Factors Influencing False-Negative Results of QuantiFERON-TB Gold In-Tube (QFT-GIT) in Active Tuberculosis and the Desirability of Resetting Cutoffs for Different Populations: A Retrospective Study

Objectives The value of QuantiFERON-TB Gold In-Tube (QFT-GIT) in the diagnosis of TB varies by population, comorbidities, and other factors. In this study, we aimed to investigate factors that influence false-negative results of QFT-GIT test in the diagnosis of TB as well as the impact of different cutoffs on the diagnostic value. Methods A total of 3562 patients who underwent QFT-GIT tests at Shanghai Pulmonary Hospital were enrolled retrospectively between May 2016 and May 2017. False-negative and false-positive results were analyzed using different clinical stratifications. The optimal cutoff values were established under different clinical conditions. Results Positive QFT-GIT results greatly shortened the time taken to diagnose smear-negative TB. The factors of age, smear and culture results, site of TB, comorbidity with tumors, white blood cell count, neutrophil count, and CD4/CD8 ratio were significantly correlated with false-negative QFT-GIT results (p < 0.05). Personalized cutoff values were established according to different influencing factors. The results showed high consistency between the smear-negative and total populations. Conclusion QFT-GIT can facilitate the early diagnosis of smear-negative TB. The diagnostic performance of the QFT-GIT test in the diagnosis of active TB was shown to be affected by many clinical factors. Personalized cutoff values may have superior value in the identification of active tuberculosis under different conditions

The Impacts of Climate Change on the Hydrological Process and Water Quality in the Three Gorges Reservoir Area, China

With the intensification of climate change, understanding the impacts of climate change on the water cycle is vital for integrated watershed management. Based on the precipitation and temperature data from 1980 to 2018, the climatic change characteristics of the Three Gorges Reservoir Area were analyzed. The Soil and Water Assessment Tool (SWAT) was used to simulate the spatial and temporal distribution of runoff and water quality. The result indicated that precipitation showed clear inter-annual fluctuation, and the maximum and minimum temperatures showed an increasing trend with rates of 0.38 °C/10a and 0.29 °C/10a, respectively. The moving averages revealed that the annual averages of runoff, total nitrogen (TN), and total phosphorus (TP) loads showed a decreasing trend followed by an increasing trend, which experienced strong inter-annual fluctuations. The hydrological processes changed significantly at different spatial scales, and the most affected area was the middle and head of reservoir area. The highest correlation was found between precipitation and runoff (0.91), followed by TP (0.81), and TN (0.60), while extreme precipitation could result in a high probability of water pollution events. These findings provide useful information to support the utilization of water resources, especially in the face of strong climate change impacts

Spatial-temporal variation characteristics and coupling coordination of the “water resources – water environment – water ecology” carrying capacity in the Three Gorges Reservoir Area

The coordinated control and management of water resources, the water environment, and water ecology are essential for optimizing the management of water resources, improving the water environment, rehabilitating water ecosystems, and achieving sustainable development. Most studies conducted to investigate the water carrying capacity have focused primarily on water resources or water environment. However, it is challenging to conduct such research in areas where the interactions between water resources, the environment, and ecology are intricate. In this study, an evaluation indicator system for the water resources - water environment - water ecology carrying capacity (WCC) was constructed, and a coupling coordination model and GeoDetector were employed to systematically analyze the coupling coordination indices (CCI) among the water resource carrying capacity (WRECC), water environment carrying capacity (WENCC), and water ecology carrying capacity (WECCC), as well as the main influencing factors in the Three Gorges Reservoir Area (TGRA) from 2005 to 2018. The results showed that the numbers of counties and districts with a high CCI class gradually increased over this period. The percentage of Class V fluctuated from 0% to 7.7%, and the stability of the water system steadily increased. Spatially, the overall distribution pattern gradually increased from southwest to northeast, and both the single and interactive effects of anthropogenic factors on water systems gradually increased. The CCI was predominantly affected by factors such as the amount of surface water resources per capita, indices of water conservation, forest coverage, discharge of domestic sewage per capita, and water replenishment of the ecosystem. These results show that coordination between the WCC components should be strengthened to further improve water use and domestic water treatment efficiency. To achieve superior-class, effective, and environmentally friendly scientific governance, the productivity of water resources should be increased in areas where the disparity between water availability and the demand for socioeconomic development is severe, and sewage treatment processes should be closely regulated. It is also important to combine resource development and utilization with water ecological protection and management

Heteroleptic Dysprosium(III) Single-Molecule Magnets with Amidinate and Cyclopentadienyl Ligands

Here we use a pseudoallyl ligand, N,N′-chelating amidinate (Am), together with pentamethylcyclopentadienyl (Cp*) to give two dysprosium(III) single-molecule magnets (SMMs): [{(AmiPr)DyCp*(μ-Cl)}2] and [AmdippDyCp*(Cl)(μ-Cl)Li(THF)3] with distinct energy barriers (Ueff) of 97 and 472 K, respectively. The latter Ueff value is similar to the homoleptic Cp*-based Dy-SMM

Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial

In preclinical studies, a new antituberculosis drug regimen markedly reduced the time required to achieve relapse-free cure. This study aimed to preliminarily evaluate the efficacy and safety of this four-month regimen, consisting of clofazimine, prothionamide, pyrazinamide and ethambutol, with a standard six-month regimen in patients with drug-susceptible tuberculosis. An open-label pilot randomized clinical trial was conducted among the patients with newly diagnosed bacteriologically-confirmed pulmonary tuberculosis. The primary efficacy end-point was sputum culture negative conversion. Totally, 93 patients were included in the modified intention-to-treat population. The rates of sputum culture conversion were 65.2% (30/46) and 87.2% (41/47) for short-course and standard regimen group, respectively. There was no difference on two-month culture conversion rates, time to culture conversion, nor early bactericidal activity (P &gt; 0.05). However, patients on short-course regimen were observed with lower rates of radiological improvement or recovery and sustained treatment success, which was mainly attributed to higher percent of patients permanently changed assigned regimen (32.1% vs. 12.3%, P = 0.012). The main cause for it was drug-induced hepatitis (16/17). Although lowering the dose of prothionamide was approved, the alternative option of changing assigned regimen was chosen in this study. While in per-protocol population, sputum culture conversion rates were 87.0% (20/23) and 94.4% (34/36) for the respective groups. Overall, the short-course regimen appeared to have inferior efficacy and higher incidence of hepatitis but desired efficacy in per-protocol population. It provides the first proof-of-concept in humans of the capacity of the short-course approach to identify drug regimens that can shorten the treatment time for tuberculosis

Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial

ABSTRACTIn preclinical studies, a new antituberculosis drug regimen markedly reduced the time required to achieve relapse-free cure. This study aimed to preliminarily evaluate the efficacy and safety of this four-month regimen, consisting of clofazimine, prothionamide, pyrazinamide and ethambutol, with a standard six-month regimen in patients with drug-susceptible tuberculosis. An open-label pilot randomized clinical trial was conducted among the patients with newly diagnosed bacteriologically-confirmed pulmonary tuberculosis. The primary efficacy end-point was sputum culture negative conversion. Totally, 93 patients were included in the modified intention-to-treat population. The rates of sputum culture conversion were 65.2% (30/46) and 87.2% (41/47) for short-course and standard regimen group, respectively. There was no difference on two-month culture conversion rates, time to culture conversion, nor early bactericidal activity (P > 0.05). However, patients on short-course regimen were observed with lower rates of radiological improvement or recovery and sustained treatment success, which was mainly attributed to higher percent of patients permanently changed assigned regimen (32.1% vs. 12.3%, P = 0.012). The main cause for it was drug-induced hepatitis (16/17). Although lowering the dose of prothionamide was approved, the alternative option of changing assigned regimen was chosen in this study. While in per-protocol population, sputum culture conversion rates were 87.0% (20/23) and 94.4% (34/36) for the respective groups. Overall, the short-course regimen appeared to have inferior efficacy and higher incidence of hepatitis but desired efficacy in per-protocol population. It provides the first proof-of-concept in humans of the capacity of the short-course approach to identify drug regimens that can shorten the treatment time for tuberculosis

Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China

Abstract Purpose To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. Methods Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). Results Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32–0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45–0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. Conclusion Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions