparatus consists of three major components: a UV light source, a photodiode array (PDA) and optical module assembly, and a computer. Compared to the recently reported 96-lane capillary electrophoresis system with UV-vis absorbance detection, the cost of goods is reduced by more than 10-fold, and the noise level is improved by 2 to 3 folds. Parallel CE separations of a protein mixture have been performed on this apparatus, and reproducible and high resolution separation results have been obtained. Detailed construction and characterization of the system have also been discussed.