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Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen‐agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator‐led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling. Here, we investigated whether plerixafor could be repurposed to treat sepsis or severe wound infections, either alone or as an adjunct therapy. In a Pseudomonas aeruginosa lipopolysaccharide (LPS)‐induced zebrafish sepsis model, plerixafor reduced sepsis mortality and morbidity assessed by tail edema. There was a U‐shaped response curve with the greatest effect seen at 0.1 μM concentration. We used Acinetobacter baumannii infection in a neutropenic murine thigh infection model. Plerixafor did not show reduced bacterial growth at 24 h in the mouse thigh model, nor did it amplify the effects of a rifampin antibiotic therapy, in varying regimens. While plerixafor did not mitigate or treat bacterial wound infections in mice, it did reduce sepsis mortality in zebra fish. The observed mortality reduction in our LPS model of zebrafish was consistent with prior research demonstrating a mortality benefit in a murine model of sepsis. However, based on our results, plerixafor is unlikely to be successful as an adjunct therapy for wound infections. Further research is needed to better define the scope of plerixafor as a pathogen‐agnostic therapy. Future directions may include the use of longer acting CXCR4 antagonists, biased CXCR4 signaling, and optimization of animal models. [ABSTRACT FROM AUTHOR]

Substance use is a growing problem in Nigeria. The present study extended recent work documenting the importance of parenting as protective against substance use in Nigerian youth by testing a model linking parenting, additional protective factors and polysubstance use. Public school students (N = 1607; 56% female; M age = 14.88; SD =.44 years) living in the greater Lagos region participated in school‐based data collection. Lifetime polysubstance use, defined as use of two or more substances including alcohol or illicit drugs, or misuse of over‐the‐counter medications, was reported by 5.2% of the sample. Structural equation modelling that accounted for adolescent age and sex on all constructs revealed good model fit. Positive parenting (support and solicitation) was significantly associated with higher perceived harmfulness of substance use, religiosity and positive relationships at school. Positive school relationships were associated with a decreased likelihood of polysubstance use. Multiple group analysis revealed no overall sex differences in the model paths. Strengthening parent–adolescent relationships may have a cascading effect on protective factors and subsequent substance use, and should be included in youth substance use prevention programmes. [ABSTRACT FROM AUTHOR]

1H‐magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single‐voxel MRS (point‐resolved single‐voxel spectroscopy sequence, 1.5 T: echo time [TE] 23–37 ms/135–144 ms, repetition time [TR] 1500 ms; 3 T: TE 37–41 ms/135–144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann–Whitney U‐tests and Kruskal–Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours. [ABSTRACT FROM AUTHOR]

Boundary dynamics are crucial for the transport of energy, mass, and momentum in geospace. The recently discovered plasmapause surface wave (PSW) plays a key role in the inner magnetosphere dynamics. However, a comprehensive investigation of spatial variations of the PSW remains absent. In this study, we elucidate the spatial characteristics of a PSW through observations from multiple spacecrafts in the magnetosphere. Following the initiation of the PSW, quasi‐periodic injections of energetic ions, rather than electrons, are suggested to serve as energy source of the PSW. Based on the distinct wave and particle signatures, we categorize the PSW into four regions: seed region, growth region, stabilization region and decay region, spanning from nightside to afternoon plasmapause. These findings advance our understanding of universal boundary dynamics and contribute to a deeper comprehension of the pivotal roles of surface waves in the energy couplings within the magnetosphere‐plasmasphere‐ionosphere system. Plain Language Summary: Much like the rhythmic beating of a drum, boundaries within the terrestrial system, which delimit distinct plasmas with varying temperatures and densities, can oscillate due to external impulses or internal instabilities, giving rise to surface waves. These surface waves travel along the boundary surface and establish standing wave structures in magnetic field lines. In the terrestrial space environment, two types of surface waves have been identified: the magnetopause surface wave and the plasmapause surface wave (PSW). These waves typically have frequencies ranging from fractions of milli Hertz to a few milli Hertz, with periods spanning from several to tens of minutes. They are believed to play a vital role in mass, energy, and momentum transport within Earth's magnetosphere. However, the exact source that excites the waves and the manner in which the waves evolve along the boundary remain elusive. In this study, we, for the first time, unveil the spatial evolutionary signatures of the PSW during a moderate geomagnetic storm accompanied by substorms, utilizing data from six magnetospheric spacecrafts positioned near the plasmapause. This research contributes to a better understanding of the physical mechanisms underlying the widespread existence of surface waves in the universe, shedding light on the processes of magnetosphere‐plasmasphere‐ionosphere energy couplings and wave‐particle interactions associated with surface waves. Key Points: Spatial characteristics of plasmapause surface wave (PSW) are elucidate with multiple‐spacecraft observations in the magnetosphereIt is suggested that quasi‐periodic injections of energetic ions rather than electrons sustain the PSW during the substormThe PSW is categorized into seed region, growth region, stabilization region, and decay region with different wave and particle properties [ABSTRACT FROM AUTHOR]

Patients with neuroendocrine tumours located in the gastroenteropancreatic tract (GEP‐NETs) and treatment with somatostatin analogues (SSA's) are at risk of malnutrition which has been reported previously evaluating weight loss or body mass index (BMI) only. The global leadership into malnutrition (GLIM) criteria include weight loss, BMI, and sarcopenia, for diagnosing malnutrition. These GLIM criteria have not been assessed in patients with GEP‐NETs on SSA. The effect of malnutrition on overall survival has not been explored before. The aim of this study is to describe the presence of malnutrition in patients with GEP‐NET on SSA based on the GLIM criteria and associate this with overall survival. Cross‐sectional study screening all patients with GEP‐NETs on SSA's for malnutrition using the GLIM criteria. Body composition analysis for sarcopenia diagnosis were performed. Bloods including vitamins, minerals, and lipid profile were collected. Overall survival since the date of nutrition screening was calculated. Uni‐ and multivariate Cox regression analysis were performed to identify malnutrition as risk factor for overall survival. A total of 118 patients, 47% male, with median age 67 years (IQR 56.8–75.0) were included. Overall, malnutrition was present in 88 patients (75%); based on low BMI in 26 (22%) patients, based on weight loss in 35 (30%) patients, and based on sarcopenia in 83 (70%) patients. Vitamin deficiencies were present for vitamin D in 64 patients (54%), and vitamin A in 29 patients (25%). The presence of malnutrition demonstrated a significantly worse overall survival (p‐value =.01). In multivariate analysis meeting 2 or 3 GLIM criteria was significantly associated with worse overall survival (HR 2.16 95% CI 1.34–3.48, p‐value =.002). Weight loss was the most important risk factor out of the 3 GLIM criteria (HR 3.5 95% CI 1.14–10.85, p‐value =.03) for worse overall survival. A high percentage (75%) of patients with GEP‐NETs using a SSA meet the GLIM criteria for malnutrition. Meeting more than 1 GLIM criterium, especially if there is weight loss these are risk factors for worse overall survival. [ABSTRACT FROM AUTHOR]

The interaction of a solar wind discontinuity with the backstreaming particles of the Earth's ion foreshock can generate hot, tenuous plasma transients such as foreshock bubbles (FB) and hot flow anomalies (HFA). These transients are known to have strong effects on the magnetosphere, distorting the magnetopause (MP), either locally during HFAs or globally during FBs. However, previous studies on the global impact of FBs have not been able to determine whether the response stems directly from the transverse scale size of the phenomenon or its fast motion over the magnetosphere. Here we present the observation of an FB and its impact on the magnetosphere from different spacecraft scattered over the dayside magnetosphere. We are able to constrain the size of the transverse scale of an FB from direct observations to be about 10 RE. We go on to discuss how the magnetosphere responds to this transient, which seems to have a similar scale across the dayside. Plain Language Summary: The solar wind is a fast plasma flow of charged particles originating from the Sun. Earth's magnetic field diverts this flow around the planet forming the magnetosphere. The bow shock forms upstream of Earth to decelerate the solar wind and deflect the flow around Earth's magnetic field. A fraction of the solar wind particles are reflected back into the solar wind stream, forming the foreshock. Discontinuities in the solar wind can concentrate these backstreaming particles forming a bubble of hot and tenuous plasma called a foreshock bubble. These transients structures move with the solar wind, arriving at and modifying the bow shock and leading to an expansion of the magnetosphere due to lower pressure within the transients' core. Such a response was reported before in different studies which conclude that foreshock bubbles have a global impact on the magnetosphere. In our study we report on another foreshock bubble observed by a multi‐spacecraft constellation. The observations allowed us to constrain the size of the foreshock bubble. We observe that the large scale response of the magnetosphere seems to reflect with the size of the FB. Key Points: Multi satellite observation of a large foreshock bubble (FB) hitting Earth's magnetosphereThe transverse (y − z) scale size of the FB can be constrained from observations to be at least 8–10 RE fitting with simulationsThe magnetospheric response to the FB seems to be visible across almost 10 RE of the dayside, matching the FB size [ABSTRACT FROM AUTHOR]

The colloidal synthesis of CdSe/ZnSe core/shell quantum dots (QDs) under nitrogen gas flow is presented in this study. The optical, morphology and structural properties of CdSe/ZnSe core/shell QDs are varied by changing the growth temperature and the cadmium source (Cd2+). The Fourier transform infra‐red studies validate that CdSe/ZnSe QDs capped with functional −COOH groups were formed. The morphological and composition studies conducted using high resolution transmission microscope, selected area electron diffraction andenergy dispersive spectroscope confirmed the formation of pure and mono‐disperse QDs while photoluminescence and ultra‐violet visible spectroscopy displayed their improved fluorescent properties. Caco‐2 cell line was cultured from colon cancer and cytotoxic studies were conducted to test for cell viability of various capped 3‐MPA CdSe/ZnSe QDs at various concentrations. The formed CdSe/ZnSe QDs prominently bear the zinc‐blende structure with their particle size lying well below the Bohr excitation radii. Their hydrophilic nature and the availability of functional groups on the CdSe/ZnSe QDs makes them excellent potential labeling and therapeutic agents for the colon cancer disease diagnosis. [ABSTRACT FROM AUTHOR]

Global ultra‐low frequency (ULF) oscillations are believed to play a significant role in the mass, energy, and momentum transport within the Earth's magnetosphere. In this letter, we observe a ∼1.2 mHz radial standing wave in the dusk‐sector magnetosphere accompanied by the field line resonance (FLR) on 16 July 2017. The frequency estimation from the simple box model also confirms the radial standing wave. The essential characteristics of FLR are concurrently identified at the dusk‐sector magnetosphere and the conjugated ground location. Further, the radial standing wave dissipates energy into upper atmosphere to enhance the local aurora by coupling itself to the FLR. The magnetospheric dominant 1.2/1.1 mHz ULF waves plausibly correspond well with the discrete ∼1 mHz magnetosheath ion dynamic pressure/velocity oscillation, suggesting this radial standing wave and FLR in the flank magnetosphere may be triggered by the solar‐wind and/or magnetosheath dynamic pressure/velocity fluctuations. Plain Language Summary: Just like thumping the strings, the Earth's magnetic field line can also be disturbed by the external impulses or internal instability, generating the rich ultra‐low frequency (ULF) oscillations with period of 1–1,000 s. They are believed to play a significant role in the mass, energy, and momentum transport within the Earth's magnetosphere. But the question of how an external driving mechanism can produce field line disturbances deep inside the magnetosphere is a topic of much debate. One classical global mode resonance model suggests that the magnetospheric space sometimes acts as a huge closed or semi‐closed cavity, where the ULF waves form the radial standing wave structure. So far, the observational evidence of radial standing waves with period of above 8 min accompanied by the field line disturbance in the flank magnetosphere is sparse. In this letter, we report a radial standing wave with period of ∼14 min within dusk‐sector magnetosphere accompanied by the field line disturbance phenomenon by multiple‐satellite observations. The radial standing wave energy sinks down to upper atmosphere to light the local aurora by coupling itself to the field line resonance. We conclude the radial standing wave may be caused by the solar‐wind and/or magnetosheath dynamic pressure/velocity fluctuations. Key Points: A radial standing Pc5‐6 ultra‐low frequency wave is identified within the dusk‐sector magnetosphereRadial standing wave dissipates energy into upper atmosphere by coupling itself to the field line resonanceSolar‐wind and/or magnetosheath dynamic pressure/velocity fluctuations possibly trigger this radial standing wave [ABSTRACT FROM AUTHOR]

To first order, the magnetopause (MP) is defined by a pressure balance between the solar wind and the magnetosphere. The boundary moves under the influence of varying solar wind conditions and transient foreshock phenomena, reaching unusually large and small distances from the Earth. We investigate under which solar wind conditions such extreme MP distortions occur. Therefore, we construct a database of magnetopause crossings (MPCs) observed by the THEMIS spacecraft in the years 2007 to mid‐2022 using a simple Random Forest Classifier. Roughly 7% of the found crossing events deviate beyond reported errors in the stand‐off distance from the Shue et al. (1998, https://doi.org/10.1029/98JA01103) MP model and thus are termed extreme distortions. We find the occurrence of these extreme events in terms of expansion or compression of the MP to be linked to different solar wind parameters, most notably to the IMF magnitude, cone angle, velocity, Alfvén Mach number and temperature. Foreshock transients like hot‐flow anomalies and foreshock bubbles could be responsible for extreme magnetospheric expansions. The results should be incorporated into future magnetopause models and may be helpful for the reconstruction of the MP locations out of soft x‐ray images, relevant for the upcoming SMILE mission. Key Points: More than 160.000 magnetopause crossings (MPCs) identified in THEMIS data between 2007 and 2022 using a Random Forest ClassifierMagnetopause crossings that extremely deviate in location from the Shue et al. (1998, https://doi.org/10.1029/98JA01103) model are quite commonImportant solar wind parameters associated with deviations include the interplanetary magnetic field cone angle, solar wind velocity and Alfvén Mach number [ABSTRACT FROM AUTHOR]

Aims: Comorbidities play a significant role towards the pathophysiology of heart failure with preserved ejection fraction (HFpEF), characterized by abnormal macrovascular function and altered ventricular–vascular coupling. However, our understanding of the role of comorbidities and arterial stiffness in HFpEF remains incomplete. We hypothesized that HFpEF is preceded by a cumulative rise in arterial stiffness as cardiovascular comorbidities accumulate, beyond that associated with ageing. Methods and results: Arterial stiffness was assessed using pulse wave velocity (PWV) in five groups: Group A, healthy volunteers (n = 21); Group B, patients with hypertension (n = 21); Group C, hypertension and diabetes mellitus (n = 20); Group D, HFpEF (n = 21); and Group E, HF with reduced ejection fraction (HFrEF) (n = 11). All patients were aged 70 and above. Mean PWV increased from Groups A to D (PWV 10.2, 12.2, 13.0, and 13.7 m/s, respectively) as vascular comorbidities accumulated independent of age, renal function, haemoglobin, obesity (body mass index), smoking status, and hypercholesterolaemia. HFpEF exhibited the highest PWV and HFrEF displayed near‐normal levels (13.7 vs. 10 m/s, P = 0.003). PWV was inversely related to peak oxygen consumption (r = −0.304, P = 0.03) and positively correlated with left ventricular filling pressures (E/e′) on echocardiography (r = −0.307, P = 0.014). Conclusions: This study adds further support to the concept of HFpEF as a disease of the vasculature, underlined by an increasing arterial stiffness that is driven by vascular ageing and accumulating vascular comorbidities, for example, hypertension and diabetes. Reflecting a pulsatile arterial afterload associated with diastolic dysfunction and exercise capacity, PWV may provide a clinically relevant tool to identify at‐risk intermediate phenotypes (e.g. pre‐HFpEF) before overt HFpEF occurs. [ABSTRACT FROM AUTHOR]

Pancreatic metastases (PMs) from neuroendocrine neoplasms (NENs) are rare but the increased sensitivity of new diagnostic tools such as 68Ga‐DOTATATE PET/CT has resulted in their increased recognition at initial diagnosis or follow‐up. A retrospective analysis of the data of patients from six tertiary referral centres was performed in order to identify the characteristics and the prognostic significance of PMs in patients with NENs. We used a control group of 69 age‐, sex‐ and primary tumour – matched NEN patients from the same cohort with stage IV disease but no PMs. Overall survival (OS) was assessed using the Kaplan–Meier method log‐rank analysis was used to assess the impact of various clinical and histopathological variables in OS. We identified 25 patients (11 females) with PMs with a median age at diagnosis of 60 years. The small intestine was the most common primary (80%) with a prevalence of 4.2% PMs (21/506). Fourteen patients presented with synchronous PMs whereas 11 developed metachronous PMs after a median time of 28 months (range: 7–168 months). Grading was available in 24 patients; 16 patients had G1 tumours, four G2, two atypical lung carcinoid, one typical and one atypical thymic carcinoid. Most patients had other concomitant metastases (12 hepatic, 4 lung and 6 bone) while five patients exhibited peritoneal carcinomatosis. Median OS in the PMs group was not reached compared with 212 months in the control group (95% CI: 26–398). The univariate analysis identified no prognostic factors statistically significantly associated with the OS. In conclusion, PMs are encountered with a low prevalence among NEN patients mostly developing in patients with advanced metastatic disease. The presence of PMs does not seem to be associated with a negative prognostic impact in OS. Aretrospective analysis of the data of 25 patients from 6 tertiary referralcenters showed that pancreatic metastases are encountered with a low prevalenceamong patients with neuroendocrine neoplasms, mostly developing in patientswith advanced metastatic disease. The presence of pancreatic metastases doesnot seem to be associated with a negative prognostic impact in overallsurvival. [ABSTRACT FROM AUTHOR]

Objective: The cardio‐renal benefits of sodium glucose‐like transporter 2 inhibitor (SGLT2i) therapies have been demonstrated in patients with and without type 2 diabetes. However, no studies have explored the long‐term metabolic effects of SGLT2i, combined with dietary carbohydrate restriction. Our primary objective was to describe long‐term changes in weight, energy expenditure, appetite and body composition after 12 months of Dapagliflozin therapy, with carbohydrate restriction, in people with type 2 diabetes and obesity. Our secondary objective was to assess changes in adiponectin and leptin. Method: This was a 12‐month cohort study in a secondary care setting. Participants (n = 18) with type 2 diabetes (T2D) and class 3 obesity underwent baseline indirect calorimetry for determination of 24‐h energy expenditure, body composition, fasting serum leptin and adiponectin levels, and appetitive assessments. Following initiation of Dapagliflozin (and dietary carbohydrate restriction), measurements were repeated at monthly intervals up to 12 months. Results: Mean starting weight of participants was 129.4 kg (SD 25.9), mean BMI 46.1 kg/m2 (SD 8.3) and mean HbA1c 53.9 mmol/mol (14.1). Seventeen participants completed the study; after 12 months of Dapagliflozin and dietary carbohydrate restriction, mean weight loss was 8.1 kg (SD 11.3 kg; p =.009). This was mediated by reduced fat mass (mean loss, 9.9 kg; SD 10.4 kg; p =.002) associated with reduced serum leptin at 12 months (mean reduction 11,254 pg/ml; SD 16,075; p =.011). There were no significant changes in self‐reported appetite, 24‐h energy expenditure or serum adiponectin during follow‐up. Conclusion: In this study, combined Dapagliflozin therapy and carbohydrate restriction in patients with T2D and obesity resulted in a significant reduction of body weight and fat mass at 12 months without any discernible changes in energy expenditure or appetite. These results offer a scientific and clinical rationale to conduct an exploratory trial investigating the effects of a low carbohydrate diet combined with SGLT2 inhibitors in patients with T2D. [ABSTRACT FROM AUTHOR]

We aimed to assess the prognostic impact of tumor‐ and patient‐related parameters in patients with stage I–III small intestinal neuroendocrine tumors (SI‐NETs), who underwent locoregional resective surgery (LRS) with curative intent. We included 229 patients with stage I–III SI‐NETs diagnosed from June 15, 1993, through March 8, 2021, identified using the SI‐NET databases from five European referral centers. Mean ± SD age at baseline was 62.5 ± 13.6 years; 111/229 patients were women (49.3%). All tumors were well‐differentiated; 160 were grade 1 (G1) tumors, 51 were G2, two were G3 and 18 tumors were of unspecified grade (median Ki‐67: 2%, range 1%–50%). One‐hundred and sixty‐three patients (71.2%) had lymph node (LN) involvement. The median number of retrieved lymph nodes was 10 (0–63), whereas the median number of positive LNs was 2 (0–43). After a mean ± SD follow‐up of 54.1 ± 64.1 months, 60 patients experienced disease recurrence at a median (range) of 36.2 (2.5–285.1) months. The 5‐ and 10‐year recurrence‐free survival (RFS) rates were 66.6% and 49.3% respectively. In univariable analysis, there was no difference in RFS and overall survival (OS) between LN‐positive and LN‐negative patients (log‐rank, p =.380 and.198, respectively). However, in stage IIIb patients who underwent mesenteric lymph node dissection (MLND) with a minimum of five retrieved LN (n = 125), five or more LN metastases were associated with shorter RFS (median RFS [95% CI] = 107.4 [0–229.6] vs. 73.7 [35.3–112.1] months; log‐rank, p =.048). In addition, patients with G2 tumors exhibited shorter RFS compared to patients with G1 tumors (median RFS [95% confidence interval (CI)] = 46.9 [36.4–57.3] vs. 120.7 [82.7–158.8] months; log‐rank, p =.001). In multivariable Cox‐regression RFS analysis in stage IIIb patients, the Ki‐67 proliferation index (hazard ratio = 1.08, 95% CI = 1.035–1.131; p <.0001) and the number of LN metastases (hazard ratio = 1.06, 95% CI = 1.001–1.125; p =.047) were independent prognostic factors for RFS. In conclusion, LRS with a meticulous MLND and a minimum number of five harvested LNs appears to be critical in the surgical management of SI‐NET patients with locoregional disease. In patients who underwent LRS and MLND, the Ki‐67 proliferation index and the LN metastases count were independent predictors of RFS. [ABSTRACT FROM AUTHOR]

Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature ageing and early death at a mean age of 14.7 years. At the molecular level, HGPS is caused by a de novo heterozygous mutation in LMNA, the gene encoding A‐type lamins (mainly lamin A and C) and nuclear proteins, which have important cellular functions related to structure of the nuclear envelope. The LMNA mutation leads to the synthesis of a truncated prelamin A protein (called progerin), which cannot undergo normal processing to mature lamin A. In normal cells, prelamin A processing involves four posttranslational processing steps catalysed by four different enzymes. In HGPS cells, progerin accumulates as a farnesylated and methylated intermediate in the nuclear envelope where it is toxic and causes nuclear shape abnormalities and senescence. Numerous efforts have been made to target and reduce the toxicity of progerin, eliminate its synthesis and enhance its degradation, but as of today, only the use of farnesyltransferase inhibitors is approved for clinical use in HGPS patients. Here, we review the main current strategies that are being evaluated for treating HGPS, and we focus on efforts to target the posttranslational processing of progerin. [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in 24‐h energy expenditure (EE), substrate oxidation, and body composition following resistance exercise (RE) and a high protein diet via whey protein supplementation (alone and combined) in healthy older men. Methods: In a pooled groups analysis, 33 healthy older men [(mean ± SE) age: 67 ± 1 years; BMI: 25.4 ± 0.4 kg/m2] were randomized to either RE (2×/week; n = 17) or non‐exercise (n = 16) and either a high protein diet via whey protein supplementation (PRO, 2 × 25 g whey protein isolate/d; n = 17) or control (CON, 2 × 23.75 g maltodextrin/d; n = 16). An exploratory sub‐analysis was also conducted between RE+CON (n = 8) and RE+PRO (n = 9). At baseline and 12 weeks, participants resided in respiration chambers for measurement of 24‐h EE and substrate oxidation and wore an accelerometer for 7 days for estimation of free‐living EE. Results: Resistance exercise resulted in greater increases in fat‐free mass (1.0 ± 0.3 kg), resting metabolic rate [(RMR) 36 ± 14 kcal/d], sedentary EE (60 ± 33 kcal/d), and sleeping metabolic rate [(SMR) 45 ± 7 kcal/d] compared to non‐exercise (p < 0.05); however, RE decreased activity energy expenditure in free‐living (−90 ± 25 kcal/d; p = 0.049) and non‐exercise activity inside the respiration chamber (−1.9 ± 1.1%; p = 0.049). PRO decreased fat mass [(FM) −0.5 ± 0.3 kg], increased overnight protein oxidation (30 ± 6 g/d), and decreased 24‐h protein balance (−20 ± 4 g/d) greater than CON (p < 0.05). RE+PRO decreased FM (−1.0 ± 0.5 kg) greater than RE+CON (p = 0.04). Conclusion: Resistance exercise significantly increased RMR, SMR, and sedentary EE in healthy older men, but not total EE. PRO alone and combined with RE decreased FM and aided body weight maintenance. This study was registered at clinicaltrials.gov as NCT03299972. [ABSTRACT FROM AUTHOR]

The basic triggering mechanism underlying induced seismicity traces back to the mid‐1960s that relied on the process of pore‐fluid pressure diffusion. The last decade has experienced a renaissance of induced seismicity research and data proliferation. An unprecedent opportunity is presented to us to synthesize the robust growth in knowledge. The objective of this article is to provide a concise review of the triggering mechanisms of induced earthquakes with a focus on hydro‐mechanical processes. Four mechanisms are reviewed: pore‐fluid pressure diffusion, poroelastic stress, Coulomb static stress transfer, and aseismic slip. For each, an introduction of the concept is presented, followed by case studies. Diving into these mechanisms sheds light on several outstanding questions. For example, why did some earthquakes occur far from fluid injection or after injection stopped? Our review converges on the following conclusions: (a) Pore‐fluid pressure diffusion remains a basic mechanism for initiating inducing seismicity in the near‐field. (b) Poroelastic stresses and aseismic slip play an important role in inducing seismicity in regions beyond the influence of pore‐fluid pressure diffusion. (c) Coulomb static stress transfer from earlier seismicity is shown to be a viable mechanism for increasing stresses on mainshock faults. (d) Multiple mechanisms have operated concurrently or consecutively at most induced seismicity sites. (e) Carbon dioxide injection is succeeding without inducing earthquakes and much can be learned from its success. Future research opportunities exist in deepening the understanding of physical and chemical processes in the nexus of geoenergy development and fluid motion in the Earth's crust. Plain Language Summary: Earthquakes can be triggered by fluids injected into deep underground. Critical knowledge on how they happened has been accumulating since the mid‐1960s after a magnitude 5 earthquake shook Denver, CO, USA. The main culprit is the pore‐fluid pressure in rocks weakening and reactivating existing faults, which leads to earthquakes. The last decade has experienced a renaissance of fluid triggered seismicity research due to the robust development of oil and gas as well as exploration of geothermal energy. This article reviews four processes that contribute to triggering earthquakes: pore‐fluid pressure from injection weakening faults, poroelastic stresses from injection, stresses from earlier earthquakes, and cumulating stresses from aseismic slip. Discussions are presented to address several outstanding questions, for example, why did some earthquakes occur far from fluid injection or after injection? The review leads to following conclusions. (a) Pore‐fluid pressure diffusion remains important for initiating earthquakes near injection. (b) Poroelastic stresses and aseismic slip contribute to inducing seismicity far from injection. (c) Stresses from earlier earthquakes can increase stresses on mainshock faults. (d) Multiple mechanisms often operate to induce earthquakes. (e) CO2 injection is succeeding without inducing earthquakes and lessons can be learned. Future research opportunities exist in understanding induced earthquake hazards. Key Points: Pore‐fluid pressure diffusion remains a basic mechanism for initiating induced seismicity in the vicinity of fluid injectionPoroelastic stress, Coulomb static stress, and aseismic slip also contribute to triggering seismicity beyond the influence of pressure diffusionResearch opportunities exist in developing fully coupled models and integrating process‐oriented models to study induced seismic hazard [ABSTRACT FROM AUTHOR]

Published data suggest that the type of general anaesthesia used during surgical resection for cancer may impact on patient long-term outcome. However, robust prospective clinical evidence is essential to guide a change in clinical practice. We explored the feasibility of conducting a randomised controlled trial to investigate the impact of total intravenous anaesthesia with propofol vs. inhalational volatile anaesthesia on postoperative outcomes of patients undergoing major cancer surgery. We undertook a randomised, double-blind feasibility and pilot study of propofol total intravenous anaesthesia or volatile-based maintenance anaesthesia during cancer resection surgery at three tertiary hospitals in Australia and the USA. Patients were randomly allocated to receive propofol total intravenous anaesthesia or volatile-based maintenance anaesthesia. Primary outcomes for this study were successful recruitment to the study and successful delivery of the assigned anaesthetic treatment as per randomisation arm. Of the 217 eligible patients approached, 146 were recruited, a recruitment rate of 67.3% (95%CI 60.6-73.5%). One hundred and forty-five patients adhered to the randomised treatment arm, 99.3% (95%CI 96.2-100%). Intra-operative patient characteristics and postoperative complications were comparable between the two intervention groups. This feasibility and pilot study supports the viability of the protocol for a large, randomised controlled trial to investigate the effect of anaesthesia technique on postoperative cancer outcomes. The volatile anaesthesia and peri-operative outcomes related to cancer (VAPOR-C) study that is planned to follow this feasibility study is an international, multicentre trial with the aim of providing evidence-based guidelines for the anaesthetic management of patients undergoing major cancer surgery. [ABSTRACT FROM AUTHOR]

Background and objectives: Red blood cell concentrates (RBCC) are susceptible to bacterial contamination despite cold storage. A reliable evaluation of strategies to minimize the risk of RBCC‐associated bacterial transmission requires the use of suitable reference bacteria. Already existing Transfusion‐Relevant Bacteria Reference Strains (TRBRS) for platelet concentrates fail to grow in RBCC. Consequently, the ISBT TTID, Working Party, Bacterial Subgroup, conducted an international study on TRBRS for RBCC. Materials and methods: Six bacterial strains (Listeria monocytogenes PEI‐A‐199, Serratia liquefaciens PEI‐A‐184, Serratia marcescens PEI‐B‐P‐56, Pseudomonas fluorescens PEI‐B‐P‐77, Yersinia enterocolitica PEI‐A‐105, Yersinia enterocolitica PEI‐A‐176) were distributed to 15 laboratories worldwide for enumeration, identification, and determination of growth kinetics in RBCC at days 7, 14, 21, 28, 35 and 42 of storage after low‐count spiking (10–25 CFU/RBCC). Results: Bacterial proliferation in RBCC was obtained for most strains, except for S. marcescens, which grew only at 4 of 15 laboratories. S. liquefaciens, S. marcescens, P. fluorescens and the two Y. enterocolitica strains reached the stationary phase between days 14 and 21 of RBCC storage with a bacterial concentration of approximately 109 CFU/ml. L. monocytogenes displayed slower growth kinetics reaching 106–107 CFU/ml after 42 days. Conclusion: The results illustrate the importance of conducting comprehensive studies to establish well‐characterized reference strains, which can be a tool to assess strategies and methods used to ameliorate blood safety. The WHO Expert Committee on Biological Standardization adopted the five successful strains as official RBCC reference strains. Our study also highlights the relevance of visual inspection to interdict contaminated RBC units. [ABSTRACT FROM AUTHOR]

Flow through rock fractures is frequently represented using models that correct the cubic law to account for the effects of roughness and contact area. However, the scope of such models is often restricted to relatively smooth aperture fields under small confining stresses. This work studies the link between fracture permeability and fracture geometry under normal loads. Numerical experiments are performed to deform synthesized aperture fields of various correlation lengths and roughness values under normal stress. The results demonstrate that aperture roughness can more than triple for applied stresses up to 50 MPa – exceeding the valid range for roughness in most previously published models. Investigating the relationship between permeability and contact area indicates that the increase in flow obstructions due to the development of new contact points strongly depends on the correlation length of the unloaded aperture field. This study eliminates these dependencies by employing a parameter known as the No‐Flow Fraction (NFF) to capture the effect of flow stagnation zones. With this concept, a new Cubic‐law‐based permeability model is proposed that significantly improves the accuracy of permeability estimations, compared to previous models. For cases, where the NFF is difficult to obtain, we introduce an empirical relationship to estimate the parameter from the aperture roughness. The new models yield permeability estimates accurate to within a factor of 2 of the simulated permeability in over three‐quarters of the 3,000 deformed fractures studied. This compares with typical deviations of at least one order of magnitude for previously published permeability models. Key Points: Permeability of fractures under stress depends strongly on the correlation length of the unloaded aperture fieldNo‐Flow Fraction (NFF) is a better indicator of the impact of contact area on permeability compared to fractional contact areaCorrecting the Cubic law with the NFF parameter results in significantly better permeability estimation [ABSTRACT FROM AUTHOR]

Context: Published studies exploring the metabolic effects of Modified‐Release Hydrocortisone (MR‐HC) replacement in patients with adrenal insufficiency (AI). Objective: To compare metabolic effects of MR‐HC with Standard Glucocorticoid (SG) replacement in adults with AI. Randomized control trials (RCTs) were meta‐analysed; non‐RCT studies described narratively with critical appraisal. Data sources: PubMed/Medline, EMBASE, CINAHL and CENTRAL were searched to identify relevant articles, published before Aug 2019. Study selection: All study types that reported metabolic profile (including anthropometric, glucose and lipid‐related parameters), on patients switched from SG to MR‐HC replacement. Following independent screening from two reviewers, 390 studies were identified, of which 9 studies were included for review (RCT, n = 2; non‐RCT, n = 7). Data extraction: Two independent reviewers assessed each paper for bias and data extraction. Results: Meta‐analysis from RCTs (n = 2), 104 patients were switched from SG to MR‐HC replacement. Combining treatment effects, at 3‐months post‐therapy switch there was significant reduction in body weight (−0.82 kg; 95% CI: −1.24 kg to −0.40 kg; P <.001) and HbA1c (−0.13%; 95% CI: −0.214% to −0.045%; P =.003). In the sub‐group with Diabetes Mellitus (DM), reduction in HbA1C was more pronounced (−0.52%; 95% CI: −0.82% to −0.23%; P <.001). Non‐RCT studies showed improved anthropometric measures and glucose metabolism up to 48‐months following switch from SG to MR‐HC replacement. Conclusions: In adults with AI, replacement with MR‐HC associates with significant improvements in anthropometric measurements and HbA1c compared with SG replacement, particularly those with DM. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence and types of sexual dysfunction in pregnancy.Methods: A cross-sectional facility-based descriptive study among pregnant women attending the prenatal clinic of the Greater Accra Regional Hospital, a large tertiary health facility in Accra, Ghana, from May to June 2018. The inclusion criteria were 18 years or older, singleton pregnancy of 8 gestational weeks or more, and residing with their partner for at least 4 weeks before the study. Face-to-face interviews were conducted among consecutively enrolled women by using the Female Sexual Function Index (FSFI) tool.Results: Overall, 425 women were enrolled. The mean age was 30.8 ± 4.8 years. The mean gestational age was 32.3 ± 7.1weeks (range 9.7-42.0 weeks). The prevalence of sexual dysfunction in pregnancy was 64.9% (95% confidence interval [CI], 60.3%-69.4%) but only 32 (7.5%) women self-reported sexual problems. The predominant types of sexual disorder were desire disorder (377 [88.7%; 95% CI, 85.3%-91.4%] women) and arousal disorder (320 [75.3%; 95% CI, 71.0%-79.2%]).Conclusion: Sexual dysfunction in pregnancy was found to be common, but most pregnant women were not aware that they had it. [ABSTRACT FROM AUTHOR]

We present flow‐through experiments to delineate the processes involved in permeability changes driven by effective stress variations and mineral cement dissolution in porous rocks. CO2‐enriched brine is injected continuously into a tight sandstone under in situ reservoir conditions for 455 hrs. Due to the dolomite cement dissolution, the bulk permeability of the sandstone specimen significantly increases, and two dissolution passages are identified near the fluid inlet by X‐ray CT imaging. Prereaction and postreaction examinations of the effective stress law for permeability suggest that after reaction, the bulk permeability is more sensitive to pore pressure changes and less sensitive to effective stress changes. These observations are corroborated by Scanning Electron Microscopy and X‐ray CT observations. This study deepens our understanding of the effect of mineral dissolution on the effective stress law for permeability, with implications for characterizing subsurface mass and energy transport, particularly during fluid injection/production into/from geologic reservoirs. Plain Language Summary: The effective stress law for permeability describes the pore pressure‐effective stress‐permeability relationships and constitutes an essential law in poroelasticity theory. These relationships may change due to chemical fluid‐mineral reactions that modify the geometry of the fluid flow paths. In this work, we conduct laboratory experiments to investigate the evolution of the effective stress law for permeability in a tight sandstone specimen after acid stimulation. Two dissolution passages, formed due to carbonate mineral dissolution, are identified near the injection inlet by X‐ray CT imaging. These passages significantly increase the postreaction specimen permeability and lower the permeability sensitivity to effective stresses. The dissolution of carbonate minerals further exposes previously covered clay minerals to the pore fluid, resulting in a higher sensitivity of pore fluid pressure changes to the bulk permeability. These results are particularly important for geological operations involving fluid injection or production, such as Carbon Capture (Utilization) and Storage (CC(U)S), fluid production, and injection in geothermal systems, oil/gas production, and gas storage. Key Points: During dolomite dissolution, the specimen's bulk permeability is enhanced, due to the formation of two dissolution passagesPermeability is more sensitive to the pore pressure after dolomite dissolution, likely due to the increasing exposure of clay mineralsPermeability is less sensitive to the effective stress after reaction, due to high resistance to pore closure in the dissolution passages [ABSTRACT FROM AUTHOR]

Several progeroid disorders are caused by deficiency in the endoprotease ZMPSTE24 which leads to accumulation of prelamin A at the nuclear envelope. ZMPSTE24 cleaves prelamin A twice: at the third carboxyl‐terminal amino acid following farnesylation of a –CSIM motif; and 15 residues upstream to produce mature lamin A. The carboxyl‐terminal cleavage can also be performed by RAS‐converting enzyme 1 (RCE1) but little is known about the importance of this cleavage for the ability of prelamin A to cause disease. Here, we found that knockout of RCE1 delayed senescence and increased proliferation of ZMPSTE24‐deficient fibroblasts from a patient with non‐classical Hutchinson‐Gilford progeria syndrome (HGPS), but did not influence proliferation of classical LMNA‐mutant HGPS cells. Knockout of Rce1 in Zmpste24‐deficient mice at postnatal week 4–5 increased body weight and doubled the median survival time. The absence of Rce1 in Zmpste24‐deficient fibroblasts did not influence nuclear shape but reduced an interaction between prelamin A and AKT which activated AKT‐mTOR signaling and was required for the increased proliferation. Prelamin A levels increased in Rce1‐deficient cells due to a slower turnover rate but its localization at the nuclear rim was unaffected. These results strengthen the idea that the presence of misshapen nuclei does not prevent phenotype improvement and suggest that targeting RCE1 might be useful for treating the rare progeroid disorders associated with ZMPSTE24 deficiency. [ABSTRACT FROM AUTHOR]

Formation dry‐out in fracture‐dominated geological reservoirs may alter the fracture space, impair rock absolute permeability, and cause a significant decrease in well injectivity. In this study, we numerically model the dry‐out processes occurring during supercritical CO2 (scCO2) injection into single brine‐filled fractures and evaluate the potential for salt precipitation under increasing effective normal stresses in the evaporative regime. We use an open‐source, parallel finite‐element framework to numerically model two‐phase flow through 2‐D fracture planes with aperture fields taken from naturally fractured granite cores at the Grimsel Test Site in Switzerland. Our results reveal a displacement front and a subsequent dry‐out front in all simulated scenarios, where higher effective stresses caused more flow channeling, higher rates of water evaporation, and larger volumes of salt precipitates. However, despite the larger salt volumes, the permeability impairment was lower at higher effective normal stresses. We conclude that the spatial distribution of the salt, precipitated in fractures with heterogeneous aperture fields, strongly affects the absolute permeability impairment caused by formation dry‐out. The numerical simulations assist in understanding the behavior of the injectivity in fractures and fracture networks during subsurface applications that involve scCO2 injection into brine. Key Points: We numerically model formation dry‐out due to supercritical CO2 injection into a single natural fractureVolume of precipitated salt is not a direct indicator for the absolute permeability reduction of a single fractureSalt precipitation patterns in the fracture space vary significantly with the applied effective normal stress [ABSTRACT FROM AUTHOR]

Anti-HBc screening and nucleic acid testing for hepatitis B viral DNA (HBV DNA) detection in blood donors are not routinely performed in clinical settings in Nigeria. This raises serious concerns for safety of blood at a time that global health standards advocate for transfusion safety. The aim of this research is to investigate if presence of anti-HBc in blood donors is actually associated with occult hepatitis B infection through basic and advanced procedures. Prospective blood donors who were seronegative for HBsAg but sero-positive for anti-HBc (with or without other markers) among the four hundred and seventy enrolled in a cross-sectional study were selected for this study. Samples were further screened for hepatitis B core immunoglobulin M by enzyme-linked immunosorbent assay. Nucleic acid testing was performed for confirmation of occult hepatitis B infection. Anti-HBc was detected in 20 (32.8%) of the sixty-one HBsAg antigen-negative blood donors which constituted 13.0% of the total number of enrolled blood donors. Anti-HBc total-positive differentiation showed eighteen (90.0%) anti-HBc (IgG) and two (10%) anti-HBc (IgM) were detected. Nucleic acid testing showed 5.0% prevalence of occult hepatitis B infection among the anti- HBc-positive blood donors with estimated HBV DNA viral load of 58 IU/ml. Demonstration of 5.0% occult hepatitis B prevalence showed the possibility of post-transfusion hepatitis B infection in transfusion recipients with consequent possible liver damage should hepatitis B surface antigen alone be the continued practice in clinical settings. The inclusion of antibody to hepatitis B core antigen screening in addition to hepatitis B surface antigen marker is an essential step to ensuring optimal blood safety and prevent post-transfusion hepatitis. Key words: anti-HBc, isolated, Occult hepatitis B, risk factor, seropositivity. [ABSTRACT FROM AUTHOR]

Hutchinson–Gilford progeria syndrome (HGPS) is caused by an LMNA mutation that results in the production of the abnormal progerin protein. Children with HGPS display phenotypes of premature aging and have an average lifespan of 13 years. We found earlier that the targeting of the transmembrane protein PLA2R1 overcomes senescence and improves phenotypes in a mouse model of progeria. PLA2R1 is regulating the JAK/STAT signaling, but we do not yet know whether targeting this pathway directly would influence cellular and in vivo progeria phenotypes. Here, we show that JAK1/2 inhibition with ruxolitinib rescues progerin‐induced cell cycle arrest, cellular senescence, and misshapen nuclei in human normal fibroblasts expressing progerin. Moreover, ruxolitinib administration reduces several premature aging phenotypes: bone fractures, bone mineral content, grip strength, and a trend to increase survival in a mouse model of progeria. Thus, we propose that ruxolitinib, an FDA‐approved drug, should be further evaluated as a drug candidate in HGPS therapy. [ABSTRACT FROM AUTHOR]

Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone‐insulin‐like growth factor‐1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH‐dependent and ACTH‐independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included. [ABSTRACT FROM AUTHOR]

Precise and direct two‐dimensional (2D) printing of the incompatible polymer acid–base catalysts and their utility in one‐pot two‐step reactions were shown. Multistep catalytic reactions using incompatible catalysts in a one‐pot reaction cascade requires special methods and materials to isolate the catalysts from each other. In general, this is a tedious process requiring special polymer architectures as the carrier for the catalysts to preserve the activity of otherwise incompatible catalysts. We propose the immobilization of incompatible polymer catalysts, such as polymer acid and base catalysts, on a substrate in variable sizes and amounts by precise 2D printing. The terpolymers with basic (4‐vinylpyridine) and acidic (styrene sulfonic acid) functionalities and methacryloyl benzophenone as a UV cross‐linking unit were used for 2D printing on poly(ethylene terephthalate) (PET). The printed meshes were immersed together in a reaction solution containing (dimethoxymethyl)benzene and ethyl cyanoformate, resulting in a two‐step acid–base catalyzed cascade reaction; that is, deacetalization followed by carbon‐building reaction. The time‐dependent consumption of (dimethoxymethyl)benzene to the intermediate benzaldehyde and the product was monitored, and a kinetic model was developed to investigate the underlying reaction dynamics. The complexity of multistep Wolf–Lamb‐type reactions was generally significantly decreased by using our approach because of the easy polymerization and immobilization procedure. [ABSTRACT FROM AUTHOR]

We report on the successful synthesis of CdSe nanoparticles (NPs) via a facile aqueous approach. Investigation on the effects of various cadmium sources in the precursor solution on the CdSe NPs is discussed. The structural and morphological properties characterized by the X‐ray diffraction (XRD) and scanning electron microscope (SEM) displayed good features of the as‐prepared CdSe NPs. The XRD pattern displayed a pure zinc blende crystal structure for all samples, with the most crystalline sample observed for CdSe NPs prepared using anhydrous cadmium chloride. The estimated crystallite sizes were below 6 nm for all the CdSe NPs samples. Mixed shapes of spherical and nanorods of varying sizes were observed from the SEM images for the as‐prepared NPs prepared using different cadmium sources. The optical studies conducted by photo‐spectroscopy pointed out the CdSe NPs prepared using anhydrous cadmium chloride gave the best optical properties. The emission wavelengths were in the range 565 to 574 nm while the optical band gaps were in the range 2.94 to 3.23 eV for all the as‐prepared CdSe NPs samples. All the samples, however, displayed quantum confinement effects giving room for further fabrication and engineering to suit specific applications in the biological field. The obtained results demonstrated that aqueous phase synthetic route employed in this study could be successfully adopted for production of high‐quality CdSe NPs because of its facile and inexpensive nature. [ABSTRACT FROM AUTHOR]

The nature of the capping ligands used and the strength of their interactions with the surface atoms of the nanoparticles (NPs) impact greatly on the material properties and the stability of the resulting NPs. The structural analysis revealed that all the as‐prepared CdTe NPs samples had a zinc blende crystal structure of different phases. The glutathione and L‐cysteine capped CdTe NPs had the same zinc blende phase (JCPDS no. 75–2086) while thioglycolic acid capped and co‐capped CdTe NPs possessed another zinc blende phase (JCPDS no. 75–2083). The calculated crystallite sizes were in the range 2–26 nm for all the samples. The optical spectroscopy studies showed various properties when different capping ligands were used. The band gap energies for all the as‐prepared CdTe NPs confirmed the results obtained from the X‐ray diffraction. The band gap energies were in the range of 2.39–3.34 eV for all the as‐prepared CdTe NPs. The CdTe NPs were produced from the one pot and simple chemical route using various capping ligands (TGA, GSH and L–Cyst). The material properties of CdTe NPs were tailored by using different capping ligands and this is observed during synthesis as the colour of the NP solution changes with different capping ligands. Change of NP solution indicates the formation of CdTe NPs with various material properties. [ABSTRACT FROM AUTHOR]

Sexual selection may increase population‐level fitness by facilitating the removal of deleterious mutations with pleiotropic effects on competition for fertilizations as well as other fitness components in both sexes. Under inbreeding, this could promote purging selection, that is the removal of deleterious recessive alleles exposed in homozygotes via matings between closely related individuals. Here, in two independent experiments, we found no evidence for short‐term purging of the inbreeding load from severely bottlenecked populations of red flour beetles, Tribolium castaneum. We hypothesize that sexual selection may have dual effects on purging, corresponding to good‐genes versus compatible‐genes mechanisms. Whereas the former should facilitate the removal of inbreeding load from bottlenecked populations, the latter may actually hamper this process while simultaneously limiting inbreeding depression by preventing the expression of deleterious recessives. Sexual reproduction, despite multifold costs, is a predominant mode of reproduction among multicellular organisms. It has been theorized that sex may be maintained across evolutionary time because sexual selection, one of important side effects of sexual reproduction, may increase population‐level fitness by facilitating the removal of deleterious mutations. Under inbreeding, this could promote purging selection, i.e., the removal of deleterious recessive alleles exposed in homozygotes via matings between closely related individuals. However, here, in two independent experiments, we found no evidence for short‐term purging of the inbreeding load from severely bottlenecked populations of red flour beetles, Tribolium castaneum. We hypothesize that sexual selection may have dual effects on purging, corresponding to good‐genes versus compatible‐genes mechanisms. [ABSTRACT FROM AUTHOR]

Maize (Zea mays L) yield increases associated with better usage of N fertilizer, (i.e., increased N use efficiency [NUE]), will require innovative breeding efforts. Genomic selection (GS) for N-use traits (e.g., uptake or utilization efficiency) may speed up the breeding cycle of programs targeting NUE in maize. We evaluated the GS accuracy of 12 N-use traits for training populations (TPs) varying in composition (TC) and size, predicted yield performance under different N fertilizer rates, and investigated the usefulness of GS for NUE in maize breeding programs. A total of 552 maize hybrids were planted under low (0 kg N ha-1) and high N fertilizer (252 kg N ha-1) conditions across 10 environments. Training composition scenarios included T0 (hybrids in which none of the parents were included in the random subset of inbreds), T1 (hybrids in which one of their parents were included in the random subset of inbreds), and T2 (hybrids in which both of their parents were included in the random subset of inbreds). Training population sizes ranged from 10 to 40 or 30 to 90 hybrids, depending on the N-use trait. Across different TC, TP sizes, and N-use traits, GS accuracy ranged from -0.12 to 0.78 and was greatest with larger TP sizes when both parents of untested hybrids appeared in the training and validation sets (T2 hybrids). Moreover, GS accuracy in response to different TC and TP sizes was dependent on the N-use trait. Successful breeding for N stress tolerance or improved yield response to N fertilizer level will require selection of specific N-use traits. [ABSTRACT FROM AUTHOR]

Hutchinson–Gilford progeria syndrome (HGPS) is a lethal premature aging that recapitulates many normal aging characteristics. This disorder is caused by mutation in the LMNA gene leading to the production of progerin which induces misshapen nuclei, cellular senescence, and aging. We previously showed that the phospholipase A2 receptor (PLA2R1) promotes senescence induced by replicative, oxidative, and oncogenic stress but its role during progerin‐induced senescence and in progeria is currently unknown. Here, we show that knockdown of PLA2R1 prevented senescence induced by progerin expression in human fibroblasts and markedly delayed senescence of HGPS patient‐derived fibroblasts. Whole‐body knockout of Pla2r1 in a mouse model of progeria decreased some premature aging phenotypes, such as rib fracture and decreased bone content, together with decreased senescence marker. Progerin‐expressing human fibroblasts exhibited a high frequency of misshapen nuclei and increased farnesyl diphosphate synthase (FDPS) expression compared to controls; knockdown of PLA2R1 reduced the frequency of misshapen nuclei and normalized FDPS expression. Pamidronate, a FDPS inhibitor, also reduced senescence and misshapen nuclei. Downstream of PLA2R1, we found that p53 mediated the progerin‐induced increase in FDPS expression and in misshapen nuclei. These results suggest that PLA2R1 mediates key premature aging phenotypes through a p53/FDPS pathway and might be a new therapeutic target. [ABSTRACT FROM AUTHOR]

Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad‐spectrum antimicrobials. Parenteral ceftriaxone is currently a second‐line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may have altered drug absorption, distribution, metabolism, and elimination. Population pharmacokinetics of ceftriaxone and metronidazole were studied, with the aim of recommending optimal dosing. Eighty‐one patients with SAM (aged 2–45 months) provided 234 postdose pharmacokinetic samples for total ceftriaxone, metronidazole, and hydroxymetronidazole. Ceftriaxone protein binding was also measured in 190 of these samples. A three‐compartment model adequately described free ceftriaxone, with a Michaelis–Menten model for concentration and albumin‐dependent protein binding. A one‐compartment model was used for both metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole predicted to be formed during first‐pass. Simulations showed 80 mg/kg once daily of ceftriaxone and 12.5 mg/kg twice daily of metronidazole were sufficient to reach therapeutic targets. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of moving targets with scanned proton beams is challenging. For motion mitigation, an Active Breathing Coordinator (ABC) can be used to assist breath‐holding. The delivery of pencil beam scanning fields often exceeds feasible breath‐hold durations, requiring high breath‐hold reproducibility. We evaluated the robustness of scanned proton therapy against anatomical uncertainties when treating nonsmall‐cell lung cancer (NSCLC) patients during ABC controlled breath‐hold. Methods: Four subsequent MRIs of five healthy volunteers (3 male, 2 female, age: 25–58, BMI: 19–29) were acquired under ABC controlled breath‐hold during two simulated treatment fractions, providing both intrafractional and interfractional information about breath‐hold reproducibility. Deformation vector fields between these MRIs were used to deform CTs of five NSCLC patients. Per patient, four or five cases with different tumor locations were modeled, simulating a total of 23 NSCLC patients. Robustly optimized (3 and 5 mm setup uncertainty respectively and 3% density perturbation) intensity‐modulated proton plans (IMPT) were created and split into subplans of 20 s duration (assumed breath‐hold duration). A fully fractionated treatment was recalculated on the deformed CTs. For each treatment fraction the deformed CTs representing multiple breath‐hold geometries were alternated to simulate repeated ABC breath‐holding during irradiation. Also a worst‐case scenario was simulated by recalculating the complete treatment plan on the deformed CT scan showing the largest deviation with the first deformed CT scan, introducing a systematic error. Both the fractionated breath‐hold scenario and worst‐case scenario were dosimetrically evaluated. Results: Looking at the deformation vector fields between the MRIs of the volunteers, up to 8 mm median intra‐ and interfraction displacements (without outliers) were found for all lung segments. The dosimetric evaluation showed a median difference in D98% between the planned and breath‐hold scenarios of −0.1 Gy (range: −4.1 Gy to 2.0 Gy). D98% target coverage was more than 57.0 Gy for 22/23 cases. The D1 cc of the CTV increased for 21/23 simulations, with a median difference of 0.9 Gy (range: −0.3 to 4.6 Gy). For 14/23 simulations the increment was beyond the allowed maximum dose of 63.0 Gy, though remained under 66.0 Gy (110% of the prescribed dose of 60.0 Gy). Organs at risk doses differed little compared to the planned doses (difference in mean doses <0.9 Gy for the heart and lungs, <1.4% difference in V35 [%] and V20 [%] to the esophagus and lung). Conclusions: When treating under ABC controlled breath‐hold, robustly optimized IMPT plans show limited dosimetric consequences due to anatomical variations between repeated ABC breath‐holds for most cases. Thus, the combination of robustly optimized IMPT plans and the delivery under ABC controlled breath‐hold presents a safe approach for PBS lung treatments. [ABSTRACT FROM AUTHOR]

A positive linear relationship was found between Al amount released from the injection site until day 80 and Al plasma AUC SB (0-80 d) sb ( I y i = 0.73 I x i + 927; I r i = .79) or bone Al concentration ( I y i = 0.00079 I x i + 0.63; I r i = .70), respectively (Figure S4). Thus, increase in bone Al concentration in a human adult after absorption of a SCIT Al dose of 659 µg (estimated Al release after P2 on day 80) is assumed 1/27 of that observed in our rats. Analysis of aluminium in rat following administration of allergen immunotherapy using either aluminium or microcrystalline-tyrosine-based adjuvants. [Extracted from the article]

Abstract: Background: Various endocrine signals oscillate over the 24‐hour period and so does the responsiveness of target tissues. These daily oscillations do not occur solely in response to external stimuli but are also under the control of an intrinsic circadian clock. Design: We searched the PubMed database to identify studies describing the associations of clock genes with endocrine diseases. Results: Various human single nucleotide polymorphisms of brain and muscle ARNT‐like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) genes exhibited significant associations with type 2 diabetes mellitus. ARNTL2 gene expression and upregulation of BMAL1 and PER1 were associated with the development of type 1 diabetes mellitus. Thyroid hormones modulated PER2 expression in a tissue‐specific way, whereas BMAL1 regulated the expression of type 2 iodothyronine deiodinase in specific tissues. Adrenal gland and adrenal adenoma expressed PER1, PER2, CRY2, CLOCK and BMAL1 genes. Adrenal sensitivity to adrenocorticotrophin was also affected by circadian oscillations. A significant correlation between the expression of propio‐melanocorticotrophin and PER 2, as well as between prolactin and CLOCK, was found in corticotroph and lactosomatotroph cells, respectively, in the pituitary. Clock genes and especially BMAL1 showed an important role in fertility, whereas oestradiol and androgens exhibited tissue‐specific effects on clock gene expression. Metabolic disorders were also associated with circadian dysregulation according to studies in shift workers. Conclusions: Clock genes are associated with various endocrine disorders through complex mechanisms. However, data on humans are scarce. Moreover, clock genes exhibit a tissue‐specific expression representing an additional level of regulation. Their specific role in endocrine disorders and their potential implications remain to be further clarified. [ABSTRACT FROM AUTHOR]

Transitional cell carcinoma (TCC) is the most common neoplasia of the canine urinary tract. It tends to be locally invasive and has a moderate metastatic rate. Receptor tyrosine kinases (RTKs) play an important role in promoting cell growth, differentiation and regulation of cell function. RTK inhibitor toceranib phosphate has been used anecdotally to treat TCC. The goal of this study was to evaluate archived normal urinary bladder, TCC and cystitis bladder samples for expression of toceranib phosphate targets: VEGFR2, PDGFR-β and stem cell factor receptor (KIT). A significant number of TCC samples expressed PDGFR-β compared with cystitis and normal bladder samples (P<.0001). While all the tumour samples stained positively for VEGFR2, there was no significant difference between tumour, cystitis and normal bladder samples in intensity scores or staining distribution. Minimal positive staining for KIT was noted in the tumour samples. Based on this proof of target study, further investigation is warranted to determine clinical response of TCC to toceranib phosphate. [ABSTRACT FROM AUTHOR]

Aims: Overactive bladder (OAB) and benign prostatic hyperplasia (BPH) are highly prevalent conditions that place a large burden on the United States (US) health care system. We sought to analyze patterns of prescription medication usage for incident OAB in men and women, and for incident BPH in men using US health insurance claims data. Materials and Methods: This study used Truven Health MarketScan® Commercial and Medicare Supplemental Research databases. The data were pooled from diverse points of care. BPH subjects included men age 18+ with the first and last two diagnoses of BPH ≥30 days apart and no BPH diagnosis for 1 year prior. OAB subjects included men and women age 18+, who were diagnosed similarly with incident OAB. The type of medication, medication continuation (persistence), and switching to a different medication were analyzed through September 30, 2013. Results: Medication persistence was much higher overall for BPH than OAB (56% vs 34%, respectively, P < 0.0001), and was highest among men with BPH age 65+ (62%). Patients age 18‐64 were less likely to continue medication than older adults (age 65+) for both BPH and OAB. A 9.4% of patients in the OAB cohort and 6.9% of men with BPH switched from one medication to another. Conclusions: Persistence was higher with BPH than OAB medications overall, whereas switching rates were higher in the OAB group. The lower persistence of OAB medication may be due to less efficacy or tolerability. The possibility of under treatment of OAB also warrants future investigations. [ABSTRACT FROM AUTHOR]

Purpose: To propose a method to quantify T1 and contrast agent uptake in breast dynamic contrast‐enhanced (DCE) examinations undertaken with standard clinical fat‐suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas. Methods: A standard fat‐suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)‐weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B0 field inhomogeneity was assessed in test objects and healthy volunteers. The T1 of breast tumors was calculated at different time points (pre‐, peak‐, and post‐contrast agent administration) for 20 patients, pre‐treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank‐sum test). Results: The calibration curves proved to be highly reproducible (coefficient of variation under 10%). T1 measurements were affected by B0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat‐suppressed T1 measurements of breast parenchyma in volunteers. The values of T1 measured pre‐, peak‐, and post‐contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T1 for that range. Significant differences were identified in the width of the distributions of the post‐contrast T1 values between lobular and ductal carcinomas (P < 0.05); lobular carcinomas demonstrated a wider range of post‐contrast T1 values, potentially related to their infiltrative growth pattern. Conclusions: This work has demonstrated the feasibility of fat‐suppressed T1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between lobular and invasive ductal carcinomas, and further enables the optimization of DCE protocols by tailoring the dynamic range of the sequence to the values of T1 measured. [ABSTRACT FROM AUTHOR]

Background The reconstruction of heart valves provides substantial benefits, particularly in the pediatric population. We present our experience using decellularized extracellular matrix ( dECM, CorMatrix®) for aortic valve procedures. Methods We retrospectively reviewed the case histories of 6 patients (aged from 2 months - 14 years) who underwent surgery for severe aortic valve stenosis (n = 4) or regurgitation (n = 2). Aortic valve repair was performed on all patients using dECM as a leaflet replacement or leaflet extension. Follow-ups were performed using echocardiography. Reoperation was necessary in 4 cases, and the dECM was explanted and examined histologically and immunohistochemically. Results The early post-operative period was uneventful, and the scaffold fulfilled the mechanical requirements. Significant valve insufficiency developed in 5 patients during the post-operative period (119-441 days postoperatively). In all specimens, only a migration of inflammatory cells was identified, which induced structural and functional changes caused by the chronic inflammatory response. Conclusions Our results suggest a mixed immunological response of remodeling and inflammation following the implantation. The expected process of seeding/migration and remodeling of the bioscaffold into the typical 3-layered architecture were not observed in our explanted specimens. [ABSTRACT FROM AUTHOR]

Background: Patients treated with intravenous immunoglobulins (IVIG) rarely experience symptomatic hemolysis. Although anti-A and anti-B isoagglutinins from the product are involved in most cases, the actual mechanisms triggering hemolysis are unclear.Study Design and Methods: A prospective, open-label, multicenter, single-arm clinical trial in 57 patients with immune thrombocytopenia treated with IVIG (Privigen, CSL Behring) was conducted.Results: Twenty-one patients received one infusion (1 g/kg) and 36 received two infusions (2 × 1 g/kg) of IVIG. After a study duration of more than 2 years, no cases of clinically significant hemolysis as defined in the protocol were identified. Data of patients with mild hematologic and biochemical changes were analyzed in more detail. Twelve cases (10/23 patients with blood group A1 and 2/11 patients with blood group B, all having received 2 g/kg IVIG) were adjudicated as mild hemolysis (median hemoglobin [Hb] decrease, -3.0 g/dL); Hb decreases were transient, with partial or full recovery achieved by last visit. Eighteen patients (31.6%), all with non-O blood group, of whom 16 (88.9%) received 2 g/kg IVIG, fulfilled post hoc criteria for hemolytic laboratory reactions. Red blood cell (RBC) eluates of all direct antiglobulin test-positive samples were negative for non-ABO blood group antibodies. Blood groups A and B antigen density on RBCs appeared to be a risk factor for hemolytic laboratory reactions. Platelet response to treatment was observed in 42 patients (74%); eight of 12 patients with complete response had blood group A1.Conclusion: Isoagglutinins are involved in clinically nonsignificant hemolysis after treatment with IVIG, but individual susceptibility varies greatly. [ABSTRACT FROM AUTHOR]

Purpose To compare two methods of automatic breast segmentation with each other and with manual segmentation in a large subject cohort. To discuss the factors involved in selecting the most appropriate algorithm for automatic segmentation and, in particular, to investigate the appropriateness of overlap measures (e.g., Dice and Jaccard coefficients) as the primary determinant in algorithm selection. Methods Two methods of breast segmentation were applied to the task of calculating MRI breast density in 200 subjects drawn from the Avon Longitudinal Study of Parents and Children, a large cohort study with an MRI component. A semiautomated, bias-corrected, fuzzy C-means ( BC- FCM) method was combined with morphological operations to segment the overall breast volume from in-phase Dixon images. The method makes use of novel, problem-specific insights. The resulting segmentation mask was then applied to the corresponding Dixon water and fat images, which were combined to give Dixon MRI density values. Contemporaneously acquired T1- and T2-weighted image datasets were analyzed using a novel and fully automated algorithm involving image filtering, landmark identification, and explicit location of the pectoral muscle boundary. Within the region found, fat-water discrimination was performed using an Expectation Maximization-Markov Random Field technique, yielding a second independent estimate of MRI density. Results Images are presented for two individual women, demonstrating how the difficulty of the problem is highly subject-specific. Dice and Jaccard coefficients comparing the semiautomated BC- FCM method, operating on Dixon source data, with expert manual segmentation are presented. The corresponding results for the method based on T1- and T2-weighted data are slightly lower in the individual cases shown, but scatter plots and interclass correlations for the cohort as a whole show that both methods do an excellent job in segmenting and classifying breast tissue. Conclusions Epidemiological results demonstrate that both methods of automated segmentation are suitable for the chosen application and that it is important to consider a range of factors when choosing a segmentation algorithm, rather than focus narrowly on a single metric such as the Dice coefficient. [ABSTRACT FROM AUTHOR]

We recently demonstrated a bilateral projection to the supraoculomotor area from the central mesencephalic reticular formation (cMRF), a region implicated in horizontal gaze changes. C-group motoneurons, which supply multiply innervated fibers in the medial rectus muscle, are located within the primate supraoculomotor area, but their inputs and function are poorly understood. Here, we tested whether C-group motoneurons in Macaca fascicularis monkeys receive a direct cMRF input by injecting this portion of the reticular formation with anterograde tracers in combination with injection of retrograde tracer into the medial rectus muscle. The results indicate that the cMRF provides a dense, bilateral projection to the region of the medial rectus C-group motoneurons. Numerous close associations between labeled terminals and each multiply innervated fiber motoneuron were present. Within the oculomotor nucleus, a much sparser ipsilateral projection onto some of the A- and B- group medial rectus motoneurons that supply singly innervated fibers was observed. Ultrastructural analysis demonstrated a direct synaptic linkage between anterogradely labeled reticular terminals and retrogradely labeled medial rectus motoneurons in all three groups. These findings reinforce the notion that the cMRF is a critical hub for oculomotility by proving that it contains premotor neurons supplying horizontal extraocular muscle motoneurons. The differences between the cMRF input patterns for C-group versus A- and B-group motoneurons suggest the C-group motoneurons serve a different oculomotor role than the others. The similar patterns of cMRF input to C-group motoneurons and preganglionic Edinger-Westphal motoneurons suggest that medial rectus C-group motoneurons may play a role in accommodation-related vergence. [ABSTRACT FROM AUTHOR]

Background: With the ongoing public health emergency due to Zika virus (ZIKV), nucleic acid testing (NAT) is essential for clinical diagnosis and screening of blood donors. However, NAT for ZIKV has not been standardized, and this study was performed to establish a World Health Organization (WHO) International Standard (IS) for ZIKV RNA; WHO ISs have been used to improve detection and quantification of blood-borne viruses.Study Design and Methods: The candidate IS (cIS), code number 11468/16, was prepared by heat inactivation and lyophilization of a ZIKV strain isolated from a patient in French Polynesia in 2013. The cIS was evaluated together with other reference materials, including both Asian and African ZIKV lineages as well as a panel of clinical samples and in vitro-transcribed RNAs. The samples for evaluation were distributed to 24 laboratories from 11 countries. The assays used consisted of a mixture of in-house developed and commercial assays (available or in development).Results: The potencies of the standards were determined by quantitative and qualitative assays. In total, 37 sets of data were analyzed: 19 from quantitative assays and 18 from qualitative assays. Data demonstrated wide variations in reported potencies of the cIS and the other study samples.Conclusions: Assay variability was substantially reduced when ZIKV RNA concentrations from the biological reference materials and clinical samples were expressed relative to the cIS. Thus, the WHO has established 11468/16 as the 1st IS for ZIKV RNA, with a unitage of 50,000,000 IU/mL. [ABSTRACT FROM AUTHOR]

ABSTRACT This study explores two points related to the pattern of innervation of the extraocular muscles. First, species differences exist in the location of the motoneurons supplying multiply innervated fibers (MIFs) and singly innervated fibers (SIFs) in eye muscles. MIF motoneurons are located outside the extraocular nuclei in primates, but are intermixed with SIF motoneurons within rat extraocular nuclei. To test whether this difference is related to visual capacity and frontal placement of eyes, we injected retrograde tracers into the medial rectus muscle of the cat, a highly visual nonprimate with frontally placed eyes. Distal injections labeled smaller MIF motoneurons located ventrolaterally and rostrally within the oculomotor nucleus (III). More central injections also labeled a separate population of larger cells located dorsally in III. Thus, the cat shares with the nocturnal rat the feature of having MIF motoneurons located within the bounds of III. On the other hand, just as with monkeys, cats show segregation of the MIF and SIF medial rectus motoneuron pools, albeit in a different pattern. Second, extraocular muscles are divided into two layers; the inner, global layer inserts into the sclera, and the outer, orbital layer inserts into the connective tissue pulley. To test whether these layers are supplied by anatomically discrete motoneuron pools, we injected tracer into the orbital layer of the cat lateral rectus muscle. No evidence of either morphological or distributional differences was found, suggesting that the functional differences in these layers may be due mainly to their orbital anatomy, not their innervation. J. Comp. Neurol. 525:919-935, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Four reactive flow-through laboratory experiments (two each at 0.1 mL/min and 0.01 mL/min flow rates) at 150°C and 150 bar (15 MPa) are conducted on intact basalt cores to assess changes in porosity, permeability, and surface area caused by CO2-rich fluid-rock interaction. Permeability decreases slightly during the lower flow rate experiments and increases during the higher flow rate experiments. At the higher flow rate, core permeability increases by more than one order of magnitude in one experiment and less than a factor of two in the other due to differences in preexisting flow path structure. X-ray computed tomography (XRCT) scans of pre- and post-experiment cores identify both mineral dissolution and secondary mineralization, with a net decrease in XRCT porosity of ∼0.7%-0.8% for the larger pores in all four cores. (Ultra) small-angle neutron scattering ((U)SANS) data sets indicate an increase in both (U)SANS porosity and specific surface area (SSA) over the ∼1 nm to 10 µm scale range in post-experiment basalt samples, with differences due to flow rate and reaction time. Net porosity increases from summing porosity changes from XRCT and (U)SANS analyses are consistent with core mass decreases. (U)SANS data suggest an overall preservation of the pore structure with no change in mineral surface roughness from reaction, and the pore structure is unique in comparison to previously published basalt analyses. Together, these data sets illustrate changes in physical parameters that arise due to fluid-basalt interaction in relatively low pH environments with elevated CO2 concentration, with significant implications for flow, transport, and reaction through geologic formations. [ABSTRACT FROM AUTHOR]

Abstract: An Active Breathing Coordinator (ABC) can be employed to induce breath‐holds during CT imaging and radiotherapy of lung, breast and liver cancer, and recently during lung cancer MRI. The apparatus measures and controls respiratory volume, hence subject lung volume reproducibility is its principal measure of effectiveness. To assess ABC control quality, the intra‐session reproducibility of ABC‐induced lung volumes was evaluated and compared with that reached by applying the clinical standard of operator‐guided self‐sustained breath‐holds on healthy volunteers during MRI. Inter‐session reproducibility was investigated by repeating ABC‐controlled breath‐holds on a second visit. Additionally, lung volume agreement with ABC devices used with different imaging modalities in the same institution (MR, CT), or for a breast trial treatment, was assessed. Lung volumes were derived from three‐dimensional (3D) T1‐weighted MRI datasets by three observers employing semiautomatic lung delineation on a radiotherapy treatment planning system. Inter‐observer variability was less than 6% of the delineated lung volumes. Lung volume agreement between the different conditions over all subjects was investigated using descriptive statistics. The ABC equipment dedicated for MR application exhibited good intra‐session and inter‐session lung volume reproducibility (1.8% and 3% lung volume variability on average, respectively). MR‐assessed lung volumes were similar using different ABC equipment dedicated to MR, CT, or breast radiotherapy. Overall, lung volumes controlled by the same or different ABC devices agreed better than with self‐controlled breath‐holds, as suggested by the average ABC variation of 1.8% of the measured lung volumes (99 mL), compared to the 4.1% (226 mL) variability observed on average with self‐sustained breath‐holding. [ABSTRACT FROM AUTHOR]