Nonrandom Order Research Articles

The Challenges Facing Global Biodiversity in Response to Climate Change

Climate change is one of the primary factors contributing to the loss of biodiversity worldwide. The purpose of this review paper was to give serious thought about the present and future impacts of climate change on biodiversity, even though we are not aware of its synergistic effects on biological populations. In order to fully understand the biota's reactions to these climatic changes, we also concentrated on how these changes impact their phenology and physiology. This review article's subjects are covered in a non-random order to make it easier for readers to understand the connections between biodiversity and climate change. We also discussed about how 1.1°C of global warming brought about by human activity has altered the Earth's climate in ways never seen before and negatively impacted human health. We covered how to safeguard our biota by implementing practical conservation strategies at the end of this review article in order to reduce the effects of climate change on it. We hope that one day, because research on climate change and biodiversity protection is interdisciplinary and spans many different scientific areas, we will be able to address all these concerns and preserve our biota from their terrible consequences.

Acute Pilates and plyometric exercise in school-based settings improve attention and mathematics performance in high school students

The aim of this study was to examine the effects of acute Pilates and plyometric exercise in a school-based setting on attention and mathematics test performance in high school students. Forty 10th-grade students (21 females and 19 males; age: [15.0 ± 0.5] years, body mass index: [21.4 ± 2.8] kg/m2) participated in this crossover and quasi-experimental study. In week 1, students were familiarized with the d2 test of attention and Pilates and plyometric exercises activities, and body composition measurements were taken. In both weeks 2 and 3, students completed the d2 test of attention and mathematics test with 20 questions following a single session of low-to-moderate-intensity exercise and a classroom-based non-exercise activity, in a non-randomized order. The exercise sessions included 30 mins of plyometric exercises for male students and Pilates exercise for female students, with intensities corresponding to 10–14 on the Borg rating of perceived exertion scale6-20. Compared to the non-exercise activity, a 30-min of Pilates and plyometric exercise resulted in significant improvements in attention score (mean difference [Δ] ​= ​54.5 score; p ​< 0.001; Cohen's effect sizes [d] ​= ​1.26) and concentration performance (Δ ​= ​20.7 score; p ​= ​0.003; d ​= ​0.51). The students scored significantly higher on the mathematics test after participating in the exercise sessions compared to the non-exercise condition (Δ% ​= ​11.7; p ​< ​0.001; d ​= ​0.76). There were no significant differences between genders (p ​> ​0.05). These findings demonstrate the effectiveness of acute light-to-moderate-intensity Pilates and plyometric exercises in school-based settings for improving attention and mathematics performance in adolescents.

Optimizing cognitive neuroscience experiments for separating event- related fMRI BOLD responses in non-randomized alternating designs.

Functional magnetic resonance imaging (fMRI) has revolutionized human brain research. But there exists a fundamental mismatch between the rapid time course of neural events and the sluggish nature of the fMRI blood oxygen level-dependent (BOLD) signal, which presents special challenges for cognitive neuroscience research. This limitation in the temporal resolution of fMRI puts constraints on the information about brain function that can be obtained with fMRI and also presents methodological challenges. Most notably, when using fMRI to measure neural events occurring closely in time, the BOLD signals may temporally overlap one another. This overlap problem may be exacerbated in complex experimental paradigms (stimuli and tasks) that are designed to manipulate and isolate specific cognitive-neural processes involved in perception, cognition, and action. Optimization strategies to deconvolve overlapping BOLD signals have proven effective in providing separate estimates of BOLD signals from temporally overlapping brain activity, but there remains reduced efficacy of such approaches in many cases. For example, when stimulus events necessarily follow a non-random order, like in trial-by-trial cued attention or working memory paradigms. Our goal is to provide guidance to improve the efficiency with which the underlying responses evoked by one event type can be detected, estimated, and distinguished from other events in designs common in cognitive neuroscience research. We pursue this goal using simulations that model the nonlinear and transient properties of fMRI signals, and which use more realistic models of noise. Our simulations manipulated: (i) Inter-Stimulus-Interval (ISI), (ii) proportion of so-called null events, and (iii) nonlinearities in the BOLD signal due to both cognitive and design parameters. We offer a theoretical framework along with a python toolbox called deconvolve to provide guidance on the optimal design parameters that will be of particular utility when using non-random, alternating event sequences in experimental designs. In addition, though, we also highlight the challenges and limitations in simultaneously optimizing both detection and estimation efficiency of BOLD signals in these common, but complex, cognitive neuroscience designs.

Methodology considerations for 'Safety and effectiveness of cannabinoids to Danish patients with treatment-refractory chronic pain' by Horsted et al.

The recently published exploratory, non-controlled, study by Horsted et al. (2023) reports on the potential safety and pain-relieving effects of cannabinoids (THC, CBD), or mixed in a non-randomized order. The authors conclude that ‘oral cannabinoid therapy in general appears to be safe and effective for relief of chronic pain in some patients, including a subset of patients with cancer-related pain (9%), not responding adequately to conventional treatment regimens or experiencing intolerable adverse events’. The author's conclusion is in direct contrast to the conclusion and recommendations from the International Associations for the Study of Pain (IASP) Cannabis Task Force. Based on a thorough evaluation of current evidence, Rice et al. (2021) concluded ‘That the available clinical evidence neither supports nor refutes claims of analgesic efficacy or safety for cannabinoids, cannabis, or cannabis-based medicines’ and suggested future studies and recommendations should follow rigid rules of conclusive randomized, placebo-controlled randomized controlled trials (RCTs) to provide evidence (Haroutounian et al., 2021). The study by Horsted et al. is a retrospective study and hence is not monitored by the Danish medical agency and executed as a good clinical practice (GCP) study although investigating the effect of a new treatment modality. Furthermore, the study was not registered at ClinicalTrials.gov as this is not normally mandatory for retrospective studies submitted to the European Journal of Pain. Many RCTs have been published demonstrating no effect of cannabinoids on clinical pain or potential underlying pain mechanisms when compared to placebo (e.g. Zubcevic et al., 2022). None of such studies and only one of the 14 IASP statement's current state-of-the-art papers are referenced in the manuscript by Horsted et al. and hence not discussed in the light of the current best evidence. The study found an average decrease in clinical pain intensity of 1.8 (baseline pain approx. 7 on a 0–10 numerical rating scale), which corresponds to an effect of approx. 25%. This is in the low end of placebo effects reported in previous high-quality pain studies and what is reported in other well-controlled placebo-controlled pain studies (McQuay et al., 1996). The expectancy and placebo effects are largely (and often exclusively) found responsible for the therapeutic effects of non-pharmacological treatments such as, e.g. cannabis. The Horsted et al. study was conducted in Denmark and here cannabis has attracted much attention in the media. The positive media promotion of cannabis products will increase the placebo effects and as the study was conducted without any control or placebo groups the effect size and the placebo responses can obviously not be separated. Most recent meta-analysis likewise concluded that ‘placebo responses contribute significantly to pain reduction in cannabinoid clinical trials’ and ‘the unusually high media attention surrounding cannabinoid trials, with positive reports irrespective of scientific results, may uphold high expectations and shape placebo responses in future’. The authors state that ‘with the relatively long follow-up it is likely that the placebo effect is of less importance’. This is not empirically validated as studies have shown long-lasting (up to 5 years) placebo effects in trials. The Horsted et al. study enrolled 826 patients, yet only 214 patients were follow-up for the last visit, 243 patients were registered as ‘lost to follow-up’ and an additional 122 patients were discontinued. In addition, among the included patients, data of interest were missing (e.g. 39 (18%) of the 214 included patients with the last visit recorded had missing values regarding pain intensity measured as numeric rating scale). Only 25.9% (214/826) of the included eligible patients were included in the analysis. All these excluded patients are likely to not benefit from the study drug (no effect or severe side effects), which is not addressed in details. Thus, the excluded patients (constituting +40% of the original sample) are a likely source of a major selection bias, compromising the study's validity and conclusions. The authors do refer to the supplementary material for a description of the excluded patients, but this material is not presented in a way that allows for further analyses. The exploratory nature of this non-placebo controlled cannabis study does not provide new evidence for the use of cannabinoids for the treatment of pain. The pain alleviation reported is at its best similar to placebo responses reported in multiple randomized pain cannabis trials. The concerningly high number of patients excluded from the analysis further compromises the integrity and validity of the study. Center for Neuroplasticity and Pain (CNAP) is supported by the Danish National Research Foundation (DNRF121). The Center for Mathematical Modeling of Knee Osteoarthritis (MathKOA) is funded by the Novo Nordisk Foundation (NNF21OC0065373). The authors declare no conflict of interest.

Effects of micropipette handle diameter and inclusion of finger rest on basilar thumb joint contact mechanics.

Micropipette users commonly experience problems in the hand and upper limbs. Mechanical factors are thought to contribute to osteoarthritis (OA) initiation and progression in the basilar thumb joint. Finite element analysis can be used to examine the effects of micropipette design on contact mechanics measures within the basilar thumb joint. This pilot study examined the effect of micropipette handle diameter (12mm, 25mm, and 40mm) and the presence of a finger rest on contact area, contact force, and peak contact pressure in the basilar thumb joint. All contact mechanics measures decreased with increasing handle diameter with significant differences between the 12mm diameter and the 40mm diameter handles (contact area down about 30 mm2, contact force down about 15N, and peak pressure down about 1MPa). Decreasing contact mechanics measures with increasing diameter matched our expectations that contact measures would decrease with a more open grip. Contact mechanics measures were higher (p < 0.05) with a finger rest for contact area and force. We expected peak contact pressure and contact area to decrease with the presence of a finger rest. The unexpected outcome may have been due to non-randomized testing order and fatigue during testing.

Control theory illustrates the energy efficiency in the dynamic reconfiguration of functional connectivity

The brain’s functional connectivity fluctuates over time instead of remaining steady in a stationary mode even during the resting state. This fluctuation establishes the dynamical functional connectivity that transitions in a non-random order between multiple modes. Yet it remains unexplored how the transition facilitates the entire brain network as a dynamical system and what utility this mechanism for dynamic reconfiguration can bring over the widely used graph theoretical measurements. To address these questions, we propose to conduct an energetic analysis of functional brain networks using resting-state fMRI and behavioral measurements from the Human Connectome Project. Through comparing the state transition energy under distinct adjacent matrices, we justify that dynamic functional connectivity leads to 60% less energy cost to support the resting state dynamics than static connectivity when driving the transition through default mode network. Moreover, we demonstrate that combining graph theoretical measurements and our energy-based control measurements as the feature vector can provide complementary prediction power for the behavioral scores (Combination vs. Control: t = 9.41, p = 1.64e−13; Combination vs. Graph: t = 4.92, p = 3.81e−6). Our approach integrates statistical inference and dynamical system inspection towards understanding brain networks.

Effect of controlled sequential elevation timing of the head and thorax during cardiopulmonary resuscitation on cerebral perfusion pressures in a porcine model of cardiac arrest

AimControlled sequential elevation of the head and thorax (CSE) during active compression–decompression (ACD) CPR with an impedance threshold device (ITD) augments cerebral (CerPP) and coronary (CorPP) perfusion pressures. The optimal CSE is unknown. MethodsAfter 8 minutes of untreated VF, 40 kg anesthetized female pigs were positioned on a customized head and thorax elevation device (CED). After 2 min of automated ACD + ITD-16 CPR to ‘prime the system’, 12 pigs were randomized to CSE to the highest CED position over 4-min or 10-min. The primary outcome was CerPP after 7 minutes of CPR. Secondarily, 24-sec (without a priming step) and 2-min CSE times were similarly tested (n = 6 group) in a non-randomized order. Values expressed as mean ± SD. ResultsAfter 7 min of CPR, CerPPs were significantly higher in the 4-min vs 10-min CSE groups (53 ± 14.4 vs 38.5 ± 3.6 mmHg respectively, p = 0.03) whereas CorPP trended higher. The 4-min CSE group achieved 50% of baseline (50% BL) CerPP faster than the 10-min group (2.5 ± 1.2 vs 6 ± 3.1 minutes, p = 0.03). CerPP values in the 2-min and 4-min CSE groups were significantly higher than in the 24-sec group. With CSE, CerPPs and CorPPs increased over time in all groups. ConclusionsBy optimizing controlled sequential elevation timing, CerPP values achieved 50% of baseline within less than 2.5 minutes and >80% of baseline after 7 minutes of CPR. This novel CPR approach rapidly restored CerPPs to near normal values non-invasively and without vasopressors.

Trust in context: National heuristics and survey context effects on political trust in the European Union

Trust in the European Union is strongly related to trust in national political institutions through extrapolation, i.e. cues from national politics. Most evidence for this mechanism, however, is based on surveys using question blocks that present several institutions at once in non-randomized order. We conducted six split-ballot survey experiments in five European countries, asking about trust in national and European Union institutions (a) separately or in the same question block and (b) in different question orders. Our findings demonstrate survey context effects: asking about two institutions within the same question block increases the correlation of reported levels of trust in these institutions. Furthermore, our findings indicate that national primes decrease reported trust in the European Union, providing novel micro-level evidence for extrapolation and cue-taking from national politics in the formation of public opinion about the European Union.

Cellular Cognition: Sequential Logic in a Giant Protist.

Quantitative analysis of the giant ciliate Stentor roeselii shows that a single cell can make decisions, based on the ability to switch between several different behaviors in a non-random order.

Burrow usage patterns and decision-making in meerkat groups

Abstract Choosing suitable sleeping sites is a common challenge faced by animals across a range of taxa, with important implications for the space usage patterns of individuals, groups, and ultimately populations. A range of factors may affect these decisions, including access to resources nearby, shelter from the elements, safety from predators, territorial defense, and protection of offspring. We investigated the factors driving patterns of sleeping site use in wild Kalahari meerkats (Suricata suricatta), a cooperatively breeding, territorial mongoose species that forages on scattered resources and makes use of multiple sleeping sites (burrows). We found that meerkat groups used some burrows much more often than others. In particular, large burrows near the center of the territory were used more often than small and peripheral burrows, and groups became even more biased toward central burrows when rearing pups. Meerkats also used their sleeping burrows in a nonrandom order. When they changed sleeping burrows, they moved disproportionately to nearby burrows but did not always select the closest burrow. Burrow decisions also reflected responses to short-term conditions: rates of switching burrows increased after encounters with predators and when resources were depleted, whereas group splits were associated with a reduced probability of switching. The group’s dominant female appeared to have disproportionate influence over burrow decisions, as groups were more likely to switch burrows when her foraging success was low. Our results link behavioral and movement ecology to show that a multitude of environmental and social factors shape daily group decisions of where to spend the night.

Acid hydrolysis of glycosidic bonds in oat β‐glucan and development of a structured kinetic model

Homogeneous acid‐catalyzed hydrolysis of oat β‐glucan, which contains β‐(1,4) and β‐(1,3) glycosidic bonds in a nonrandom order, was studied at 353 K using HCl and H2SO4. A new structured kinetic model was developed that takes into account the difference in the reactivity of β‐(1,4) and β‐(1,3) glycosidic bonds as well as their positions in the polysaccharide chain. To minimize the correlation of adjustable parameters in the new model, the reactivities of these bonds were studied independently (T = 313…363 K; cH+ = 0.1…2 mol/L) using cellobiose and laminaribiose. The difference in kinetic parameters (e.g., T = 338 K: kβ‐(1,4) = 0.693 × 10−3 L/mol/min, kβ‐(1,3) = 1.027 × 10−3 L/mol/min) was found to be statistically significant (P &lt; 0.0001), which emphasizes the need for the structured model for oat β‐glucan hydrolysis. The simulation of β‐glucan hydrolysis with the new model was in good agreement with the experimental data and shows improvement over existing nonstructured models. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2570–2580, 2018

Dissociable effects of practice variability on learning motor and timing skills.

Motor skill acquisition inherently depends on the way one practices the motor task. The amount of motor task variability during practice has been shown to foster transfer of the learned skill to other similar motor tasks. In addition, variability in a learning schedule, in which a task and its variations are interweaved during practice, has been shown to help the transfer of learning in motor skill acquisition. However, there is little evidence on how motor task variations and variability schedules during practice act on the acquisition of complex motor skills such as music performance, in which a performer learns both the right movements (motor skill) and the right time to perform them (timing skill). This study investigated the impact of rate (tempo) variability and the schedule of tempo change during practice on timing and motor skill acquisition. Complete novices, with no musical training, practiced a simple musical sequence on a piano keyboard at different rates. Each novice was assigned to one of four learning conditions designed to manipulate the amount of tempo variability across trials (large or small tempo set) and the schedule of tempo change (randomized or non-randomized order) during practice. At test, the novices performed the same musical sequence at a familiar tempo and at novel tempi (testing tempo transfer), as well as two novel (but related) sequences at a familiar tempo (testing spatial transfer). We found that practice conditions had little effect on learning and transfer performance of timing skill. Interestingly, practice conditions influenced motor skill learning (reduction of movement variability): lower temporal variability during practice facilitated transfer to new tempi and new sequences; non-randomized learning schedule improved transfer to new tempi and new sequences. Tempo (rate) and the sequence difficulty (spatial manipulation) affected performance variability in both timing and movement. These findings suggest that there is a dissociable effect of practice variability on learning complex skills that involve both motor and timing constraints.

A validated translation of a survey for measuring incontinence knowledge in Chinese-speaking American immigrants.

Urinary incontinence is common amongst Chinese immigrants. These women are a rapidly growing population in the USA who require unique assessment tools due to language barriers. Presently, there are no Chinese language surveys to assess knowledge of urinary incontinence. Our goal was to translate and validate a urinary incontinence knowledge survey from English into Chinese. The English language Urinary Incontinence Quiz (UIQ) developed and validated by Branch et al. for the Educational Demonstration of Urinary Continence Assessment and Treatment for the Elderly program assesses general knowledge of urinary incontinence as a disease entity. We translated it into Chinese using the forward translation/back translation technique. The Chinese and English versions were then administered to bilingual volunteers in a nonrandomized order during a single encounter. Their responses were analyzed using Cohen's kappa coefficient to establish the validity of the translated knowledge survey. Minimal reconciliation was needed in construction of the Chinese survey. Minor English grammatical corrections were made to the back-translated English survey. One question testing two knowledge concepts was separated into two questions to allow clear testing of both concepts individually. Twenty-one bilingual participants performed the validity testing. Over 50% (8 out of 15) of the questions showed nearly perfect agreement with a kappa coefficient >0.80, 5 out of the 15 questions showed substantial agreement with kappa coefficients between 0.61 and 0.8 and two questions showed moderate agreement with kappa coefficients between 0.4 and 0.6. We validated a translation of the UIQ for assessment of urinary incontinence knowledge in Chinese-speaking immigrants to the USA.

Feasibility of Hypoxic Challenge Testing in Youth with Congenital Heart and Lung Disease

At altitude the partial pressure of oxygen declines and causes hypobaric hypoxia. This may leads to hypoxemia in patients with congenital heart or lung disease, because of their limited compensatory cardiorespiratory capacity. For this reason a hypoxic challenge test (HCT), usually performed in resting conditions, is recommended. However, also the possible effects of changing body position and physical activity at altitude can be relevant, because it may lead to further desaturation. PURPOSE: The primary aim of this study was to investigate the effects of integrating changing body positions and physical activity in a HCT among youth with severe congenital heart or lung disease. METHODS: SpO2 and heart rate were monitored in 12 pediatric patients with congenital heart or lung disease undergoing a modified HCT, breathing room air (21% oxygen) while sitting and breathing 15% oxygen in nitrogen while seated, lying supine, standing, walking 3 km/hr and walking 5 km/hr in a non-randomized order. Data were analyzed using a Friedman test. RESULTS: All patients, except one, passed successfully through the entire HCT protocol. Three patients reported symptoms, possible related to altitude hypoxia. Median pulse oximeter saturation breathing 15% oxygen decreased from 99% to 95% in all body positions (seated, supine, standing) compared with room air (p<0.0001). There were no significant differences in pulse oximeter saturations between the different body positions. During mild exercise breathing 15% oxygen the pulse oximeter saturations decreased significantly from 99% to 94% compared to breathing 21% oxygen at rest (p<0.001). No significant differences between mild exercise breathing 15% oxygen and breathing 15% oxygen at rest was found. Several patients had SpO2 values below 90% at some point during the HCT. The pulse oximeter attached to the forehead registered significantly higher saturations (median and minimum values) than the pulse oximeter attached to the index finger (medians: 92% vs 94/95% respectively; p≤0.05). CONCLUSION: Simulated hypoxia of 2500 meter induced a small but significant decrease in SpO2% in pediatric patients with congenital heart or lung disease. These values were not further lowered during walking 3 and 5 km/hr. Supported by a grant of the Prof Dr Jongbloed Foundation.

Balancing the critical period of spiking neurons with attractor-less STDP

Attractor-based (multiplicative) STDP has been called a biologically more realistic form of spike timing dependent plasticity than attractor-less (additive) variants [1-4], as it produces unimodal distributions of synaptic weights [5,6] when given poisson-distributed random input spike trains [1,2,4,7-9]. While unimodal weight distributions have been observed as an outcome in some in vitro experiments [5], the actual biochemical process that changes synaptic connection strengths has yet to be fully understood. Unfortunately, attractor-based STDP has been repeatedly shown to be computationally less powerful than attractor-less STDP [9] and successful implementations of attractor-based STDP used attractors that were either very weak [8] or very close to some minimum weight [2,3], causing a more additive-like [2,8] behaviour of the plasticity rule. We therefore examined possible biological interpretations of attractor-less STDP rules while keeping in mind that any STDP rule is just an abstraction from the hidden biophysical reality. We show how unimodal weight distributions can reliably result from attractor-less STDP when negative synaptic drift is combined with activity-independent synaptic growth. A bimodal distribution is then only formed when non-random (polychromous [10]) poisson-distributed inputs are presented to a neuron [11]. In practice, this produces a plasticity rule that keeps the postsynaptic neuron unselective and responsive to a broad range of inputs while receiving only random spikes, but quickly allows the neuron's receptive field to become highly selective as soon as some inputs start repeating a non-random ordering of spikes. This stabilization procedure preserves STDP's sensitivity to temporally shifted correlations in input spike data, which in turn gives us several beneficial features for biologically more realistic and computationally more powerful [12] implementations of plasticity in spiking neural networks.

Individual calling behaviour and movements of North Atlantic minke whales (Balaenoptera acutorostrata)

Information on individual calling behaviour and source levels are important for understanding acoustically mediated social interactions of marine mammals, for which visual observations are difficult to obtain. Our study, conducted in the Stellwagen Bank National Marine Sanctuary (SBNMS), located in the Gulf of Maine, USA, used passive acoustic arrays to track North Atlantic minke whales and assess the sound production behaviour of individuals. A total of 18 minke whales were acoustically tracked in this study. Individual calling rates were variable, with a median intercall interval (ICI) of 60.3 s. Average source levels (SLrms) for minke whales pulse trains ranged between 164 and 168 dB re 1 μPa, resulting in a minimum detection range of 0.4–10.2 km for these calls in this urban, coastal environment. All tracked animals were actively swimming at a speed of 5.0 ± 1.2 km/h, which matches swimming speeds of migrating minke whales from other areas and confirms SBNMS as part of the migration route of this species in the Western North Atlantic. Tracked minke whales produced 7 discrete call types belonging to 3 main categories, yet no individual produced all call types. Instead, minke whales produced 2 multisyllabic call sequences (A and B) by combining 3–4 different call types in a non-random order. While 7 of the tracked individuals produced calling pattern A, 10 whales used calling pattern B, and only 1 animal combined call types differently. Animals producing different call sequences were in acoustic range of one another on several occasions, suggesting they may use these sequences for mediating social interactions. The fact that the same calling patterns were shared by several individuals suggests that these patterns may contain information related to sex, age or behavioural context.

Neurally adjusted ventilatory assist improves patient-ventilator synchrony during prophylactic helmet ventilation following aortic surgery

IntroductionDuring postoperative non-invasive ventilation (NIV), following abdominal aortic surgery, leaks and diaphragmatic dysfunction jeopardize patient-ventilator interaction. We hypothesized that neurally adjusted ventilatory assist (NAVA) would be efficient to perform NIV with a helmet, and would reduce triggering and cycling-off delays as well as major patient-ventilator asynchronies compared to pressure support ventilation (PSV). MethodsNine postoperative patients receiving NIV with a helmet following abdominal aortic surgery were included. After optimization of ventilator settings, 15-min recording were performed with PSV (H-PSV) and NAVA mode (H-NAVA) in a non-random order. Breathing pattern descriptors, diaphragm electrical activity, leak volume, inspiratory trigger delay and cycling-off delay and the five main asynchronies were quantified. Asynchrony index (AI) and asynchrony index influenced by leaks (AILEAKS) were computed. Data is displayed as a median [25–75 interquartiles]. ResultsTrigger delays were lower with H-NAVA than with H-PSV (respectively 143 [54; 244] and 804 [406; 906] ms, P=0.02), as were the cycling-off delays (respectively −702 [−780; −534] and 437 [176; 695] ms, P=0.004). Although it had no effect on AI, H-NAVA decreased AILEAKS (5 [2; 10] vs. 16 [8; 28] %, P=0.004), mostly due to a drastic reduction of the prevalence of ineffective triggering (0.6 [0.1; 1.15] vs. 1.7 [1.1; 4.5] min−1, P=0.009). Tidal volumes and ventilatory command remained unchanged, but peak pressure level was lower with the H-NAVA than with H-PSV (16 [15–19] vs. 22 [20; 23] cmH2O, P=0.004). ConclusionNAVA mode is sensitive enough to ensure ventilation despite postoperative diaphragmatic dysfunction. In combination with a helmet, NAVA improves patient-ventilator interaction during prophylactic postoperative NIV. The impact on patient outcome remains yet to be determined.

Schooling Fish Under Attack Are Not All Equal: Some Lead, Others Follow

Animal groups such as fish schools, bird flocks and insect swarms appear to move so synchronously that they have long been considered egalitarian, leaderless units. In schooling fish, video observations of their spatial-temporal organization have, however, shown that anti-predator manoeuvres are not perfectly synchronous and that individuals have spatial preferences within the school. Nonetheless, when facing life-or-death situations, it is not known whether schooling fish react to a threat following a random or a hierarchically-based order. Using high-speed video analysis, here we show that schooling fish (Golden grey mullet, Liza aurata) evade a threat in a non-random order, therefore individuals that are first or last to react tend to do so repeatedly over sequential stimulations. Furthermore, startle order is strongly correlated with individual positional preferences. Because school members are known to follow individuals that initiate a manoeuvre, early responders are likely to exert the strongest influence on the escape strategy of the whole school. Our results present new evidence of the intrinsic heterogeneity among school members and provide new rules governing the collective motion of gregarious animals under predator attack.

Evolution of Antibiotic Resistance through a Multi-Peaked Adaptive Landscape

Antibiotic resistance is an evolving threat to public health. Understanding the evolution of antibiotic resistance at the genetic level is critical to develop novel strategies to diagnose and treat antibiotic resistant infections. We recently developed an automated microbial selection device, the “morbidostat”, which is used to study the evolution of antibiotic resistance in dynamically sustained drug selection. The morbidostat adjusts drug concentrations to maintain nearly constant inhibition of bacterial growth even as evolving bacterial populations acquire higher resistance. using the morbidostat and next generation sequencing, we identified striking features in the evolution of trimethoprim resistance in five E. coli populations evolving in parallel. We found that resistance was acquired in a stepwise manner, through multiple mutations almost exclusively restricted to the gene encoding trimethoprim's target, dihydrofolate reductase (DHFR). Multiple distinct genotypes produced very similar trimethoprim resistant phenotypes, with each highly evolved strain each containing four mutations from a set of six possibilities, that were acquired in a non-random order. Never were more than four mutations acquired, despite sustained selection for further increases in drug resistance, indicating that these genotypes were local adaptive peaks.In order to understand how the adaptive landscape of drug resistance contained multiple peaks, all combinatorial sets of adaptive mutations in the DHFR gene (96 strains) were constructed and characterized. These measurements showed that resistance evolves through an almost maximally rugged adaptive landscape with direct and indirect trajectories leading to distinct peaks. The ruggedness was not explained by pairwise incompatibilities between mutations, instead indicating ‘high-order' genetic interactions between mutations. These high-order interactions were responsible for the existence of multiple adaptive peaks. One mutation was seen to have the power to control the adaptive landscape: its presence or absence largely defined the ruggedness or smoothness of the adaptive landscape.

Positioning of Chromosomes in Human Spermatozoa Is Determined by Ordered Centromere Arrangement

The intranuclear positioning of chromosomes (CHRs) is a well-documented fact; however, mechanisms directing such ordering remain unclear. Unlike somatic cells, human spermatozoa contain distinct spatial markers and have asymmetric nuclei which make them a unique model for localizing CHR territories and matching peri-centromere domains. In this study, we established statistically preferential longitudinal and lateral positioning for eight CHRs. Both parameters demonstrated a correlation with the CHR gene densities but not with their sizes. Intranuclear non-random positioning of the CHRs was found to be driven by a specific linear order of centromeres physically interconnected in continuous arrays. In diploid spermatozoa, linear order of peri-centromeres was identical in two genome sets and essentially matched the arrangement established for haploid cells. We propose that the non-random longitudinal order of CHRs in human spermatozoa is generated during meiotic stages of spermatogenesis. The specific arrangement of sperm CHRs may serve as an epigenetic basis for differential transcription/replication and direct spatial CHR organization during early embryogenesis.