Coupled dynamics of voltage and calcium in paced cardiac cells

We investigate numerically and analytically the coupled dynamics of transmembrane voltage and intracellular calcium cycling in paced cardiac cells using a detailed physiological model and its reduction to a three-dimensional discrete map. The results provide a theoretical framework to interpret various experimentally observed modes of instability ranging from electromechanically concordant and discordant alternans to quasiperiodic oscillations of voltage and calcium

Comparison of human uterine cervical electrical impedance measurements derived using two tetrapolar probes of different sizes

BACKGROUND We sought to compare uterine cervical electrical impedance spectroscopy measurements employing two probes of different sizes, and to employ a finite element model to predict and compare the fraction of electrical current derived from subepithelial stromal tissue. METHODS Cervical impedance was measured in 12 subjects during early pregnancy using 2 different sizes of the probes on each subject. RESULTS Mean cervical resistivity was significantly higher (5.4 vs. 2.8 Ωm; p < 0.001) with the smaller probe in the frequency rage of 4–819 kHz. There was no difference in the short-term intra-observer variability between the two probes. The cervical impedance measurements derived in vivo followed the pattern predicted by the finite element model. CONCLUSION Inter-electrode distance on the probes for measuring cervical impedance influences the tissue resistivity values obtained. Determining the appropriate probe size is necessary when conducting clinical studies of resistivity of the cervix and other human tissues

How are hospitals in England caring for women at risk of preterm birth in 2021? The influence of national guidance on preterm birth care in England: a national questionnaire

Background National guidance (Saving Babies Lives Care Bundle Version 2 (SBLCBv2) Element 5) was published in 2019, with the aim to standardise preterm care in England. We plan to identify how many preterm birth surveillance clinics there are in England, and to define current national management in caring for women who are both asymptomatic and high-risk of preterm birth, and who arrive symptomatically in threatened preterm labour, to assist preterm management both nationally and internationally. Methods An online survey comprising of 27 questions was sent to all maternity units in England between February 2021 to July 2021. Results Data was obtained from 96 units. Quantitative analysis and free text analysis was then undertaken. We identified 78 preterm birth surveillance clinics in England, an increase from 30 preterm clinics in 2017. This is a staggering 160% increase in 4 years. SBLCBv2 has had a considerable impact in increasing preterm birth surveillance clinic services, with the majority (61%) of sites reporting that the NHS England publication influenced their unit in setting up their clinic. Variations exist at every step of the preterm pathway, such as deciding which risk factors warrant referral, distinguishing within particular risk factors, and offering screening tests and treatment options. Conclusions While variations in care still do persist, hospitals have done well to increase preterm surveillance clinics, under the difficult circumstances of the COVID pandemic and many without specific additional funding

Intrapulmonary Pharmacokinetics of First-line Anti-tuberculosis Drugs in Malawian Patients With Tuberculosis

BACKGROUND: Further work is required to understand the intrapulmonary pharmacokinetics of first-line anti-tuberculosis drugs. This study aimed to describe the plasma and intrapulmonary pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol, and explore relationships with clinical treatment outcomes in patients with pulmonary tuberculosis. METHODS: Malawian adults with a first presentation of microbiologically-confirmed pulmonary tuberculosis received standard 6-month first-line therapy. Plasma and intrapulmonary samples were collected 8 and 16 weeks into treatment and drug concentrations measured in plasma, lung/airway epithelial lining fluid, and alveolar cells. Population pharmacokinetic modelling generated estimates of drug exposure (Cmax and AUC) from individual-level post-hoc Bayesian estimates of plasma and intrapulmonary pharmacokinetics. RESULTS: One-hundred-and-fifty-seven patients (58% HIV co-infected) participated. Despite standard weight-based dosing, peak plasma concentrations of first-line drugs were below therapeutic drug monitoring targets. Rifampicin concentrations were low in all three compartments. Isoniazid, pyrazinamide, and ethambutol achieved higher concentrations in epithelial lining fluid and alveolar cells than plasma. Isoniazid and pyrazinamide concentrations were 14.6 (95% CI: 11.2-18.0) and 49.8-fold (95% CI: 34.2-65.3) higher in lining fluid than plasma respectively. Ethambutol concentrations were highest in alveolar cells (alveolar cells:plasma ratio 15.0, 95% CI 11.4-18.6). Plasma or intrapulmonary pharmacokinetics did not predict clinical treatment response. CONCLUSIONS: We report differential drug concentrations between plasma and the lung. While plasma concentrations were below therapeutic monitoring targets, accumulation of drugs at the site of disease may explain the success of the first-line regimen. The low rifampicin concentrations observed in all compartments lend strong support for ongoing clinical trials of high-dose rifampicin regimens

Ex Ante Impact Assessment of Policies Affecting Land Use, Part A: Analytical Framework

Contemporary policy making calls for scientific support to anticipate the possible consequences of optional policy decisions on sustainable development. This paper presents an analytical framework for ex ante assessment of economic, social, and environmental impacts of policy driven land use changes that can be used as an aid to policy making. The tasks were to (1) link policy scenarios with land use change simulations, (2) link land use change simulations with environmental, social, and economic impacts through indicators, and (3) valuate the impacts in the context of sustainable development. The outcome was a basis for dialogue at the science-policy interface in the process of developing new policies on the European level that impact on land and land use. The analytical approach provides a logical thread for ex ante impact assessment within the context of sustainable development, land use multifunctionality, and land use change and it provides a thorough discussion of achievements and open challenges related to the framework. It concludes with considerations on the potential for using evidence based ex ante assessments in the process of policy development. The paper is complemented by a B-paper providing exemplary results from two applications of the framework: a financial reform scenario of the Common Agricultural Policy of the European Union, and a bioenergy policy scenario for the case of Poland (Helming et al. 2011)

Soil biochemistry and microbial activity in vineyards under conventional and organic management at Northeast Brazil.

The São Francisco Submedium Valley is located at the Brazilian semiarid region and is an important center for irrigated fruit growing. This region is responsible for 97% of the national exportation of table grapes, including seedless grapes. Based on the fact that orgThe São Francisco Submedium Valley is located at the Brazilian semiarid region and is an important center for irrigated fruit growing. This region is responsible for 97% of the national exportation of table grapes, including seedless grapes. Based on the fact that organic fertilization can improve soil quality, we compared the effects of conventional and organic soil management on microbial activity and mycorrhization of seedless grape crops. We measured glomerospores number, most probable number (MPN) of propagules, richness of arbuscular mycorrhizal fungi (AMF) species, AMF root colonization, EE-BRSP production, carbon microbial biomass (C-MB), microbial respiration, fluorescein diacetate hydrolytic activity (FDA) and metabolic coefficient (qCO2). The organic management led to an increase in all variables with the exception of EE-BRSP and qCO2. Mycorrhizal colonization increased from 4.7% in conventional crops to 15.9% in organic crops. Spore number ranged from 4.1 to 12.4 per 50 g-1 soil in both management systems. The most probable number of AMF propagules increased from 79 cm-3 soil in the conventional system to 110 cm-3 soil in the organic system. Microbial carbon, CO2 emission, and FDA activity were increased by 100 to 200% in the organic crop. Thirteen species of AMF were identified, the majority in the organic cultivation system. Acaulospora excavata, Entrophospora infrequens, Glomus sp.3 and Scutellospora sp. were found only in the organically managed crop. S. gregaria was found only in the conventional crop. Organically managed vineyards increased mycorrhization and general soil microbial activity

A high-quality annually laminated sequence from Lake Belau, Northern Germany: Revised chronology and its implications for palynological and tephrochronological studies

The annually laminated record of Lake Belau offers an exceptional opportunity to investigate with high temporal resolution Holocene environmental change, aspects of climate history and human impact on the landscape. A new chronology based on varve counts, 14C-datings and heavy metal history has been established, covering the last 9400 years. Based on multiple varve counting on two core sequences, the easily countable laminated section spans about 7850 varve years (modelled age range c. 9430 to 1630 cal. BP). Not all of the record is of the same quality but approximately 69% of the varves sequence is classified to be of high quality and only c. 5% of low quality. The new chronology suggests dates generally c. 260 years older than previously assumed for the laminated section of the record. The implications for the vegetation and land-use history of the region as well as revised datings for pollen stratigraphical events are discussed. Tephra analysis allowed the identification of several cryptotephra layers. New dates for volcanic eruptions are presented for the Lairg B event (c. 6848 cal. BP, 2s range 6930–6713 cal. BP), the Hekla 4 event (c. 4396 cal. BP, 2s range 4417–4266 cal. BP), and Hekla 3 eruption (c. 3095 cal. BP, 2s range 3120–3068 cal. BP)

Is short-term-variation of fetal-heart-rate a better predictor of fetal acidaemia in labour? A feasibility study

Background Continuous intrapartum fetal monitoring is challenging and its clinical benefits are debated. The project evaluated whether short-term-variation (STV) and other computerised fetal heart rate (FHR) parameters (baseline FHR, long-term-variation, accelerations and decelerations) predicted acidaemia at birth. The aims of the study were to assess the changes in FHR pattern during labour and determine the feasibility of undertaking a definitive trial by reporting the practicalities of using the monitoring device, participant recruitment, data collection and staff training. Methods 200 high-risk women carrying a term singleton, non-anomalous fetus, requiring continuous FHR monitoring in labour were consented to participate from the Jessop Wing maternity unit, Sheffield, UK. The trans-abdominal fetal ECG monitor was placed as per clinical protocol. During the monitoring session, clinicians were blinded to the computerised FHR parameters. We analysed the last hour of the FHR and its ability to predict umbilical arterial blood pH <7.20 using receiver operator characteristics (ROC) curves. Results Of 200 women, 137 cases were excluded as either the monitor did not work from the onset of labour (n = 30), clinical staff did not return or used the monitor on another patient (n = 37), umbilical cord blood not obtained (n = 25), FHR data not recorded within an hour of birth (n = 34) and other reasons (n = 11). In 63 cases included in the final analysis, the computer-derived FHR parameters did not show significant correlation with umbilical artery cord pH <7.20. Labour was associated with a significant increase in short and long term variation of FHR and number of deceleration (P<0.001). However, baseline FHR decreased significantly before delivery (P<0.001). Conclusions The project encountered a number of challenges, with learning points crucial to informing the design of a large study to evaluate the potential place of intrapartum computerised FHR parameters, using abdominal fetal ECG monitor before its clinical utility and more widespread adoption can be ascertained

Cerebral function parameters in people with HIV switching integrase inhibitors: a randomized controlled trial

Background: Different antiretroviral therapies (ARTs) may have differing effects on central nervous system (CNS) function. We assessed CNS pharmacodynamic effects of switching integrase inhibitors in people-with-HIV (PWH). Methods: PWH on tenofovir-DF/emtricitabine plus raltegravir 400 mg twice daily with suppressed plasma HIV RNA and without overt neuropsychiatric symptoms were randomly allocated on a 1:2 basis to remain on raltegravir or switch to dolutegravir 50 mg once daily for 120 days. Pharmacodynamic parameters assessed included cognitive function (z-score of 7 domains), patient-reported outcome measures (PROMs; PHQ-9 and Beck’s depression questionnaires), cerebral metabolite ratios measured by proton magnetic resonance spectroscopy (H1-MRS) and plasma and cerebrospinal fluid (CSF) HIV RNA. Pharmacokinetic parameters were also assessed in plasma and CSF. Changes and factors associated with changes in pharmacodynamics parameters were assessed. Results: In 20 subjects (19 male, 14 white ethnicity, median age 43 years (IQR: 11.5) and CD4 + count 717 (SD: 298) cells/µL), over 120 days there were no statistically significant changes in cognitive function [mean z-score difference (95%CI) −0.004 (−0.38/0.37); p = 0.98], PROMs [PHQ-9 median score change: 0 in control arm, −0.5 switch arm (p = 0.57); Beck’s depression questionnaire: −1.5 control arm, −1.0 switch arm (p = 0.38)], nor cerebral metabolite ratios between study arms. CSF HIV RNA was <5 copies/mL at baseline and day 120 in all subjects. Geometric mean pre-dose CSF dolutegravir concentration was 7.6 ng/mL (95% CI: 5.2–11.1). Conclusions: Switching integrase inhibitor in virologically suppressed PWH without overt neuropsychiatric symptoms resulted in no significant changes in an extensive panel of CNS pharmacodynamics parameters

Análise integrada de sistemas de produção de tomateiro com base em indicadores edafobiológicos.

A análise integrada de indicadores edafobiológicos ligados ao manejo do solo constitui uma ferramenta importante para estimar níveis de sustentabilidade do agroecossistema, detectando-se pontos críticos para a devida correção de manejo. Essa ferramenta foi empregada na avaliação de sistemas de produção orgânica e convencional de tomate, em cultivo protegido e a campo aberto, no estado de São Paulo. Tomaram-se como referência solos de mata nativa e/ou pastagem natural, dependendo do local de estudo. Em Serra Negra, o solo sob sistema orgânico apresentou maior capacidade de campo e teor de argila dispersa mais baixo, indicativos da estabilidade dos agregados. No sistema convencional observou-se uma elevada condutividade elétrica, evidenciando a alta disponibilidade de sais solúveis. A análise de componentes principais (ACP) permitiu concluir que há maior grau de similaridade entre o solo sob sistema orgânico e aqueles das bases referenciais, com respeito aos indicadores químicos e biológicos. Constatou-se que C org, N total, polissacarídeos, FDA (hidrólise de diacetato de fluoresceína) e atividade enzimática de desidrogenase estão positivamente relacionados com o sistema orgânico, a mata nativa e a pastagem. Em contrapartida, a saturação por bases (V%), pH, teores de Mn, Mg e Ca, bem como a razão de dispersão estão inversamente relacionadas ao manejo orgânico. Já em Araraquara, os resultados da ACP distinguiram as áreas organicamente cultivadas das matas nativas, principalmente, com base nos indicadores biológicos