Search Results (126)

The study was conducted to establish the thermoneutral zone (TNZ) of Murrah buffalo calves under precisely regulated environmental conditions. Six healthy calves (8–10 months) were exposed to progressively decreasing (24–15 °C; Temperature-Humidity Index (THI): 72.45–58.98) and increasing (25–40 °C; THI: 73.49–90.32) ambient temperatures with 3 °C intervals in a psychrometric chamber. Each exposure was maintained for 10 consecutive days under cyclic conditions (12 h exposure and 12 h thermoneutral recovery). Physiological responses and body surface temperature (BST) were recorded, and blood samples were collected on day 10 at 1500 h. Segmented regression analysis was performed using the SegReg (Oosterbaan, 2017) software program to identify lower and upper critical temperatures (LCT, UCT) and corresponding THI thresholds. LCTs ranged from 18.06 to 19.14 °C across different responsive parameters, with breakpoints (BPs) at 18.60 °C (SE_BP = 0.634) for pulse rate (PR), 18.15 °C (SE_BP = 0.945) for haemoglobin, 18.15 °C (SE_BP = 0.189) for lymphocytes, 18.24 °C (SE_BP = 0.404) for granulocytes, 19.14 °C (SE_BP = 1.09) for reactive oxygen species (ROS), 18.15 °C (SE_BP = 23.9) for superoxide dismutase (SOD), and 18.06 °C (SE_BP = 4.2) for cortisol; no distinct LCT was detected for respiratory rate (RR), rectal temperature (RT), total leukocyte count (TLC), or heat shock protein (HSP) 70/HSP90 expression. BST at different locations exhibited an LCT between ~20 and 21 °C. UCTs for PR, RR and RT were observed at 28.9 °C (SE_BP = 0.892), 28.6 °C (SE_BP = 0.843) and 29.2 °C (SE_BP = 1.16), respectively. Neither BST nor erythrocytic parameters exhibited a distinct UCT; however, BST increased progressively with increasing exposure temperature. TLC, lymphocyte and granulocyte % showed UCTs of 28.15 °C (SE_BP = 0.753), 28.15 °C (SE_BP = 0.497) and 32.65 °C (SE_BP = 14.20), respectively. The UCT for cortisol was observed at 28.15 °C (SE_BP = 5.52), whereas ROS and SOD showed UCTs of 28.75 °C (SE_BP = 4.67) and 34.15 °C (SE_BP = 6.55), respectively. HSP70 and HSP90 exhibited breakpoints at 35.35 °C (SE_BP = 1.32) and 34.30 °C (SE_BP = 2.11), respectively. Integration of key physiological and systemic responses (excluding BST) indicated a TNZ ranging from 19.14 °C to 28.15 °C. These findings provide a multi-level characterization of thermophysiological responses in buffalo calves and support the use of integrated biological indicators for defining thermoneutral conditions under controlled environments. The estimated TNZ of 19.14–28.15 °C provides a practical reference for managing Murrah buffalo calves. Producers should monitor housing temperature and consider ventilation, shade and air movement when temperatures approach or exceed ~28 °C while providing protection from cold when temperatures fall below ~19 °C. This may help reduce thermal strain and maintain normal physiological function. Full article

Porcine sapelovirus (PSV) is an emerging enteric pathogen associated with diarrheal disease in pigs, yet its epidemiological characteristics and genomic diversity in China remain inadequately characterized. In this study, we systematically compiled epidemic data on all Chinese PSV strains reported in domestic and international literature and constructed a geographic distribution map of PSV across China. Analysis of co-infection patterns revealed that PSV frequently co-occurs with PEDV, PAstV, and PKoV. A total of 74 PSV Chinese strains were retrieved from GenBank for genomic characterization. No distinct regional clustering was observed among the prevalent strains; however, a remarkably high recombination rate of 85.14% was identified, with recombination breakpoints predominantly concentrated near the 2A gene region. Temporal phylogenetic analysis indicated that avian sapeloviruses and PSV shared a similar evolutionary timeline (1985), with PSV-1 emerging earlier than PSV-2. Within the PSV-1 subtype, the German strain exhibited the earliest divergence (1997), followed by Chinese strains (1985), then Korean and American strains (2005). These findings underscore the importance of sustained genomic surveillance and highlight the need for further investigation into the pathogenicity of circulating recombinant strains and their roles in polymicrobial infections, which is critical for developing effective control strategies. Full article

The rise in carbapenem resistance is well documented, but a less conspicuous trend has received far less attention: the gradual upward shift in minimum inhibitory concentration (MIC) values among isolates that remain phenotypically “susceptible.” We propose the term carbapenem floor for this phenomenon: an intermediate zone in which standard dosing regimens become progressively less reliable at achieving target exposure, yet which remains invisible to breakpoint-based surveillance; we present this as a hypothesis-generating framework consistent with existing pharmacokinetic and epidemiological evidence rather than as an empirically established trend, since no systematic longitudinal quantification of carbapenem MIC drift has yet been undertaken. Because carbapenems exhibit time-dependent killing and their pharmacokinetic/pharmacodynamic (PK/PD) target has MIC as its denominator, even a shift within the susceptible range can substantially reduce target attainment; augmented renal clearance in critically ill patients deepens this erosion. This review integrates resistance surveillance evidence with PK/PD principles to evaluate prolonged infusion, loading doses, therapeutic drug monitoring (TDM), and empirical protocols derived from population pharmacokinetic models and local MIC distributions, examining for each the evidence and the practical constraints. We also consider the reverse relationship: failure to attain PK/PD targets appears to select for elevated MICs, suggesting that dosing practice may contribute to resistance selection and potentially influence resistance epidemiology, not only respond to it. Extending antibiogram reporting to include MIC distributions, and translating those data into dosing protocols through antimicrobial stewardship, is a feasible priority where TDM infrastructure is limited. Full article

In response to the escalating challenges of global climate change and extreme meteorological events, this study addresses the critical issue of low disaster resistance in socialist-built heritage (SBH, i.e., built cultural heritage constructed during China’s socialist construction stage from 1949 to 1978). Focusing on Henan Province, China, with meteorological observation datasets spanning 1990–2023 and 1362 SBH sites constructed from 1949 to 1978, we innovatively construct a four-dimensional risk assessment model integrating Meteorological–Environmental Hazard (H), Exposure (E), Vulnerability (V), and Ecological Resilience (R). By synthesizing Spearman correlation analysis, Variance Inflation Factor (VIF) diagnostics, and piecewise regression, this research elucidates the spatial differentiation and driving mechanisms of meteorology-induced compound disaster risks. Key findings identify Zhengzhou and Kaifeng as core high-risk zones and precisely quantify a critical hazard threshold of 0.4 with a 95% breakpoint confidence interval [0.372, 0.428], passing the Chow test p < 0.001 and validated via historical heritage damage records (R² = 0.78). Variable-importance analysis proves that extreme precipitation (32.7%) and annual strong-wind days (28.1%) are the dominant meteorological–environmental drivers, alongside the significant buffering effect of ecological resilience. Ultimately, this study refines the disaster risk assessment framework for SBH, providing robust theoretical support and a decision-making basis for adaptive conservation strategies in similar regions. The average disaster risk of SBH in Henan is 0.421 ± 0.153; for each 0.1 growth of H-E-V coupling term above the threshold of 0.4, disaster risk rises by 37.2%. Full article

Background: Candidozyma auris (C. auris) is an emerging multidrug-resistant yeast associated with healthcare-related transmission, difficult laboratory identification, antifungal resistance, and high mortality in critically ill patients. This study aimed to describe the clinical and microbiological characteristics of early institutional C. auris cases detected in a tertiary hospital in Istanbul, Türkiye. Methods: Adult patients hospitalized between January 2021 and December 2022 with C. auris isolation were retrospectively reviewed. Demographic data, underlying conditions, intensive care unit (ICU) exposure, invasive procedures, antimicrobial and antifungal use, culture sources, antifungal susceptibility testing (AFST) results, and clinical outcomes were evaluated. C. auris isolates were identified using VITEK MS v.3.2, and AFST was performed using C. auris isolates were identified using VITEK MS v.3.2, and AFST was performed using Sensititre YeastOne YO10 (Thermo Fisher Scientific, Waltham, MA, USA) panels. Results were interpreted according to CDC interim breakpoints. Multiple isolates from an individual patient were retained when they represented different specimen types or sampling events. Results: Thirty-three adult patients and 62 clinical isolates were included. The mean age was 67.8 years, and 20 patients (60.6%) were aged 65 years or older. Most patients had prior ICU admission (93.9%), urinary catheterization (97.0%), central venous catheterization (90.9%), mechanical ventilation (81.8%), and broad-spectrum antimicrobial exposure. Blood cultures represented the most frequent source of isolation (56.5%), followed by urine cultures (27.4%). Resistance rates were 98.4% for amphotericin B, 88.7% for fluconazole, 6.6% for micafungin, and 6.5% for caspofungin. Overall mortality was 72.7%. While mortality was numerically higher among patients aged 65 years or older and those requiring inotropic support, only the need for mechanical ventilation was statistically significantly associated with mortality. The cohort-level APACHE II-based expected mortality was 48.0%, whereas observed mortality was 72.7%; this comparison was descriptive and no formal calibration analysis was performed. Conclusions: Early institutional C. auris cases in this tertiary hospital occurred predominantly among elderly, critically ill patients with prolonged healthcare exposure, invasive devices, and extensive antimicrobial use. The findings support the need for early laboratory recognition, cautious interpretation of commercial AFST results, particularly given the propensity of Sensititre YeastOne to overestimate amphotericin B resistance, strengthened infection control practices, and multicenter studies incorporating molecular typing to clarify transmission dynamics and antifungal resistance patterns. Full article

Ecological resilience is a critical indicator of forest ecosystem stability and the capacity to respond to disturbance. Under intensifying climate change and human activities, accurately evaluating forest ecological resilience is important for ecosystem restoration and sustainable management. This study developed a satellite time−series−based framework for assessing ecological resilience from the complementary perspectives of resistance and recovery. Taking the Qianshan region, a typical forest area in the northeastern forest belt, as a case study, MODIS Normalized Difference Vegetation Index (NDVI) time−series data from 2005 to 2024 were analyzed. The Breaks For Additive Season and Trend (BFAST) algorithm was used to detect vegetation breakpoints, after which ecological resistance and recovery were quantified using breakpoint magnitude and post−disturbance NDVI growth rate. The optimal−parameter−based geographical detector (OPGD) was further applied to identify the spatial drivers of resistance and recovery and their interaction effects. Approximately 21% of the pixels in the Qianshan region experienced at least one breakpoint during the study period, and more than 80% of the disturbed pixels contained only one detected breakpoint. More than 70% of the disturbed pixels subsequently exhibited vegetation recovery, and most recovered pixels had normalized recovery values between 0.40 and 1.00. In contrast, ecological resistance was generally low and varied substantially among land−cover types. Forests exhibited higher resistance but lower recovery, whereas grasslands and croplands showed lower resistance but stronger post−disturbance recovery. Among the individual factors, precipitation and slope had relatively high explanatory power for the spatial differentiation of recovery. Factor interactions substantially enhanced explanatory power, with the interaction between precipitation and elevation exerting the strongest influence on resistance and the interaction between precipitation and slope exerting the strongest influence on recovery. Although mining density had relatively limited explanatory power at the regional scale, mining activities caused non−negligible localized impacts, particularly in open−pit mining areas. The proposed framework provides a practical basis for long−term monitoring, ecological restoration, and differentiated forest management in disturbance−prone regions. Full article

Background: Klebsiella pneumoniae is a leading cause of healthcare-associated infections and a major vehicle for the dissemination of antimicrobial resistance (AMR). Romania ranks among the most affected European countries for carbapenem-resistant K. pneumoniae (CRKP), yet data from specialized pulmonology–critical care settings remain limited. Objective: This study aimed to characterize the antimicrobial resistance profiles of K. pneumoniae clinical isolates—including MDR/XDR/PDR classification, carbapenem and colistin resistance rates, specimen and ward distribution, and category-specific resistance patterns—at a tertiary pulmonology–critical care institution in Bucharest, Romania. Methods: A retrospective, single-centre analysis of 203 K. pneumoniae clinical isolates from critical patients, which were collected at the Institute of Pneumology Marius Nasta, Bucharest, between July 2021 and May 2026. Susceptibility testing was performed using the VITEK^®2 system (bioMérieux), with results interpreted per EUCAST breakpoints. Results: Of 203 isolates, 112 (55.2%) were PDR, 36 (17.7%) XDR, six (3.0%) MDR, and 49 (24.1%) non-MDR. Carbapenem resistance was present in 134 isolates (66.0%); colistin resistance was present in 49 of 73 isolates tested (67.1%). Bronchial/tracheal aspirate was the dominant specimen source (61.1%), and intensive care units accounted for 61.1% of isolates. Resistance rates exceeded 75% for monobactams, first/second-generation cephalosporins, and fluoroquinolones. Conclusions: This cohort demonstrates severe AMR burden in this setting, consistent with the most concerning reports for K. pneumoniae in the literature. The findings underscore the urgent need for enhanced antimicrobial stewardship, strengthened infection control in ICU settings, and molecular surveillance of carbapenemase-producing high-risk clonal lineages in Romanian tertiary care. Full article

Background: In catheter-related candidemia, a true catheter-source infection is often difficult to distinguish from a catheter that merely marks critical illness. Our primary aim was to identify predictors of 30-day mortality; secondary aims were to characterize species-specific patterns of persistent candidemia, its prognostic meaning within the host immune–inflammatory context, and the relationship between echinocandin therapy and secondary bacterial bloodstream infection (BSI). Methods: We retrospectively reviewed 89 consecutive episodes of catheter-related candidemia at Bursa City Hospital (2021–2025). Catheter association required Candida spp. growth in concurrent catheter and peripheral blood cultures. The primary endpoint was 30-day mortality; persistent candidemia (≥72 h) and secondary bacterial BSI on days 3–30 were evaluated as exploratory endpoints. Raw MIC values were retrospectively reinterpreted according to EUCAST v12.1 breakpoints (effective 10 April 2026). Results: Thirty-day mortality was 53.9% (48/89). The multivariable model was significant (LR χ² = 12.12, df = 4, p = 0.017; Nagelkerke R² = 0.170); NLR was not significantly associated with mortality (OR = 1.061, 95% CI 1.00–1.13, p = 0.064). Catheter removal, initial echinocandin therapy, and persistent candidemia were not independent predictors, though catheter retention was associated with higher mortality on univariable analysis (83.3%; p = 0.033). Persistent candidemia occurred in 51.7% of episodes, most notably with C. parapsilosis and C. auris. The NLR-persistence interaction was not formally significant, but mortality was higher when both co-occurred (66.7% vs. 36.4%; OR = 3.50, p = 0.075). Secondary BSI occurred in 28.4% of episodes and was more frequent in the echinocandin group (39% vs. 20%; p = 0.062); sensitivity analyses did not change the main findings. Conclusions: Mortality could not be explained by antifungal choice alone; these findings are exploratory. Host response, source control, species distribution, survival time, and device exposure are possible contributing factors warranting evaluation in prospective studies. Full article

The large-scale integration of inverter-interfaced renewable generation has made the steady-state short-circuit current of renewable energy stations increasingly important for setting protections, planning, and fault analysis. Traditional single-unit multiplication methods are computationally efficient but often ignore the effects of internal electrical distance and active power output dispersion among generation units, which can lead to non-negligible errors at the station level. To address this issue, this paper proposes an improved single-unit multiplication method and a corresponding dimension-reduction framework for centralized renewable energy stations considering short-circuit current fitting characteristics. A unified three-segment positive-sequence current control model is first adopted to represent the low-voltage ride-through behavior of photovoltaic (PV), direct-drive wind turbine, and battery energy storage system (BESS) stations. The upper and lower voltage breakpoints are selected as 0.9 p.u. and 0.2 p.u., respectively, and the linear support coefficient was determined as 1.5 according to Chinese national standards. On this basis, the effects of electrical distance and active power output dispersion on the calculation error of the traditional single-unit multiplication method are analyzed. A grouping criterion based on the average access-point voltage and critical active power is then established, and the resulting two-group equivalent method is used to estimate the total short-circuit current of renewable energy stations. Electromagnetic transient simulations in PSCAD are conducted for PV, direct-drive wind, and BESS stations. The results show that, compared with the traditional single-unit multiplication method, the proposed method more accurately captures the steady-state short-circuit current characteristics under different voltage dips and output-dispersion conditions while retaining high engineering practicality. Full article

Rapid urbanization reshapes landscape structure and threatens ecosystem services, yet operational ecological benchmarks for environmental impact assessment remain limited. Focusing on China’s Guanzhong region, this study examines how landscape fragmentation influences the ecosystem service value (ESV) and identifies critical threshold points for planning and management, using land-use data from 1990 to 2020 combined with spatial and statistical analyses. The results show that urban expansion substantially increased landscape fragmentation, with patch density rising by 109%, and contagion declining by 83.7%. Although the total ESV showed partial recovery over the study period, the landscape pattern mediated approximately 62% of the total effect of land-use change on ESV, constituting the dominant transmission pathway. Three actionable thresholds were identified: patch density of 1.2 patches·km⁻², the largest patch index of 18%, and contagion of 15%. Beyond these breakpoints, ESV loss accelerates sharply, with the most pronounced rate increase reaching 355.6%. These findings provide region-specific reference values to support environmental impact assessment, ecological zoning, and land-use regulation in rapidly urbanizing areas. Full article

Objectives: This study aimed to provide an updated overview of metronidazole susceptibility among human clinical isolates of Bacteroides, Phocaeicola, and Parabacteroides in Europe based on EUCAST breakpoint interpretation. Methods: A systematic review and meta-analysis were undertaken following searches of Web of Science, MEDLINE/PubMed, and Embase for studies published between 2011 and 2025. Eligible studies reported metronidazole susceptibility data, including minimum inhibitory concentrations and/or susceptible/resistant proportions, for clinical isolates from European countries. Risk of bias was assessed using criteria adapted from the Joanna Briggs Institute critical appraisal tool. Random-effects meta-analysis of proportions was used to estimate pooled susceptibility, with heterogeneity quantified by I² and τ²; 95% prediction intervals and country subgroup analyses were also performed. Small-study effects were evaluated by funnel plot inspection, Egger’s and Begg’s tests. Results: Thirty-eight studies, comprising 72 country-specific datasets and 8501 isolates, were included. The pooled susceptibility proportion was 99.81% (95% CI 99.44–99.99%), with substantial heterogeneity (I² = 68.2%; τ² = 0.0038). The 95% prediction interval ranged from 95.75% to 100%. Although between-country differences were statistically significant, susceptibility remained consistently high overall. Lower values in Portugal and Switzerland came from single small datasets. Conclusions: These findings support the sustained in vitro activity of metronidazole across Europe, while highlighting the need for continued surveillance, particularly in underrepresented settings. Full article

Background/Objectives: Stenotrophomonas maltophilia is a critical opportunistic pathogen, yet its long-term epidemiology remains underrepresented in global surveillance frameworks like WHO GLASS. We aimed to analyze its six-year epidemiological trend in a large Polish tertiary hospital. Methods: A retrospective study (2020–2025) of 399 non-duplicate isolates was conducted. Identification was performed using MALDI-TOF MS, and susceptibility was analyzed according to EUCAST breakpoints. Antibiotic consumption (DDD/100 patient-days) was correlated with isolation trends. Results: Wound/skin (36.8%) and lower respiratory tract (35.8%) samples predominated. A significant rise in respiratory isolates was observed post-2020, coinciding with peak carbapenem consumption in ICU and surgical wards. Ward-level analysis demonstrated that intensive care unit status (β = 68.9, 95% CI 46.1–91.8, p < 0.001) and carbapenem consumption (β = 0.080, 95% CI 0.004–0.156, p = 0.041) were independently associated with S. maltophilia isolation burden after adjustment for ward type (adjusted R² = 0.80). While trimethoprim–sulfamethoxazole remained highly active, levofloxacin susceptibility showed high interannual variability. Conclusions: S. maltophilia is a stable and clinically significant threat in high-intensity hospital environments. Our findings support the inclusion of this pathogen in international AMR monitoring (GLASS) and emphasize strict carbapenem stewardship to curb its emergence. Full article

As a critical alpine transition zone linking the Qinghai–Tibet Plateau and the Loess Plateau, Gannan Prefecture acts as an important water conservation area in the upper Yellow River basin of China. Based on GLDAS-2.1 surface soil moisture (SSM) datasets spanning 2000–2022 and interpretable machine learning tools (SHAP and ALE), this paper analyzes the spatiotemporal evolution, future trend sustainability, and nonlinear statistical associations between environmental predictors and SSM. The main results were as follows: (1) SSM exhibited a significant upward trend with an annual growth rate of 0.18 kg·m⁻²·a⁻¹ (p < 0.001), and an abrupt turning point occurred in 2017. The spatial pattern of high SSM in the southeast and low SSM in the northwest remained relatively stable, with the centroid migration distance being less than 1.81 km; most regions presented statistically significant moistening trends (p < 0.05). (2) Natural environmental predictors jointly carried 95.79% of the total statistical explanatory weight for modeled SSM variability. Precipitation possessed the highest explanatory proportion (37.93%), followed by temperature (27.30%), potential evapotranspiration (ET_p, 12.26%), elevation (10.44%), and fractional vegetation cover (FVC, 7.77%). One-dimensional ALE curves identified sample-limited statistical breakpoints: SSM gradually plateaued when precipitation reached 650–700 mm, while modeled SSM decreased substantially once ET_p exceeded 800 mm·a⁻¹. Two-dimensional ALE further characterized combined statistical correlations among precipitation, temperature, and ET_p. Model outputs also indicated that FVC above 0.45 corresponded to enhanced soil water retention within the observed sample range, which only reflects statistical patterns captured in this dataset rather than universal regulatory standards. This study offers quantitative statistical understanding of SSM variations across alpine transition zones. Full article

Natural lakes in urbanizing regions face compounding climatic and anthropogenic pressures. Despite their socio-ecological importance, the dual vulnerability of these urban lakes to both long-term areal shrinkage and the shifting frequencies of extreme water events remains a critical research gap, often overlooked in favor of large, remote lake systems. We investigated surface area dynamics, extreme events, and climatic attribution of 7320 natural lakes across China’s five major urban agglomerations (Jing-Jin-Ji, Yangtze River Delta, Greater Bay Area, Chengdu-Chongqing, and Middle Yangtze) from 2001 to 2023. Using a satellite area product, we assessed long-term trends via Seasonal-Trend decomposition by Loess (STL). Regional climate shifts were detected via multi-scale Standardized Precipitation–Evapotranspiration Index (SPEI) breakpoint analysis, and climate attribution was performed by correlating detrended lake areas with SPEI. Results show 59.4% of lakes exhibit significant trends, with shrinkage (50%) vastly outpacing expansion (9.4%), most severely in Jing-Jin-Ji (−0.28%/year). Despite all agglomerations transitioning toward wetter conditions (2008–2013), extreme event responses diverged markedly regionally. Climate-driven lakes (14.5%) displayed stronger shrinkage and greater sensitivity to extremes than lakes with low climate sensitivity, particularly in Jing-Jin-Ji and Chengdu-Chongqing. These findings reveal pronounced spatial heterogeneity in urban lake vulnerability, providing an evidence base for sensitivity-stratified management strategies. Full article

Background/Objectives: Cefiderocol (FDC) is a siderophore-containing cephalosporin that retains activity against many β-lactamase-producing bacteria, such as New Delhi metallo-β-latamase-producing (NDM) K. pneumoniae. Its use in critically ill patients is still limited, since the recommended dosing regimens are mainly derived from studies on healthy subjects, while critical illness is often associated with critical alterations in drug pharmacokinetics. Therefore, the aim of this study was to investigate FDC pharmacokinetic/pharmacodynamic (PK/PD) parameters in real-life patients based on their body weight and renal function. Methods: Patients with K. pneumoniae infections and indications for FDC were enrolled. Drug quantification in plasma was performed at the steady state at different timings. PK/PD targets of fCmin > 4 mg/L (most common) and more stringent targets of fCmin > 8 and 12 mg/L (4× and 6× the EUCAST breakpoint MIC) were considered in relation to patients’ characteristics, 14 days of microbiological eradication and 30-day mortality. Results: Ten patients were enrolled in this study. Mortality, as well as the failure to achieve microbiological eradication, increased with BMI. In a PK/PD point of view, all patients reached the PK/PD targets of fCmin > 4 mg/L and > 8 mg/L, while only 20% reached a fCmin > 12 mg/L, with a key influence of renal function. However, no significant association was found between PK/PD target attainment and treatment outcomes. Conclusions: Our study may be useful for the real-world use of FDC, highlighting the impact of renal function on the achievement of ideal PK/PD thresholds. Nevertheless, the lack of a significant association between PK/PD and outcomes, partially due to the small sample size, highlights the complex impact of patients’ clinical conditions other than drug PK. Full article