Hospital re-admission after critical care survival: a systematic review and meta-analysis.

Survivors of critical illness frequently require increased healthcare resources after hospital discharge. We undertook a systematic review and meta-analysis to assess hospital re-admission rates following critical care admission and to explore potential re-admission risk factors. We searched the MEDLINE, Embase and CINAHL databases on 05 March 2020. Our search strategy incorporated controlled vocabulary and text words for hospital re-admission and critical illness, limited to the English language. Two reviewers independently applied eligibility criteria and assessed quality using the Newcastle Ottawa Score checklist and extracted data. The primary outcome was acute hospital re-admission in the year after critical care discharge. Of the 8851 studies screened, 87 met inclusion criteria and 41 were used within the meta-analysis. The analysis incorporated data from 3,897,597 patients and 741,664 re-admission episodes. Pooled estimates for hospital re-admission after critical illness were 16.9% (95%CI: 13.3-21.2%) at 30 days; 31.0% (95%CI: 24.3-38.6%) at 90 days; 29.6% (95%CI: 24.5-35.2%) at six months; and 53.3% (95%CI: 44.4-62.0%) at 12 months. Significant heterogeneity was observed across included studies. Three risk factors were associated with excess acute care rehospitalisation one year after discharge: the presence of comorbidities; events during initial hospitalisation (e.g. the presence of delirium and duration of mechanical ventilation); and subsequent infection after hospital discharge. Hospital re-admission is common in survivors of critical illness. Careful attention to the management of pre-existing comorbidities during transitions of care may help reduce healthcare utilisation after critical care discharge. Future research should determine if targeted interventions for at-risk critical care survivors can reduce the risk of subsequent rehospitalisation.

Corrigendum to "Which factor is more important for the welfare of broiler chickens: Intensity or duration of episodic heat stress?" [J. Therm. Biol. 99 (2021) 102981].

Due to the effects of global warming, there is a predicted increase in the frequency, intensity and duration of heat waves in the future. Little is known of how this could affect the welfare of broiler chickens. Sixty-four broiler chickens were subjected to either high heat stress (HHS; 32oC, 70% RH for 3 h), moderate heat stress (MHS; 30oC, 70% RH for 6 h), or normal conditions (NC: 20oC, 50% RH for 6 h) for two consecutive days. Half the birds had been subjected to anaesthesia and fitted with a body temperature-ID chip placed in the breast muscle. Core body temperature (CBT) was taken during pre-heat stress (PrHS), at the end of 3 h (3HS) and 6 h (6HS) of heat stress using a pocket reader and used to estimate change in CBT (ΔCBT). Surface body temperatures (SBTs) from under the wing (WT), feet (FT), cloaca (CLT) and comb (CT) were also measured, along with blood parameters, feed intake, daily weight gain and mortality. Data were analysed using General Linear Model and simple linear regression. At 3HS, CBT/ΔCBT and all SBTs showed this trend: HHS > MHS > NC (P<0.001). Blood pH, pCO2, iCa, HCO3- and TCO2 showed the same trend: HHS, MHS > NC (P<0.05). Comparing HHS for 3 h with MHS and NC for 6 h showed that CBT/ΔCBT, WT and CLT in HHS, MHS > control (P<0.001) while FT and CT showed a different trend (HHS > MHS > NC, P<0.001). Exposure of broiler chickens to 3 hours of HHS had dramatic effects on core and surface body temperatures. The effects of MHS were initially more modest yet, after a further 3 hours exposure, resulted in an increase in CBT which was close to that which HHS birds experienced after just 3 hours. This illustrates that duration of exposure to heat stress can have a critical effect, achieving similar life-threatening changes in body temperature that were observed under higher levels of heat stress but for half the time.

Which factor is more important: Intensity or duration of episodic heat stress on broiler chickens?

With the current global warming, there is a predicted increase in frequency, intensity and duration of heat waves in future. Little is known of how this could affect the welfare of broiler chickens. Sixty-four broiler chickens were subjected to either high heat stress (HHS; 32 °C, 70% RH for 3 h), moderate heat stress (MHS; 30 °C, 70% RH for 6 h), or normal conditions (NC: 20 °C, 50% RH for 6 h) for two consecutive days. On both days, the temperature-ID chips on all chipped birds were scanned during pre-heat stress (PrHS), end of 3 h (3HS) and 6 h (6HS) of heat stress using a pocket reader. Half of the chip birds' CBT was measured at the end of each hour of heat stress (HS: 1st -3rd hour). Surface body temperatures (SBTs) from under the wing (WT), feet (FT), cloaca (CLT) and comb (CT) were measured. Blood samples, feed intake, daily weight gain and mortality was also monitored. Data was analysed using General Linear Model and simple linear regression. At 3HS, CBT/ΔCBT and all SBTs showed this trend: HHS>MHS>NC (P<0.001). The regression equations to predict ΔCBT in HHS and MHS are ΔCBT = 0.917 + 0.663 h, P<0.05 and ΔCBT = 0.371 + 0.338 h, P<0.05 respectively. Blood pH, pCO2, iCa, HCO3- and TCO2 showed same trend: HHS, MHS > NC (P<0.05). Comparing HHS for 3 h with MHS and NC for 6 h shows that CBT/ΔCBT, WT and CLT in HHS, MHS>control (P<0.001) while FT and CT showed a different trend (HHS > MHS > NC, P<0.001). pCO2, feed intake and daily weight gain showed same trend (HHS, MHS > control). Temperature-ID chip (a less invasive technique) gave CBT/ΔCBT values that corresponded with the degree of heat stress experienced by the birds. Broilers were more tolerant to MHS than HHS after 3 h but MHS for 6 h and HHS for 3 h had similar impact.

Predictive Modeling of Tacrolimus Dose Requirement Based on High-Throughput Genetic Screening.

Any biochemical reaction underlying drug metabolism depends on individual gene-drug interactions and on groups of genes interacting together. Based on a high-throughput genetic approach, we sought to identify a set of covariant single-nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C0 ) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable-selection strategy to reinforce the stability of the variable-selection process and multivariate modeling. Our predictive models explained up to 70% of total variability in Tac C0 per dose with a maximum of 44 gene variants (p-value <0.001 with a permutation test). These models included molecular networks of drug metabolism with oxidoreductase activities and the multidrug-resistant ABCC8 transporter, which was found in the most stringent model. Finally, we identified an intronic variant of the gene encoding SLC28A3, a drug transporter, as a key gene involved in Tac metabolism, and we confirmed it in an independent validation cohort.

Do horses with poor welfare show 'pessimistic' cognitive biases?

This field study tested the hypothesis that domestic horses living under putatively challenging-to-welfare conditions (for example involving social, spatial, feeding constraints) would present signs of poor welfare and co-occurring pessimistic judgement biases. Our subjects were 34 horses who had been housed for over 3 years in either restricted riding school situations (e.g. kept in single boxes, with limited roughage, ridden by inexperienced riders; N = 25) or under more naturalistic conditions (e.g. access to free-range, kept in stable social groups, leisure riding; N = 9). The horses' welfare was assessed by recording health-related, behavioural and postural indicators. Additionally, after learning a location task to discriminate a bucket containing either edible food ('positive' location) or unpalatable food ('negative' location), the horses were presented with a bucket located near the positive position, near the negative position and halfway between the positive and negative positions to assess their judgement biases. The riding school horses displayed the highest levels of behavioural and health-related problems and a pessimistic judgment bias, whereas the horses living under more naturalistic conditions displayed indications of good welfare and an optimistic bias. Moreover, pessimistic bias data strongly correlated with poor welfare data. This suggests that a lowered mood impacts a non-human species' perception of its environment and highlights cognitive biases as an appropriate tool to assess the impact of chronic living conditions on horse welfare.

Using body temperature, food and water consumption as biomarkers of disease progression in mice with Eµ-myc lymphoma.

BACKGROUND: Non-invasive biomarkers of disease progression in mice with cancer are lacking making it challenging to implement appropriate humane end points. We investigated whether body temperature, food and water consumption could be used to predict tumour burden. METHODS: Thirty-six male, wild-type C57Bl/6 mice were implanted with subcutaneous RFID temperature sensors and inoculated with Eµ-myc tumours that infiltrate lymphoid tissue. RESULTS: Decrease in body temperature over the course of the study positively predicted post-mortem lymph node tumour burden (R(2)=0.68, F(1,22)=44.8, P<0.001). At experimental and humane end points, all mice that had a mean decrease in body temperature of 0.7 °C or greater had lymph nodes heavier than 0.5 g (100% sensitivity), whereas a mean decrease in body temperature <0.7 °C always predicted lymph nodes lighter than 0.5 g (100% specificity). The mean decrease in food consumption in each cage also predicted mean post-mortem lymph node tumour burden at 3 weeks (R(2)=0.89, F(1,3)=23.2, P=0.017). CONCLUSION: Temperature, food and water consumption were useful biomarkers of disease progression in mice with lymphoma and could potentially be used more widely to monitor mice with other forms of cancer.

Constrained Domain Adaptation for Image Segmentation.

Domain Adaption tasks have recently attracted substantial attention in computer vision as they improve the transferability of deep network models from a source to a target domain with different characteristics. A large body of state-of-the-art domain-adaptation methods was developed for image classification purposes, which may be inadequate for segmentation tasks. We propose to adapt segmentation networks with a constrained formulation, which embeds domain-invariant prior knowledge about the segmentation regions. Such knowledge may take the form of anatomical information, for instance, structure size or shape, which can be known a priori or learned from the source samples via an auxiliary task. Our general formulation imposes inequality constraints on the network predictions of unlabeled or weakly labeled target samples, thereby matching implicitly the prediction statistics of the target and source domains, with permitted uncertainty of prior knowledge. Furthermore, our inequality constraints easily integrate weak annotations of the target data, such as image-level tags. We address the ensuing constrained optimization problem with differentiable penalties, fully suited for conventional stochastic gradient descent approaches. Unlike common two-step adversarial training, our formulation is based on a single segmentation network, which simplifies adaptation, while improving training quality. Comparison with state-of-the-art adaptation methods reveals considerably better performance of our model on two challenging tasks. Particularly, it consistently yields a performance gain of 1-4% Dice across architectures and datasets. Our results also show robustness to imprecision in the prior knowledge. The versatility of our novel approach can be readily used in various segmentation problems, with code available publicly.

A natural view of microbial biodiversity within hot spring cyanobacterial mat communities.

This review summarizes a decade of research in which we have used molecular methods, in conjunction with more traditional approaches, to study hot spring cyanobacterial mats as models for understanding principles of microbial community ecology. Molecular methods reveal that the composition of these communities is grossly oversimplified by microscopic and cultivation methods. For example, none of 31 unique 16S rRNA sequences detected in the Octopus Spring mat, Yellowstone National Park, matches that of any prokaryote previously cultivated from geothermal systems; 11 are contributed by genetically diverse cyanobacteria, even though a single cyanobacterial species was suspected based on morphologic and culture analysis. By studying the basis for the incongruity between culture and molecular samplings of community composition, we are beginning to cultivate isolates whose 16S rRNA sequences are readily detected. By placing the genetic diversity detected in context with the well-defined natural environmental gradients typical of hot spring mat systems, the relationship between gene and species diversity is clarified and ecological patterns of species occurrence emerge. By combining these ecological patterns with the evolutionary patterns inherently revealed by phylogenetic analysis of gene sequence data, we find that it may be possible to understand microbial biodiversity within these systems by using principles similar to those developed by evolutionary ecologists to understand biodiversity of larger species. We hope that such an approach guides microbial ecologists to a more realistic and predictive understanding of microbial species occurrence and responsiveness in both natural and disturbed habitats.

16S rRNA sequences reveal uncultured inhabitants of a well-studied thermal community.

Molecular methods are beginning to reveal inhabitants of natural microbial communities which have never before been cultured. Our approach involves selective cloning of naturally occurring 16S rRNA sequences as cDNA, and comparison of these sequences to a database which includes 16S rRNA sequences of isolated community members. We provide here an overview of the method and its potential for community analysis. A 16S rRNA sequence retrieved from the well-studied hot spring cyanobacterial mat in Octopus Spring (Yellowstone National Park) is shown as an example of one contributed by an uncultured member of the community.

Risk-sensitivity: crossroads for theories of decision-making.

Most actions result in one of a set of possible outcomes. To understand how this uncertainty, or risk, affects animals' decision-making some researchers take a normative approach, asking how an animal should respond to risk if it is maximizing its fitness. Others focus on predicting responses to risk by generalizing from regularities in behavioural data, without reference to cognitive processes. Yet others infer cognitive processes from observed behaviour and ask what actions are predicted when these processes interact with risk. The normative approach (Risk-sensitivity Theory; RST) is unique in predicting a shift in a subject's response to risk as a function of its resource budget, but the predictions of this theory are not yet widely confirmed. In fact, evidence suggests a strong bias towards risk-proneness when delay to reward is risky and risk-aversion when amount of reward is risky, a pattern not readily explained by RST. Extensions of learning theory and of Scalar Expectancy Theory provide process-based explanations for these findings but do not handle preference shifts or provide evolutionary justification for the processes assumed. In this review we defend the view that risk-sensitivity must be studied with theoretical plurality.

A novel fluorescent marker for assembled mitochondria ATP synthase of yeast. OSCP subunit fused to green fluorescent protein is assembled into the complex in vivo.

We have shown that OSCP, a subunit of yeast mitochondrial ATP synthase, can be incorporated into the intact enzyme as a fusion protein representing OSCP fused at its C-terminus to the green fluorescent protein (GFP) of Aequorea victoria. The relevant fusion OSCP-GFP-h6 additionally contains a hexahistidine tag at the C-terminus. Expression of OSCP-GFP-h6 in yeast cells lacking endogenous OSCP led to the efficient restoration of growth of cells on the non-fermentable substrate, ethanol. Confocal laser scanning microscopy revealed fluorescence due to GFP in mitochondria of cells expressing OSCP-GFP-h6. Use of immobilised metal ion affinity chromatography enabled the recovery of assembled ATP synthase complexes which contained OSCP-GFP-h6 identified by its mobility on SDS-PAGE and immunoreactivity to anti-OSCP and anti-GFP antibodies. The successful isolation of the assembled multisubunit ATP synthase containing GFP fused to one of the essential subunits of the complex widely expands the potential applications of GFP. In principle, these include the spatial and temporal monitoring of ATP synthase complexes in vivo, and the exploration of interactions involving ATP synthase subunits by fluorescence resonance energy transfer (FRET).

A comparative trial of liver biopsy needles.

A sheathed needle (Tru-Cut) was compared with a suction biopsy needle (Menghini) in a randomised prospective trial over 18 months to determine whether the former offered any special advantages in routine percutaneous liver biopsy. Seventy-seven consecutive biopsies were performed by a single operator. Although biopsy fragmentation was commoner with the suction needle, the length and volume of the largest core obtained was similar to results with the sheathed needle. Cytology provided useful additional information with the Menghini technique. The suction needle was repeatedly reusable and considerably cheaper than the sheathed needle, which may be used once only.

Serum bile acids in patients with hyperlipidaemia.

Individual serum bile acids were analysed by an improved gas liquid chromatography method in 12 patients with primary hyperlipidaemia. Total serum bile acid concentrations were raised in 10 subjects. Ursodeoxycholic acid was found in all 12 patients. It was present in significantly greater concentrations, accounted for a greater proportion of the total serum bile acids, and occurred more frequently than in patients with various forms of hepatobiliary disease. Patients with hyperlipidaemia had proportionately less deoxycholic acid than controls but more than patients with liver disease. There was proportionately less chenodeoxycholic acid in patients with hypercholesterolaemia, in whom the primary bile acid ratio was raised.

Sensitivity of Helicobacter pylori to metronidazole.

Gastric antral forceps biopsies taken at gastroscopy were cultured for Helicobacter pylori and tested for anti-microbial sensitivity. Using micro-aerophilic culture, and disc testing or E-testing, there was 98-100% sensitivity to amoxycillin, tetracycline, clarithromycin and erythromycin. However, there was apparent resistance to metronidazole in 19 of 102 samples (19%). When sensitivity by E-testing was performed with preliminary anaerobic culture for 24 h only two of 94 samples (2%) showed resistance. In 37 cultures both micro-aerophilic disc testing and anaerobic then micro-aerophilic E-testing were conducted. Eight cultures showed resistance upon disc testing (MIC > 5 mg/l) but all of these organisms were sensitive on E-testing (MIC 0.003-0.5 mg/l). Metronidazole may be used with confidence in eradication regimes.

The use of timing behaviors in animals and humans to detect drug and/or toxicant effects.

Behavioral paradigms applicable for use in both human and nonhuman subjects for investigating aspects of timing behavior are presented with a view towards exploring their strengths, weaknesses, and utility in a variety of experimental situations. Tri-peak, peak interval, differential reinforcement of low rate responding, and temporal response differentiation procedures are highlighted. In addition, the application of timing tasks in preclinical and clinical settings is discussed: pharmacological manipulations are providing information on the neurotransmitters involved and species differences; normative data for children are being developed; and noninvasive imaging procedures are being employed in adult human subjects to explore the involvement of specific brain areas.

High-yielding repetitive somatic embryogenesis and plant recovery in a selected tea clone, 'TRI-2025', by temporary immersion.

Methods for improving the efficiency of repetitive somatic embryogenesis and plant recovery from somatic embryos of clonal tea, TRI 2025 [Camellia sinensis (L.) O. Kuntze] were investigated by optimising the immersion frequencies of the explants using a modified temporary immersion system (TIS). The relative efficiencies of three conventional methods for multiplying embryos were compared with the temporary immersion method. The highest rate of multiplication of secondary embryos (24-fold) was achieved using the TIS. By controlling the immersion cycles, we achieved more consistent, synchronised multiplication and embryo development with a high level of plant recovery. A one-step computer-programmed immersion protocol based on a single, simple medium with no growth regulators was developed, enabling multiplication, maturation, germination and plant recovery within 17 weeks. Plantlets recovered through this method were hardy, with 2- to 5-cm-long shoots containing a minimum of 2-4 lush green leaves and a well-formed taproot. Callus formation, hyperhydricity and other developmental abnormalities were not observed at any stage in the process. Plantlets produced using this method were successfully acclimatised to glasshouse conditions. This protocol avoids culture transfers, and thus minimises the risk of contamination and reduces labour costs. This technique could have significant commercial implications in tea propagation as it has the potential for large-scale production with considerably reduced production costs.

A parametric image technique for the assessment of oesophageal function.

An existing technique for the presentation of oesophageal transit studies has been further developed and applied to conventional radionuclide data. The spatial and temporal information contained in the original dynamic study is compressed to a single image, showing the linear distribution of activity down the oesophagus throughout the study. This parametric image contains all the useful information concerning the motion of the bolus, and is particularly useful for depicting the complex motion of a fragmented bolus. The technique has been shown to be of value in patients with a variety of oesophageal disorders.

Preferences for fixed and variable food sources: variability in amount and delay.

Much research has focused on the effects of environmental variability on foraging decisions. However, the general pattern of preference for variability in delay to reward and aversion to variability in amount of reward remains unexplained a either a mechanistic or a functional level. Starlings' preferences between a fixed and a variable option were studied in two treatments, A and D. The fixed option was the same in both treatments (20-s fixed-interval delay, five units food). In Treatment A the variable option gave two equiprobable amounts of food (20-s delay, three or seven units) and in D it gave two equiprobable delays to food (2.5-s or 60.5-s delays, five units). In both treatments the programmed ratio [amount/(intertrial interval+latency+delay)] in the fixed option equaled the arithmetic mean of the two possible ratios in the variable option (ITI = 40 s, latency = 1 s). The variable option was strongly preferred in Treatment D and was weakly avoided in Treatment A. These results are discussed in the light of two theoretical models, a form of constrained rate maximization and a version of scalar expectancy theory. The latter accommodates more of the data and is based on independently verifiable assumptions, including Weber's law.