Determining climate effects on US total agricultural productivity.

The sensitivity of agricultural productivity to climate has not been sufficiently quantified. The total factor productivity (TFP) of the US agricultural economy has grown continuously for over half a century, with most of the growth typically attributed to technical change. Many studies have examined the effects of local climate on partial productivity measures such as crop yields and economic returns, but these measures cannot account for national-level impacts. Quantifying the relationships between TFP and climate is critical to understanding whether current US agricultural productivity growth will continue into the future. We analyze correlations between regional climate variations and national TFP changes, identify key climate indices, and build a multivariate regression model predicting the growth of agricultural TFP based on a physical understanding of its historical relationship with climate. We show that temperature and precipitation in distinct agricultural regions and seasons explain ∼70% of variations in TFP growth during 1981-2010. To date, the aggregate effects of these regional climate trends on TFP have been outweighed by improvements in technology. Should these relationships continue, however, the projected climate changes could cause TFP to drop by an average 2.84 to 4.34% per year under medium to high emissions scenarios. As a result, TFP could fall to pre-1980 levels by 2050 even when accounting for present rates of innovation. Our analysis provides an empirical foundation for integrated assessment by linking regional climate effects to national economic outcomes, offering a more objective resource for policy making.

FilterNet: A Many-to-Many Deep Learning Architecture for Time Series Classification.

In this paper, we present and benchmark FilterNet, a flexible deep learning architecture for time series classification tasks, such as activity recognition via multichannel sensor data. It adapts popular convolutional neural network (CNN) and long short-term memory (LSTM) motifs which have excelled in activity recognition benchmarks, implementing them in a many-to-many architecture to markedly improve frame-by-frame accuracy, event segmentation accuracy, model size, and computational efficiency. We propose several model variants, evaluate them alongside other published models using the Opportunity benchmark dataset, demonstrate the effect of model ensembling and of altering key parameters, and quantify the quality of the models' segmentation of discrete events. We also offer recommendations for use and suggest potential model extensions. FilterNet advances the state of the art in all measured accuracy and speed metrics when applied to the benchmarked dataset, and it can be extensively customized for other applications.

Integrated Effects of Neonatal Ventral Hippocampal Lesions and Impoverished Social-Environmental Rearing on Endophenotypes of Mental Illness and Addiction Vulnerability.

A wide range of mental illnesses show high rates of addiction comorbidities regardless of their genetic, neurodevelopmental, and/or adverse-environmental etiologies. Understanding how the spectrum of mental illnesses produce addiction vulnerability will be key to discovering more effective preventions and integrated treatments for adults with addiction and dual diagnosis comorbidities. A population of 131 rats containing a spectrum of etiological mental illness models and degrees of severity was experimentally generated by crossing neonatal ventral hippocampal lesions (NVHL; n = 68) or controls (SHAM-operated; n = 63) with adolescent rearing in environmentally/socially enriched (ENR; n = 66) or impoverished (IMP; n = 65) conditions. This population was divided into 2 experiments: first, examining NVHL and IMP effects on novelty and mild stress-induced locomotion across 3 adolescent ages; second, looking at initial cocaine reactivity and long-term cocaine behavioral sensitization in adulthood. NVHL and IMP-environmental conditions independently produced remarkably similar and robustly significant abnormalities of hyperreactivity to novelty, mild stress, and long-term cocaine sensitization. The combined NVHL-IMP groups showed the most severe phenotypes across the board, so that the mental illness and addiction vulnerability phenotypes increased together in severity in a consistent stepwise progression from the healthiest rats to those with the greatest loading of etiological models. These findings add weight to our understanding of mental illness and addiction vulnerability as brain disorders that are biologically and developmentally unified in ways that transcend etiological causes, and yet co-intensify with increased loading of etiological conditions. Combining neurodevelopmental and adverse-environmental models of mental illness may provide an approach to identifying and therapeutically targeting cortical-striatal-limbic network mechanisms that generate addiction and dual diagnosis diseases.

An Innovative Approach to Characterize Clinical ADME and Pharmacokinetics of the Inhaled Drug Nemiralisib Using an Intravenous Microtracer Combined with an Inhaled Dose and an Oral Radiolabel Dose in Healthy Male Subjects.

An innovative open-label, crossover clinical study was used to investigate the excretion balance, pharmacokinetics, and metabolism of nemiralisib-an inhaled phosphoinositide 3-kinase delta inhibitor being developed for respiratory diseases. Six healthy men received a single intravenous microtracer of 10 µg [14C]nemiralisib with a concomitant inhaled nonradiolabeled 1000 µg dose followed by an oral 800 µg dose of [14C]nemiralisib 14 days later. Complementary methods including accelerator mass spectrometry allowed characterization of a range of parameters including oral absorption (Fabs), proportion of nemiralisib escaping gut wall metabolism (Fg), hepatic extraction (Eh), fraction of dose absorbed from inhaled dose (Flung), and renal clearance. Intravenous pharmacokinetics of nemiralisib were characterized by low blood clearance (10.0 l/h), long terminal half-life (55 hours), and high volume of distribution at steady state (728 l). Nemiralisib exhibited moderate inhaled and oral bioavailability (38% and 35%) while Flung was 29%. Absorption and first-pass parameters were corrected for blood renal clearance and compared with values without correction. Any swallowed nemiralisib was relatively well absorbed (Fabs, 0.48) with a high fraction escaping gut wall metabolism and low extraction by the liver (Fg and Eh being 0.83 and 0.10, respectively). There were no major human plasma metabolites requiring further qualification in animal studies. Both unchanged nemiralisib and its oxidative/conjugative metabolites were secreted in bile, with nemiralisib likely subject to further metabolism through enterohepatic recirculation. Direct renal clearance and metabolism followed by renal clearance were lesser routes of elimination. SIGNIFICANCE STATEMENT: A number of innovative features have been combined into one small clinical study enabling a comprehensive description of the human pharmacokinetics and metabolism of an inhaled molecule. Design elements included an intravenous 14C tracer administration concomitant with an inhalation dose that enabled derivation of parameters such as fraction absorbed (Fabs), the proportion of drug escaping first-pass extraction through the gut wall and liver (Fg and Fh) and hepatic extraction (Eh). Entero-test bile sampling enabled characterization of biliary elimination pathways.

Emergency Abdominal Surgery in the Elderly: Can We Predict Mortality?

BACKGROUND: The United Kingdom population is ageing. Half of patients requiring an emergency laparotomy are aged over 70, 20 % die within 30 days, and less than half receive good care. Frailty and delay in management are associated with poor surgical outcomes. P-POSSUM risk scoring is widely accepted, but its validity in patients aged over 70 undergoing emergency laparotomy is unclear. AIMS: To assess if P-POSSUM risk stratification reliably predicts inpatient mortality in this group and establish whether those who died within 30 days received delayed care. METHODS: Observational study of consecutive patients aged 70 and over fulfilling the National Emergency Laparotomy Audit criteria from a tertiary hospital. The predictive value of pre-operative P-POSSUM, ASA, lactate and other routine variables was assessed. Surgical review, decision to operate, consultant surgical review, antibiotic prescription, laparotomy and discharge or death time points were assessed by 30-day survival. RESULTS: One hundred and ninety-three patients were included. This represented 46.28 % of those undergoing an emergency laparotomy in our centre. Pre-operative P-POSSUM scoring, ASA grade and lactate were moderate predictors of mortality (AUC 0.784 and 0.771, respectively, lactate AUC 0.705, all p ≤ 0.001). No correlation existed between pre-operative P-POSSUM and days to death (p = 0.209), nor were there delays in key management timings in those who died in 30 days. CONCLUSIONS: P-POSSUM scoring may predict inpatient mortality with moderate discrimination. Addition of frailty scoring in this high-risk group might better identify those with a high risk of mortality after emergency laparotomy and would be a fertile area for further research.

Assessment of risk behaviors in patients with opioid prescriptions: A study of indiana's inspect data.

BACKGROUND AND OBJECTIVES: Prescription Drug Monitoring Programs (PDMPs) can serve as screening tools and support the clinical decision-making process in patients receiving opioids. The objective of the study was to utilize 2014 INSPECT (Indiana's PDMP) data to identify factors that increase patients' likelihood to engage in opioid-related risk behaviors. METHODS: Based on a literature review, four risk behaviors were identified: Receiving >90 morphine milligram equivalents (MME), having >4 opioid prescribers, obtaining opioids from >4 pharmacies, and concurrent use of opioids and benzodiazepines. Two binary logistic regression analyses (engaging in at least one risk behaviors; engaging in all four risk behaviors) and an ordinal regression analysis (engaging in 0-4 risk behaviors) were conducted to identify factors associated with these opioid-related risk behaviors. RESULTS: Of the 1,538,120 unique opioid patients included in the study, 18.4% engaged in one, 5.3% in two, 1.6% in three, and .4% in all four risk behaviors. Depending on the model, prescribing a second monthly opioid increased patients' odds to engage in risk behaviors by a factor of 10 or more and prescribing two or more benzodiazepines annually increased the odds at least 13-fold. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: About one-fourth of all patients consuming opioids engaged in one or more risk behaviors; higher number of opioid prescriptions and addition of even a small number of benzodiazepine prescriptions dramatically increased these odds. PDMPs can be helpful in identifying opioid users at high-risk for misuse. This information could be used to target efforts to reduce the prescription drug epidemic. (Am J Addict 2017;26:822-829).

Auditory Impairments in HIV-Infected Children.

OBJECTIVES: In a cross-sectional study of human immunodeficiency virus (HIV)-infected adults, the authors showed lower distortion product otoacoustic emissions (DPOAEs) in HIV+ individuals compared with controls as well as findings consistent with a central auditory processing deficit in HIV+ adults on antiretroviral therapy. The authors hypothesized that HIV+ children would also have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. DESIGN: Pure-tone thresholds, DPOAEs, and tympanometry were performed on 244 subjects (131 HIV+ and 113 HIV- subjects). Thirty-five of the HIV+, and 3 of the HIV- subjects had a history of tuberculosis treatment. Gap detection results were available for 18 HIV- and 44 HIV+ children. Auditory brainstem response results were available for 72 HIV- and 72 HIV+ children. Data from ears with abnormal tympanograms were excluded. RESULTS: HIV+ subjects were significantly more likely to have abnormal tympanograms, histories of ear drainage, tuberculosis, or dizziness. All audiometric results were compared between groups using a two-way ANOVA with HIV status and ear drainage history as grouping variables. Mean audiometric thresholds, gap detection thresholds, and auditory brainstem response latencies did not differ between groups, although the HIV+ group had a higher proportion of individuals with a hearing loss >25 dB HL in the better ear. The HIV+ group had reduced DPOAE levels (p < 0.05) at multiple frequencies compared with HIV- subjects. No relationships were found between treatment regimens or delay in starting treatment and audiological parameters. CONCLUSIONS: As expected, children with HIV+ were more likely to have a history of ear drainage, and to have abnormal tympanograms. Similar to the adult findings, the HIV+ group did not show significantly reduced audiometric thresholds, but did have significantly lower DPOAE magnitudes. These data suggest that (1) HIV+ children often have middle ear damage which complicates understanding the direct effects of HIV on the hearing system, and (2) even when corrected for confounders DPOAEs were lower in the HIV+ group. Previous studies suggest ototoxicity from antiretroviral drugs is an unlikely cause of the reduced DPOAE magnitudes. Other possibilities include effects on efferent pathways connecting to outer hair cells or a direct effect of HIV on the cochlea.

Auditory impairments in HIV-infected individuals in Tanzania.

OBJECTIVES: Abnormal hearing tests have been noted in human immunodeficiency virus (HIV)-infected patients in several studies, but the nature of the hearing deficit has not been clearly defined. The authors performed a cross-sectional study of both HIV+ and HIV- individuals in Tanzania by using an audiological test battery. The authors hypothesized that HIV+ adults would have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. In addition, they anticipated that the prevalence of abnormal hearing assessments would increase with antiretroviral therapy (ART) use and treatment for tuberculosis (TB). DESIGN: Pure-tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and a gap-detection test were performed using a laptop-based hearing testing system on 751 subjects (100 HIV- in the United States, plus 651 in Dar es Salaam, Tanzania, including 449 HIV+ [130 ART- and 319 ART+], and 202 HIV-, subjects. No U.S. subjects had a history of TB treatment. In Tanzania, 204 of the HIV+ and 23 of the HIV- subjects had a history of TB treatment. Subjects completed a video and audio questionnaire about their hearing, as well as a health history questionnaire. RESULTS: HIV+ subjects had reduced DPOAE levels compared with HIV- subjects, but their hearing thresholds, tympanometry results, and gap-detection thresholds were similar. Within the HIV+ group, those on ART reported significantly greater difficulties understanding speech in noise, and were significantly more likely to report that they had difficulty understanding speech than the ART- group. The ART+ group had a significantly higher mean gap-detection threshold compared with the ART- group. No effects of TB treatment were seen. CONCLUSIONS: The fact that the ART+/ART- groups did not differ in measures of peripheral hearing ability (DPOAEs, thresholds), or middle ear measures (tympanometry), but that the ART+ group had significantly more trouble understanding speech and had higher gap-detection thresholds indicates a central processing deficit. These data suggest that: (1) hearing deficits in HIV+ individuals could be a CNS side effect of HIV infection, (2) certain ART regimens might produce CNS side effects that manifest themselves as hearing difficulties, and/or (3) some ART regimens may treat CNS HIV inadequately, perhaps due to insufficient CNS drug levels, which is reflected as a central hearing deficit. Monitoring of central hearing parameters could be used to track central effects of either HIV or ART.

Organisation and delivery of a dedicated multidisciplinary prone ventilation team in the intensive care unit: Strategies and lessons from COVID-19.

BACKGROUND: COVID-19 placed immense strain on healthcare systems, necessitating innovative responses to the surge of critically ill patients, particularly those requiring mechanical ventilation. In this report, we detail the establishment of a dedicated critical care prone positioning team at University Hospital Southampton in response to escalating demand for prone positioning during the initial wave of the pandemic. METHODS: The formation of a prone positioning team involved meticulous planning and collaboration across disciplines to ensure safe and efficient manoeuvrers. A comprehensive training strategy, aligned with national guidelines, was implemented for approximately 550 staff members from a diverse background. We surveyed team members to gain insight to the lived experience. RESULTS: A total of 78 full-time team members were recruited and successfully executed over 1200 manoeuvres over an eight-week period. Our survey suggests the majority felt valued and expressed pride and willingness to participate again should the need arise. CONCLUSION: The rapid establishment and deployment of a dedicated prone positioning team may have contributed to both patient care and staff well-being. We provide insight and lessons that may be of value for future respiratory pandemics. Future work should explore objective clinical outcomes and long-term sustainability of such services.

Perioperative management of patients undergoing cytoreductive surgery combined with heated intraperitoneal chemotherapy for peritoneal surface malignancy: a multi-institutional experience.

BACKGROUND: Cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC) is an established treatment for patients with pseudomyxoma peritonei. There is now increasing evidence for the use of CRS and HIPEC in the treatment of other peritoneal surface malignancies. There is currently no consensus on the perioperative management of this patient group. METHODS: An international survey of practice was conducted using an online survey tool. Centers were identified from the list of delegates attending the Seventh International Workshop on Peritoneal Surface malignancy held in Uppsala, Sweden, in September 2010. RESULTS: Fully completed surveys were received from 29 of 41 identified centers (71 %). The survey covers the combined experience amassed by anesthesiologists caring for 8,467 patients undergoing cytoreductive surgery. Intraoperative fluid management, management of coagulopathy, management of the HIPEC phase of the operation, and postoperative analgesia caused the greatest difficulties for the anesthesia team with variation in management identified between different institutions. The incidence of epidural abscess in this patient group was found to be 1:2,139. CONCLUSIONS: Optimal preoperative, intraoperative, and postoperative care is crucial to diminish the complications in this complex treatment strategy. Multicenter collaboration is suggested to gain evidence on the best strategies for perioperative management. Further data collection needs to be undertaken to assess the safety of epidural anesthesia in this patient group.

Effect of PVP on the electroosmotic mobility of wet-etched glass microchannels.

We present an experimental study on the effect of polymer PVP on EOF mobility of microchannels wet etched into optical white soda lime glass, also known as Crown glass. We performed experiments to evaluate the effect of PVP concentration and pH on EOF mobility. We used on-chip capillary zone electrophoresis and a neutral fluorescent dye as a passive marker to quantify the electroosmotic flow. We performed experiments under controlled conditions by varying pH from 5.2 and 10.3 and concentration of PVP from 0 to 2.0% w/w at constant ionic strength (30 mM). Our experiments show that PVP at concentrations of 1.0% or above very effectively suppress EOF at low pH (6.6). At high pH of 10.3, PVP has a much weaker suppressing effect on EOF and increasing its concentration above about 0.5% showed negligible effect on EOF mobility. Finally, we briefly discuss the effects of pH on using PVP as an adsorbed coating. Our experiments provide useful guidelines on choosing correct pH and concentration of PVP for effective EOF suppression in glass channels.

COVID-19 risk, attitudes and behaviour study (CRAB study): A knowledge, attitudes, and practise qualitative study of COVID-19 in the Royal Navy.

Introduction: Outbreaks of SARS-CoV-2 onboard maritime platforms spread rapidly and have high attack rates. The aim of the COVID-19 Risk, Attitudes and Behaviour (CRAB) study was to investigate the knowledge, attitudes, and practises in the Royal Navy in relation to COVID-19 prevention. Methods: The CRAB study was a cross-sectional survey, using a census sampling method, conducted in May and June 2021. An online questionnaire was distributed to all serving Royal Navy regular personnel using either the MyNavy application or via a QR code through email for a continuous 14 day period. The questionnaire was based on an existing validated questionnaire used for avian influenza epidemics. Questions investigated individual perceptions of COVID-19 seriousness, compliance with prevention methods, explored vaccination intention and vaccine hesitancy (unvaccinated individuals who declined or were unsure about receiving a COVID-19 vaccine). The chi-squared test of best fit was used to compare the demographic responses against the whole organisation, with p-value < 0.05 deemed significant. Odds ratios were used to investigate associations between demographic groups and responses to questions, with an odds ratio crossing 1.0 deemed non-significant. Results: The response rate was 6% (2,080/33,200), with 315 responses collated in the pilot phase and 1,765 in the main study phase. Male participants were less likely to rate COVID-19 as serious (OR 0.34; 95% CI: 0.23-0.49). BAME ethnicity (OR 2.41; 95% CI: 1.12-5.17) rated it as more serious. At the time of the study 62% of respondents had received one dose of a COVID-19 vaccine. In the 797 unvaccinated personnel, vaccine hesitancy accounted for 24.2% (193/797), of whom 136 were white males. Those who had a higher COVID-19 serious rating, the most significant factor for non-adherence to COVID-19 prevention measures in both vaccinated (OR 1.61 [95%CI: 1.20-2.17]) and vaccine-hesitant (OR 3.24 [95%CI: 1.63-6.41]) individuals was colleagues' non-adherence. The most trusted source of information on vaccines was provided by the Defence Medical Services (77.2% [1,606/2,080]). Conclusion: This study has identified reasons for COVID-19 protective measure adherence, sources of information trusted by respondents and vaccine hesitancy, in the Royal Navy. The questionnaire can be used to investigate attitudes and behaviours in future emerging infectious diseases.

Aspergillus in COVID-19 intensive care unit; what is lurking above your head?

Introduction: Through routine respiratory samples surveillance among COVID-19 patients in the intensive care, three patients with aspergillus were identified in a newly opened general intensive care unit during the second wave of the pandemic. Methodology: As no previous cases of aspergillus had occurred since the unit had opened. An urgent multidisciplinary outbreak meeting was held. The possible sources of aspergillus infection were explored. The multidisciplinary approach enabled stakeholders from different skills to discuss possible sources and management strategies. Environmental precipitants like air handling units were considered and the overall clinical practice was reviewed. Settle plates were placed around the unit to identify the source. Reports of recent water leaks were also investigated. Results: Growth of aspergillus on a settle plate was identified the potential source above a nurse's station. This was the site of a historic water leak from the ceiling above, that resolved promptly and was not investigated further. Subsequent investigation above the ceiling tiles found pooling of water and mould due to a slow water leak from a pipe. Conclusion: Water leaks in patient areas should be promptly notified to infection prevention. Detailed investigation to ascertain the actual cause of the leak and ensure any remedial work could be carried out swiftly. Outbreak meetings that include diverse people with various expertises (clinical and non-clinical) can enable prompt identification and resolution of contaminated areas to minimise risk to patients and staff. During challenging pandemic periods hospitals must not lose focus on other clusters and outbreaks occurring simultaneously.

Coupled isotachophoretic preconcentration and electrophoretic separation using bidirectional isotachophoresis.

We present a novel technique for coupling isotachophoretic preconcentration and electrophoretic separation using bidirectional isotachophoresis (ITP). Bidirectional ITP simultaneously sets up sharp ITP interfaces between relatively high- and low-mobility cations and high- and low-mobility anions. These two interfaces can migrate toward each other and be described as ion concentration shock waves. We here demonstrate a bidirectional ITP process in which we use the interaction of these anionic and cationic ITP shock waves to trigger a transformation from ITP preconcentration to electrophoretic separation. We use anionic ITP to focus anionic sample species prior to shock interaction. The interaction of the counter-propagating anionic and cationic ITP shocks then changes the local pH (and ionic strength) of the focused analyte zones. Under this new condition, the analytes no longer focus and begin to separate electrophoretically. The method provides faster and much less dispersive transition from ITP preconcentration to electrophoretic separation compared with traditional (unidirectional) transient ITP. It eliminates the need for intermediate steps between focusing and separation, such as manual buffer exchanges. We illustrate the technique with numerical simulations of species transport equations. We have validated our simulations with experimental visualization of bidirectional ITP zones. We then show the effectiveness of the technique by coupling ITP preconcentration and high-resolution separation of a 1 kbp DNA ladder via shock interaction in bidirectional ITP.

Electrophoretic mobility measurements of fluorescent dyes using on-chip capillary electrophoresis.

We present an experimental study of the effect of pH, ionic strength, and concentrations of the electroosmotic flow (EOF)-suppressing polymer polyvinylpyrrolidone (PVP) on the electrophoretic mobilities of commonly used fluorescent dyes (fluorescein, Rhodamine 6G, and Alexa Fluor 488). We performed on-chip capillary zone electrophoresis experiments to directly quantify the effective electrophoretic mobility. We use Rhodamine B as a fluorescent neutral marker (to quantify EOF) and CCD detection. We also report relevant acid dissociation constants and analyte diffusivities based on our absolute estimate (as per Nernst-Einstein diffusion). We perform well-controlled experiments in a pH range of 3-11 and ionic strengths ranging from 30 to 90 mM. We account for the influence of ionic strength on the electrophoretic transport of sample analytes through the Onsager and Fuoss theory extended for finite radii ions to obtain the absolute mobility of the fluorophores. Lastly, we briefly explore the effect of PVP on adsorption-desorption dynamics of all three analytes, with particular attention to cationic R6G.

Deep Learning Classification of Canine Behavior Using a Single Collar-Mounted Accelerometer: Real-World Validation.

Collar-mounted canine activity monitors can use accelerometer data to estimate dog activity levels, step counts, and distance traveled. With recent advances in machine learning and embedded computing, much more nuanced and accurate behavior classification has become possible, giving these affordable consumer devices the potential to improve the efficiency and effectiveness of pet healthcare. Here, we describe a novel deep learning algorithm that classifies dog behavior at sub-second resolution using commercial pet activity monitors. We built machine learning training databases from more than 5000 videos of more than 2500 dogs and ran the algorithms in production on more than 11 million days of device data. We then surveyed project participants representing 10,550 dogs, which provided 163,110 event responses to validate real-world detection of eating and drinking behavior. The resultant algorithm displayed a sensitivity and specificity for detecting drinking behavior (0.949 and 0.999, respectively) and eating behavior (0.988, 0.983). We also demonstrated detection of licking (0.772, 0.990), petting (0.305, 0.991), rubbing (0.729, 0.996), scratching (0.870, 0.997), and sniffing (0.610, 0.968). We show that the devices' position on the collar had no measurable impact on performance. In production, users reported a true positive rate of 95.3% for eating (among 1514 users), and of 94.9% for drinking (among 1491 users). The study demonstrates the accurate detection of important health-related canine behaviors using a collar-mounted accelerometer. We trained and validated our algorithms on a large and realistic training dataset, and we assessed and confirmed accuracy in production via user validation.

Lymphocyte electrotaxis in vitro and in vivo.

Electric fields are generated in vivo in a variety of physiologic and pathologic settings, including penetrating injury to epithelial barriers. An applied electric field with strength within the physiologic range can induce directional cell migration (i.e., electrotaxis) of epithelial cells, endothelial cells, fibroblasts, and neutrophils suggesting a potential role in cell positioning during wound healing. In the present study, we investigated the ability of lymphocytes to respond to applied direct current (DC) electric fields. Using a modified Transwell assay and a simple microfluidic device, we show that human PBLs migrate toward the cathode in physiologically relevant DC electric fields. Additionally, electrical stimulation activates intracellular kinase signaling pathways shared with chemotactic stimuli. Finally, video microscopic tracing of GFP-tagged immunocytes in the skin of mouse ears reveals that motile cutaneous T cells actively migrate toward the cathode of an applied DC electric field. Lymphocyte positioning within tissues can thus be manipulated by externally applied electric fields, and may be influenced by endogenous electrical potential gradients as well.

Recurrent Pneumothorax in a Critically Ill Ventilated COVID-19 Patient.

We present this case of a young woman with SARS-CoV-2 viral infection resulting in coronavirus 2019 (COVID-19) lung disease complicated by a complex hydropneumothorax, recurrent pneumothorax, and pneumatoceles. A 33-year-old woman presented to the hospital with a one-week history of cough, shortness of breath, and myalgia, with no other significant past medical history. She tested positive for COVID-19 and subsequently, her respiratory function rapidly deteriorated, necessitating endotracheal intubation and mechanical ventilation. She had severe hypoxic respiratory failure requiring a protracted period on the mechanical ventilator with different ventilation strategies and multiple cycles of prone positioning. During her proning, after two weeks on the intensive care unit, she developed tension pneumothorax that required bilateral intercostal chest drains (ICD) to stabilise her. After 24 days, she had a percutaneous tracheostomy and began her respiratory wean; however, this was limited due to the ongoing infection. Thorax CT demonstrated a left-sided pneumothorax, with bilateral pneumatoceles and a sizeable, complex hydropneumothorax. Despite the insertion of ICDs, the hydropneumothorax persisted over months and initially progressed in size on serial scans needing multiple ICDs. She was too ill for surgical interventions initially, opting for conservative management. After 60 days, she successfully underwent a video-assisted thoracoscopic surgery (VATS) for a washout and placement of further ICDs. She was successfully decannulated after 109 days on the intensive care unit and was discharged to a rehabilitation unit after 116 days of being an inpatient, with her last thorax CT showing some residual pneumatoceles but significant improvement. Late changes may mean patients recovering from the COVID-19 infection are at increased risk of pneumothoracies. Clinicians need to be alert to this, especially as bullous rupture may not present as a classical pneumothorax.

Conscious prone positioning during non-invasive ventilation in COVID-19 patients: experience from a single centre.

Critically ill patients admitted to hospital following SARS-CoV-2 infection often experience hypoxic respiratory failure and a proportion require invasive mechanical ventilation to maintain adequate oxygenation. The combination of prone positioning and non-invasive ventilation in conscious patients may have a role in improving oxygenation. The purpose of this study was to assess the effect of prone positioning in spontaneously ventilating patients receiving non-invasive ventilation admitted to the intensive care.  Clinical data of 81 patients admitted with COVID 19 pneumonia and acute hypoxic respiratory failure were retrieved from electronic medical records and examined. Patients who had received prone positioning in combination with non-invasive ventilation were identified. A total of 20 patients received prone positioning in conjunction with non-invasive ventilation. This resulted in improved oxygenation as measured by a change in PaO 2/FiO 2 (P/F) ratio of 28.7 mmHg while prone, without significant change in heart rate or respiratory rate. Patients on average underwent 5 cycles with a median duration of 3 hours. There were no reported deaths, 7 of the 20 patients (35%) failed non-invasive ventilation and subsequently required intubation and mechanical ventilation. In our cohort of 20 COVID-19 patients with moderate acute hypoxic respiratory failure, prone positioning with non-invasive ventilation resulted in improved oxygenation. Prone positioning with non-invasive ventilation may be considered as an early therapeutic intervention in COVID-19 patients with moderate acute hypoxic respiratory failure.

Basic principles of electrolyte chemistry for microfluidic electrokinetics. Part I: Acid-base equilibria and pH buffers.

We review fundamental and applied acid-base equilibrium chemistry useful to microfluidic electrokinetics. We present elements of acid-base equilibrium reactions and derive rules for pH calculation for simple buffers. We also present a general formulation to calculate pH of more complex, arbitrary mixtures of electrolytes, and discuss the effects of ionic strength and temperature on pH calculation. More practically, we offer advice on buffer preparation and on buffer reporting. We also discuss "real world" buffers and likely contamination sources. In particular, we discuss the effects of atmospheric carbon dioxide on buffer systems, namely, the increase in ionic strength and acidification of typical electrokinetic device buffers. In Part II of this two-paper series, we discuss the coupling of acid-base equilibria with electrolyte dynamics and electrochemistry in typical microfluidic electrokinetic systems.