The enduring world forest carbon sink.

The uptake of carbon dioxide (CO2) by terrestrial ecosystems is critical for moderating climate change1. To provide a ground-based long-term assessment of the contribution of forests to terrestrial CO2 uptake, we synthesized in situ forest data from boreal, temperate and tropical biomes spanning three decades. We found that the carbon sink in global forests was steady, at 3.6 ± 0.4 Pg C yr-1 in the 1990s and 2000s, and 3.5 ± 0.4 Pg C yr-1 in the 2010s. Despite this global stability, our analysis revealed some major biome-level changes. Carbon sinks have increased in temperate (+30 ± 5%) and tropical regrowth (+29 ± 8%) forests owing to increases in forest area, but they decreased in boreal (-36 ± 6%) and tropical intact (-31 ± 7%) forests, as a result of intensified disturbances and losses in intact forest area, respectively. Mass-balance studies indicate that the global land carbon sink has increased2, implying an increase in the non-forest-land carbon sink. The global forest sink is equivalent to almost half of fossil-fuel emissions (7.8 ± 0.4 Pg C yr-1 in 1990-2019). However, two-thirds of the benefit from the sink has been negated by tropical deforestation (2.2 ± 0.5 Pg C yr-1 in 1990-2019). Although the global forest sink has endured undiminished for three decades, despite regional variations, it could be weakened by ageing forests, continuing deforestation and further intensification of disturbance regimes1. To protect the carbon sink, land management policies are needed to limit deforestation, promote forest restoration and improve timber-harvesting practices1,3.

Evolution in Laparoscopic Gastrectomy From a Randomized Controlled Trial Through National Clinical Practice.

OBJECTIVE: To examine the influence of the LOGICA RCT (randomized controlled trial) upon the practice and outcomes of laparoscopic gastrectomy within the Netherlands. BACKGROUND: Following RCTs the dissemination of complex interventions has been poorly studied. The LOGICA RCT included 10 Dutch centers and compared laparoscopic to open gastrectomy. METHODS: Data were obtained from the Dutch Upper Gastrointestinal Cancer Audit (DUCA) on all gastrectomies performed in the Netherlands (2012-2021), and the LOGICA RCT from 2015 to 2018. Multilevel multivariable logistic regression analyses were performed to assess the effect of laparoscopic versus open gastrectomy upon clinical outcomes before, during, and after the LOGICA RCT. RESULTS: Two hundred eleven patients from the LOGICA RCT (105 open vs 106 laparoscopic) and 4131 patients from the DUCA data set (1884 open vs 2247 laparoscopic) were included. In 2012, laparoscopic gastrectomy was performed in 6% of patients, increasing to 82% in 2021. No significant effect of laparoscopic gastrectomy on postoperative clinical outcomes was observed within the LOGICA RCT. Nationally within DUCA, a shift toward a beneficial effect of laparoscopic gastrectomy upon complications was observed, reaching a significant reduction in overall [adjusted odds ratio (aOR):0.62; 95% CI: 0.46-0.82], severe (aOR: 0.64; 95% CI: 0.46-0.90) and cardiac complications (aOR: 0.51; 95% CI: 0.30-0.89) after the LOGICA trial. CONCLUSIONS: The wider benefits of the LOGICA trial included the safe dissemination of laparoscopic gastrectomy across the Netherlands. The robust surgical quality assurance program in the design of the LOGICA RCT was crucial to facilitate the national dissemination of the technique following the trial and reducing potential patient harm during surgeons learning curve.

[Medical practice in classical Greece : The neurological and psychiatric case reports of the Hippocratic Corpus]. / Medizinische Praxis im klassischen Griechenland : Die neurologischen und psychiatrischen Fallberichte des Corpus Hippocraticum.

OBJECTIVE: Which theoretical and practical competences do the neurological and psychiatric case histories of the Hippocratic Corpus convey? MATERIAL AND METHODS: The 431 Hippocratic case histories have been studied for reports and communication on the diagnostics, treatment and prognosis of single persons and groups of patients suffering from neurological and psychiatric diseases. RESULTS: In the 7 books of the Hippocratic Epidemics, a total of 128 patients with neurological and psychiatric symptoms are described. Epidemic fever and its variants were the leading predisposing conditions and the main symptoms were delirium, coma, insomnia, headache, speech disorders and convulsions. A number of patients with phrenitis and opisthotonos are also reported. The majority of the sick persons were male, were teenagers or adults and 47 of them are mentioned by name. The patient's information about the course is often just as informative as the doctor's observations. Treatment was limited to physical and dietary measures. DISCUSSION: The Hippocratic physician diagnosed and attempted to treat a large number of neurological and psychiatric diseases. The often almost continuous observations of the patients led to astonishingly precise predictions of the course and the prospects of recovery. Numerous symptoms described in the case studies, including carphologia and opisthotonus, have entered the neurological vocabulary. The retrospective etiological analysis of the reports leads to the almost explicit identification of neurosyphilis and encephalitis lethargica. The therapeutic measures described by the author were, as the changeable course of the diseases shows, only of limited effectiveness despite a very differentiated application over time, both against the underlying diseases and the neurological and psychiatric complications.

Implementation and Outcome of Robotic Liver Surgery in the Netherlands: A Nationwide Analysis.

OBJECTIVE: To determine the nationwide implementation and surgical outcome of minor and major robotic liver surgery (RLS) and assess the first phase of implementation of RLS during the learning curve. BACKGROUND: RLS may be a valuable alternative to laparoscopic liver surgery. Nationwide population-based studies with data on implementation and outcome of RLS are lacking. METHODS: Multicenter retrospective cohort study including consecutive patients who underwent RLS for all indications in 9 Dutch centers (August 2014-March 2021). Data on all liver resections were obtained from the mandatory nationwide Dutch Hepato Biliary Audit (DHBA) including data from all 27 centers for liver surgery in the Netherlands. Outcomes were stratified for minor, technically major, and anatomically major RLS. Learning curve effect was assessed using cumulative sum analysis for blood loss. RESULTS: Of 9437 liver resections, 400 were RLS (4.2%) procedures including 207 minor (52.2%), 141 technically major (35.3%), and 52 anatomically major (13%). The nationwide use of RLS increased from 0.2% in 2014 to 11.9% in 2020. The proportion of RLS among all minimally invasive liver resections increased from 2% to 28%. Median blood loss was 150 mL (interquartile range 50-350 mL] and the conversion rate 6.3% (n=25). The rate of Clavien-Dindo grade ≥III complications was 7.0% (n=27), median length of hospital stay 4 days (interquartile range 2-5) and 30-day/in-hospital mortality 0.8% (n=3). The R0 resection rate was 83.2% (n=263). Cumulative sum analysis for blood loss found a learning curve of at least 33 major RLS procedures. CONCLUSIONS: The nationwide use of RLS in the Netherlands has increased rapidly with currently one-tenth of all liver resections and one-fourth of all minimally invasive liver resections being performed robotically. Although surgical outcomes of RLS in selected patient seem favorable, future prospective studies should determine its added value.

Nationwide Outcome after Pancreatoduodenectomy in Patients at very High Risk (ISGPS-D) for Postoperative Pancreatic Fistula.

OBJECTIVE: To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D. SUMMARY BACKGROUND DATA: Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking. METHODS: Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed. RESULTS: Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P<0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%). CONCLUSION: This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.

Inertial-Sensor-Based Monitoring of Sample Entropy and Peak Frequency Changes in Treadmill Walking during Recovery after Total Knee Arthroplasty.

This study aimed to investigate whether sample entropy (SEn) and peak frequency values observed in treadmill walking could provide physical therapists valuable insights into gait rehabilitation following total knee arthroplasty (TKA). It was recognized that identifying movement strategies that during rehabilitation are initially adaptive but later start to hamper full recovery is critical to meet the clinical goals and minimize the risk of contralateral TKA. Eleven TKA patients were asked to perform clinical walking tests and a treadmill walking task at four different points in time (pre-TKA, 3, 6, and 12 months post-TKA). Eleven healthy peers served as the reference group. The movements of the legs were digitized with inertial sensors and SEn and peak frequency of the recorded rotational velocity-time functions were analyzed in the sagittal plane. SEn displayed a systematic increase during recovery in TKA patients (p < 0.001). Furthermore, lower peak frequency (p = 0.01) and sample entropy (p = 0.028) were found during recovery for the TKA leg. Movement strategies that initially are adaptive, and later hamper recovery, tend to diminish after 12 months post-TKA. It is concluded that inertial-sensor-based SEn and peak frequency analyses of treadmill walking enrich the assessment of movement rehabilitation after TKA.

Therapeutic inertia during isotretinoin treatment of juvenile acne by dermatologists, paediatricians and general practitioners.

BACKGROUND: Isotretinoin is an effective treatment for severe juvenile acne, but it appears to be underused in relation to the recommendations. Therapeutic inertia is defined as a failure to initiate or intensify treatment even when warranted by the recommendations. The aim of this study was to investigate therapeutic inertia among dermatologists (D), paediatricians (P), and general practitioners (GPs) in initiating isotretinoin for moderate-to-very severe juvenile acne. METHODS: Data were collected using a questionnaire distributed to French physicians through medical societies via Internet. The questions explored the role in inertia of factors related to physicians, patients, parents, and the healthcare system, and evaluated barriers and facilitators to prescribing isotretinoin. RESULTS: In all, 768 physicians responded to the survey (528 D, 178P, and 61 GPs; mean age: 51 years; women: 78 %). Their responses revealed that 99 % of dermatologists felt comfortable prescribing isotretinoin, compared with 8 % and 15 % of paediatricians and GPs (p < 0.05); 93 % of dermatologists were aware of the current guidelines compared with 37 % of paediatricians and GPs. Under 50 % of the physicians had received training on acne in the previous 3 years, regardless of specialty. The most frequently identified factors for inertia were concerns over the psychological consequences of the treatment in adolescents, exclusive requests from parents, and patient unavailability. Paediatricians reported having insufficient knowledge of current recommendations, a lack of training, and a tendency to anticipate poor compliance. Paediatricians and GPs considered that access to first-time prescriptions and peer-to-peer exchanges would constitute facilitating factors in their use of isotretinoin. DISCUSSION: Concerns over the psychiatric consequences of isotretinoin in adolescents, the need for frequent follow-up, and lack of continuing medical education were identified as factors favouring inertia in the initiation of isotretinoin treatment in patients with moderate-to-very severe juvenile acne, particularly among paediatricians and GPs. Potential strategies to overcome these barriers include regular training, simplified recommendations in French, and access to first-time prescription for paediatricians and GPs.

Laparoscopic peritoneal lavage versus sigmoidectomy for perforated diverticulitis with purulent peritonitis: three-year follow-up of the randomised LOLA trial.

BACKGROUND: This study aimed to compare laparoscopic lavage and sigmoidectomy as treatment for perforated diverticulitis with purulent peritonitis during a 36 month follow-up of the LOLA trial. METHODS: Within the LOLA arm of the international, multicentre LADIES trial, patients with perforated diverticulitis with purulent peritonitis were randomised between laparoscopic lavage and sigmoidectomy. Outcomes were collected up to 36 months. The primary outcome of the present study was cumulative morbidity and mortality. Secondary outcomes included reoperations (including stoma reversals), stoma rates, and sigmoidectomy rates in the lavage group. RESULTS: Long-term follow-up was recorded in 77 of the 88 originally included patients, 39 were randomised to sigmoidectomy (51%) and 38 to laparoscopic lavage (49%). After 36 months, overall cumulative morbidity (sigmoidectomy 28/39 (72%) versus lavage 32/38 (84%), p = 0·272) and mortality (sigmoidectomy 7/39 (18%) versus lavage 6/38 (16%), p = 1·000) did not differ. The number of patients who underwent a reoperation was significantly lower for lavage compared to sigmoidectomy (sigmoidectomy 27/39 (69%) versus lavage 17/38 (45%), p = 0·039). After 36 months, patients alive with stoma in situ was lower in the lavage group (proportion calculated from the Kaplan-Meier life table, sigmoidectomy 17% vs lavage 11%, log-rank p = 0·0268). Eventually, 17 of 38 (45%) patients allocated to lavage underwent sigmoidectomy. CONCLUSION: Long-term outcomes showed that laparoscopic lavage was associated with less patients who underwent reoperations and lower stoma rates in patients alive after 36 months compared to sigmoidectomy. No differences were found in terms of cumulative morbidity or mortality. Patient selection should be improved to reduce risk for short-term complications after which lavage could still be a valuable treatment option.

Quantum Walks: Schur Functions Meet Symmetry Protected Topological Phases.

This paper uncovers and exploits a link between a central object in harmonic analysis, the so-called Schur functions, and the very hot topic of symmetry protected topological phases of quantum matter. This connection is found in the setting of quantum walks, i.e. quantum analogs of classical random walks. We prove that topological indices classifying symmetry protected topological phases of quantum walks are encoded by matrix Schur functions built out of the walk. This main result of the paper reduces the calculation of these topological indices to a linear algebra problem: calculating symmetry indices of finite-dimensional unitaries obtained by evaluating such matrix Schur functions at the symmetry protected points ± 1 . The Schur representation fully covers the complete set of symmetry indices for 1D quantum walks with a group of symmetries realizing any of the symmetry types of the tenfold way. The main advantage of the Schur approach is its validity in the absence of translation invariance, which allows us to go beyond standard Fourier methods, leading to the complete classification of non-translation invariant phases for typical examples.

Potential Risk and Safety Measures in Laparoscopy in COVID-19 Positive Patients.

Background. During the COVID-19 pandemic the question arises if laparoscopy, as an aerosol forming procedure, poses a potential risk for viral transmission of SARS-CoV-2 to healthcare workers. Methods. A literature search was conducted using PubMed, Embase and MEDLINE. Articles reporting information regarding COVID-19 or other relevant viruses and laparoscopy, surgical smoke, aerosols and viral transmission were included. Results. Although aerosols produced during laparoscopy do not originate from the respiratory tract, the main transmission route of SARS-CoV-2, research did show SARS-CoV-2 to be present in other body fluids. The transmission risk via this route is however considered very low. As previous research showed potential viral transmission during laparoscopy for viruses that spread through contaminated body fluids, there might be a potential risk of SARS-CoV-2 transmission during laparoscopy, albeit considered very small. Conclusion. Due to the small risk compared to widely known benefits of laparoscopy, there is no reason to replace laparoscopy by laparotomy due to COVID-19 infection. To avoid the potential small risk of viral transmission, additional safety measures are advised.

Hierarchically Structured Microsieves Produced via Float-Casting.

This article shows a new way to produce hierarchical microsieves by layering three types of float-cast microsieves, differing from each other in their pore diameters (approximately 68 µm, 7 µm, and 0.24 µm) on top of each other. The unsupported microsieves with 7 and 0.24 µm pore sizes are mechanically fragile. The complete hierarchical sieve composed of all three layers, however, can be handled manually without special precaution. This article further investigates the flow through the hierarchical sieve and filtration via experiment, theory (Hagen-Poiseuille's and Sampson-Roscoe's law), and simulation (numerically solving the Navier-Stokes equations for a predefined set of discrete volumetric elements). The experimental, theoretical, and simulated permeances of the microsieves and the hierarchical sieves are in reasonable agreement with each other and are significantly higher than the permeances of conventional filtration media. In filtration experiments, the hierarchical sieves show the expected sharp size cut-off, retaining particles of diameters exceeding the pore diameter.

The SONATA data format for efficient description of large-scale network models.

Increasing availability of comprehensive experimental datasets and of high-performance computing resources are driving rapid growth in scale, complexity, and biological realism of computational models in neuroscience. To support construction and simulation, as well as sharing of such large-scale models, a broadly applicable, flexible, and high-performance data format is necessary. To address this need, we have developed the Scalable Open Network Architecture TemplAte (SONATA) data format. It is designed for memory and computational efficiency and works across multiple platforms. The format represents neuronal circuits and simulation inputs and outputs via standardized files and provides much flexibility for adding new conventions or extensions. SONATA is used in multiple modeling and visualization tools, and we also provide reference Application Programming Interfaces and model examples to catalyze further adoption. SONATA format is free and open for the community to use and build upon with the goal of enabling efficient model building, sharing, and reproducibility.

The sense of smell is not strongly affected by ambient temperature and humidity: a prospective study in a controlled environment.

INTRODUCTION: The sense of smell is dependent on environmental conditions. In this study, we analysed the effect of temperature and humidity on the ability to smell. METHODS: Using the controlled setting of a hypobaric climate chamber 50 healthy participants (40 men, 10 women; mean age of 33 years) completed repeated testing in 4 different settings-cold/dry, cold/humid, warm/dry, warm/humid. The temperatures were 20-35 °C, respectively, and the humidity was set at 30-75%. Testing was performed using the "Sniffin' Sticks" test battery (odour threshold, discrimination and identification) in a semi-randomised order and in controlled atmospheric pressure conditions. RESULTS: The analysis showed that neither temperature nor humidity had a significant effect on olfactory test results. This indicates that olfactory functions in healthy, young subjects with an excellent sense of smell are not strongly affected by temporary changes in environmental conditions.

Cell Communication-mediated Nonself-Recognition and -Intolerance in Representative Species of the Animal Kingdom.

Why has histo-incompatibility arisen in evolution and can cause self-intolerance? Compatible/incompatible reactions following natural contacts between genetically-different (allogeneic) colonies of marine organisms have inspired the conception that self-nonself discrimination has developed to reduce invasion threats by migratory foreign germ/somatic stem cells, in extreme cases resulting in conquest of the whole body by a foreign genome. Two prominent model species for allogeneic discrimination are the marine invertebrates Hydractinia (Cnidaria) and Botryllus (Ascidiacea). In Hydractinia, self-nonself recognition is based on polymorphic surface markers encoded by two genes (alr1, alr2), with self recognition enabled by homophilic binding of identical ALR molecules. Variable expression patterns of alr alleles presumably account for the first paradigm of autoaggression in an invertebrate. In Botryllus, self-nonself recognition is controlled by a single polymorphic gene locus (BHF) with hundreds of codominantly expressed alleles. Fusion occurs when both partners share at least one BHF allele while rejection develops when no allele is shared. Molecules involved in allorecognition frequently contain immunoglobulin or Ig-like motifs, case-by-case supplemented by additional molecules enabling homophilic interaction, while the mechanisms applied to destroy allogeneic grafts or neighbors include taxon-specific tools besides common facilities of natural immunity. The review encompasses comparison with allorecognition in mammals based on MHC-polymorphism in transplantation and following feto-maternal cell trafficking.

Risk factors for reoperation in primary hand infections: a multivariate analysis.

INTRODUCTION: Severe hand infection might cause severe morbidity including stiffness, contracture and possibly amputation. The purpose of this study was to analyse the current epidemiology of adult acute hand infections in a European Hand Surgery Centre and to identify risk factors for secondary surgery. MATERIALS AND METHODS: We retrospectively analyzed a cohort of 369 consecutive patients with primary infection of the hand that were admitted to our department and required operative treatment. The following variables were recorded: demographics, medical history, cause and location of infection, laboratory values, cultured microorganisms and reoperation rate. Univariate logistical regression was used to identify variables associated with reoperation and backward selection was applied to identify the final multiple variable model. RESULTS: The mean age at the time of operation was 50.5 years (SD 16.1, range 19-91) and 65.6% of patients were male. Sharp cuts or lacerations were the most common cause (29.0%) for hand infections. 81 different species were cultivated and in 47 patients (12.7%), the cultures were positive for more than one organism. Staphylococcus aureus was the most common cultured organism (19.5%). There were relatively few cases of methicillin-resistant Staphylococcus aureus (2.2%). 80 patients (21.7%) needed more than one operation. We identified three risk factors for reoperation in a multivariate analysis: an elevated value of C-reactive protein at the time of admission, involvement of multiple sites and bacterial growth in culture. CONCLUSION: The rate of infections with MRSA in this European cohort was lower compared to reports from the USA. Thus, hand surgeons should choose their empiric antibiotic therapy depending on their patient population. The knowledge of risk factors for severe hand infections might help surgeons to identify patients at risk for additional surgery early.

Long-term Outcome of Surgery Versus Conservative Management for Recurrent and Ongoing Complaints After an Episode of Diverticulitis: 5-year Follow-up Results of a Multicenter Randomized Controlled Trial (DIRECT-Trial).

OBJECTIVE: The aim of this study was to establish whether surgical or conservative treatment leads to a higher quality of life (QoL) in patients with recurring diverticulitis and/or ongoing complaints. SUMMARY OF BACKGROUND DATA: The 6 months' results of the DIRECT trial, a randomized trial comparing elective sigmoidectomy with conservative management in patients with recurring diverticulitis (>2 episodes within 2 years) and/or ongoing complaints (>3 months) after an episode of diverticulitis, demonstrated a significantly higher QoL after elective sigmoidectomy. The aim of the present study was to evaluate QoL at 5-year follow-up. METHODS: From January 2010 to June 2014, 109 patients were randomized to either elective sigmoidectomy (N = 53) or conservative management (N = 56). In the present study, the primary outcome was QoL measured by the Gastrointestinal Quality of Life Index (GIQLI) at 5-year follow-up. Secondary outcome measures were SF-36 score, Visual Analogue Score (VAS) pain score, EuroQol-5D-3L (EQ-5D-3L) score, morbidity, mortality, perioperative complications, and long-term operative outcome. RESULTS: At 5-year follow-up, mean GIQLI score was significantly higher in the operative group [118.2 (SD 21.0)] than the conservative group [108.5 (SD 20.0)] with a mean difference of 9.7 (95% confidence interval 1.7-17.7). All secondary QoL outcome measures showed significantly better results in the operative group, with a higher SF-36 physical (P = 0.030) and mental score (P = 0.010), higher EQ5D score (P = 0.016), and a lower VAS pain score (P = 0.011). Twenty-six (46%) patients in the conservative group ultimately required surgery due to severe ongoing complaints. Of the operatively treated patients, 8 (11%) patients had anastomotic leakage and reinterventions were required in 11 (15%) patients. CONCLUSION: Consistent with the short-term results of the DIRECT trial, elective sigmoidectomy resulted in a significantly increased QoL at 5-year follow-up compared with conservative management in patients with recurring diverticulitis and/or ongoing complaints. Surgeons should counsel these patients for elective sigmoidectomy weighing superior QoL, less pain, and lower risk of new recurrences against the complication risk of surgery.

Randomized Benchmarking for Individual Quantum Gates.

Any technology requires precise benchmarking of its components, and the quantum technologies are no exception. Randomized benchmarking allows for the relatively resource economical estimation of the average gate fidelity of quantum gates from the Clifford group, assuming identical noise levels for all gates, making use of suitable sequences of randomly chosen gates. In this work, we report significant progress on randomized benchmarking, by showing that it can be applied individually on a broad class of quantum gates outside the Clifford group, even for varying noise levels per quantum gate. This is possible at little overhead of quantum resources, but at the expense of a significant classical computational cost. At the heart of our analysis is a representation-theoretic framework which we bring into contact with classical estimation techniques based on bootstrapping and matrix pencils. We demonstrate the functioning of the scheme at hand of benchmarking tensor powers of T gates. Apart from its practical relevance, we expect this insight to be relevant as it highlights the role of assumptions made on unknown noise processes when characterizing quantum gates at high precision.

Printing Reinforcing Structures onto Microsieves That Are Floating on a Water Surface.

This article describes the preparation of hierarchically structured microsieves via a suitable combination of float-casting and inkjet-printing: A mixture of hydrophobized silica particles of 600 nm ± 20 nm diameter, a suitable non-water-soluble nonvolatile acrylic monomer, a nonvolatile photoinitiator, and volatile organic solvents is applied to a water surface. This mixture spontaneously spreads on the water surface; the volatile solvents evaporate and leave behind a layer of the monomer/initiator mixture comprising a monolayer of particles, each particle protruding out of the monomer layer at the top and bottom surface. Photopolymerization of the monomer converts this mixed layer into a solid composite membrane floating on the water surface. Onto this membrane, while still floating on the water surface, a hierarchical reinforcing structure based on a photocurable ink is inkjet-printed and solidified. In contrast to the nonreinforced membrane, the reinforced membrane can easily be lifted off the water surface without suffering damage. Subsequently, the silica particles are removed, and thus, the reinforced composite membrane is converted into a reinforced microsieve of 350 nm ± 50 nm thickness bearing uniform through pores of 465 nm ± 50 nm diameter. This reinforced microsieve is mounted into a filtration unit and used to filter model dispersions: its permeance for water at low Reynolds numbers is in accordance with established theories on the permeance of microsieves and significantly above the permeance of conventional filtration media; it retains particles exceeding the pore size, while letting particles smaller than the pore size pass.

The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow.

Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channels across its processes. For a variety of physiological or pathological reasons, the intrinsic input/output function may change during a neuron's lifetime. This process results in high variability in the peak specific conductance of ion channels in individual neurons. The mechanisms responsible for this variability are not well understood, although there are clear indications from experiments and modeling that degeneracy and correlation among multiple channels may be involved. Here, we studied this issue in biophysical models of hippocampal CA1 pyramidal neurons and interneurons. Using a unified data-driven simulation workflow and starting from a set of experimental recordings and morphological reconstructions obtained from rats, we built and analyzed several ensembles of morphologically and biophysically accurate single cell models with intrinsic electrophysiological properties consistent with experimental findings. The results suggest that the set of conductances expressed in any given hippocampal neuron may be considered as belonging to two groups: one subset is responsible for the major characteristics of the firing behavior in each population and the other is responsible for a robust degeneracy. Analysis of the model neurons suggests several experimentally testable predictions related to the combination and relative proportion of the different conductances that should be expressed on the membrane of different types of neurons for them to fulfill their role in the hippocampus circuitry.