Catastrophic drug errors involving tranexamic acid administered during spinal anaesthesia.

We have reviewed accidental spinal administration of tranexamic acid. We performed a MEDLINE search of cases of administration of tranexamic acid during epidural or spinal anaesthesia between 1960 and 2018. No reports of epidural administration were identified. We identified 21 cases of spinal tranexamic acid administration. Life-threatening neurological and/or cardiac complications, requiring resuscitation and/or intensive care, occurred in 20 patients; 10 patients died. We used a Human Factors Analysis Classification System model to analyse any contributing factors, and the reports were also assessed using four published recommendations for the reduction in neuraxial drug error. In 20 cases, ampoule error was the cause; in the last case a spinal catheter was mistaken for an intravenous catheter. All were classified as skill-based errors. Several human factors related to organisational policy; dispensing and storage of drugs and preparation for spinal anaesthesia tasks were present. All errors could have been prevented by implementing the four published recommendations.

Sex-related differences in the thanatomicrobiome in postmortem heart samples using bacterial gene regions V1-2 and V4.

Recent studies have revealed distinct thanatomicrobiome (microbiome of death) signatures in human body sites after death. Thanatomicrobiome studies suggest that microbial succession after death may have the potential to reveal important postmortem biomarkers for the identification of time of death. We surveyed the postmortem microbiomes of cardiac tissues from 10 corpses with varying times of death (6-58 h) using amplicon-based sequencing of the 16S rRNA gene' V1-2 and V4 hypervariable regions. The results demonstrated that amplicons had statistically significant (P < 0·05) sex-dependent changes. Clostridium sp., Pseudomonas sp., Pantoea sp. and Streptococcus sp. had the highest enrichment for both V1-2 and V4 regions. Interestingly, the results also show that V4 amplicons had higher abundance of Clostridium sp. and Pseudomonas sp. in female hearts compared to males. In addition, Streptococcus sp. was solely found in male heart samples. The distinction between sexes was further supported by principle coordinate analysis, which revealed microbes in female hearts formed a distinctive cluster separate from male cadavers for both hypervariable regions. This study provides data that demonstrates that two hypervariable regions show discriminatory power for sex differences in postmortem heart samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings represent preliminary data of the first thanatomicrobiome investigation of a comparison between 16S rRNA gene V1-2 and V4 amplicon signatures in corpse heart tissues. The results demonstrated that V4 hypervariable region amplicons had statistically significant (P < 0·05) sex-dependent microbial diversity. For example, Streptococcus sp. was solely found in male postmortem heart tissues. Interestingly, the results also show that V4 amplicons had higher abundance of Clostridium sp. and Pseudomonas sp. in female heart tissues compared to males. The finding of Clostridium sp. supports the postmortem clostridium effect in corpse heart tissues.

Requiem for Nigro or is anal squamous carcinoma still a surgical problem: Abdominoperineal excision rather than a defunctioning stoma?

BACKGROUND: Combined multimodal treatment (CMT) is the preferred treatment for anal squamous carcinoma with radical surgery reserved for treatment failure. Some patients require a defunctioning stoma prior to CMT. Successful closure of such a stoma is unlikely. Abdominoperineal excision (APE) may be suitable as primary treatment in these patients. METHOD: A retrospective review of all patients with anal squamous carcinoma was undertaken. Patients who required defunctioning colostomies prior to CMT were analysed for potential resectability of tumour prior to CMT and rate of permanent stoma. OBJECTIVE: To evaluate organ preservation in the treatment of anal squamous cancer and the closure rate of pre-treatment, temporary diverting colostomy, thereby assessing whether APE could be offered as primary treatment in those requiring a pre-treatment colostomy. RESULTS: One hundred and twenty-five patients were included of which 58 were males. The mean age was 56 years. 107 were treated with curative intent. Six received primary APE and 12 salvage APE. Thirty (22 males) required pretreatment diverting colostomies. Three (10%) stomas were successfully reversed. Forty-eight (38%) of the 125 completed treatment with a permanent colostomy. Six patients who needed a stoma prior to CMT were deemed resectable. CONCLUSION: Organ preservation was not possible in about a third of patients. Defunctioning stomas prior to CMT were likely to be permanent. We propose that APE could be considered as an alternative in selective cases where the tumour is resectable with low morbidity and a stoma is indicated.

Population differentiation and behavioural association of the two 'personality' genes DRD4 and SERT in dunnocks (Prunella modularis).

Quantifying the variation in behaviour-related genes within and between populations provides insight into how evolutionary processes shape consistent behavioural traits (i.e. personality). Deliberate introductions of non-native species offer opportunities to investigate how such genes differ between native and introduced populations and how polymorphisms in the genes are related to variation in behaviour. Here, we compared the genetic variation of the two 'personality' genes, DRD4 and SERT, between a native (United Kingdom, UK) and an introduced (New Zealand, NZ) population of dunnocks, Prunella modularis. The NZ population showed a significantly lower number of single nucleotide polymorphisms (SNPs) compared to the UK population. Standardized F'st estimates of the personality genes and neutral microsatellites indicate that selection (anthropogenic and natural) probably occurred during and post the introduction event. Notably, the largest genetic differentiation was found in the intronic regions of the genes. In the NZ population, we also examined the association between polymorphisms in DRD4 and SERT and two highly repeatable behavioural traits: flight-initiation distance and mating status (promiscuous females and cobreeding males). We found 38 significant associations (for different allele effect models) between the two behavioural traits and the studied genes. Further, 22 of the tested associations showed antagonistic allele effects for males and females. Our findings illustrate how introduction events and accompanying ecological changes could influence the genetic diversity of behaviour-related genes.

Microbial Signatures of Cadaver Gravesoil During Decomposition.

Genomic studies have estimated there are approximately 10(3)-10(6) bacterial species per gram of soil. The microbial species found in soil associated with decomposing human remains (gravesoil) have been investigated and recognized as potential molecular determinants for estimates of time since death. The nascent era of high-throughput amplicon sequencing of the conserved 16S ribosomal RNA (rRNA) gene region of gravesoil microbes is allowing research to expand beyond more subjective empirical methods used in forensic microbiology. The goal of the present study was to evaluate microbial communities and identify taxonomic signatures associated with the gravesoil human cadavers. Using 16S rRNA gene amplicon-based sequencing, soil microbial communities were surveyed from 18 cadavers placed on the surface or buried that were allowed to decompose over a range of decomposition time periods (3-303 days). Surface soil microbial communities showed a decreasing trend in taxon richness, diversity, and evenness over decomposition, while buried cadaver-soil microbial communities demonstrated increasing taxon richness, consistent diversity, and decreasing evenness. The results show that ubiquitous Proteobacteria was confirmed as the most abundant phylum in all gravesoil samples. Surface cadaver-soil communities demonstrated a decrease in Acidobacteria and an increase in Firmicutes relative abundance over decomposition, while buried soil communities were consistent in their community composition throughout decomposition. Better understanding of microbial community structure and its shifts over time may be important for advancing general knowledge of decomposition soil ecology and its potential use during forensic investigations.

Population structure within an alpine archipelago: strong signature of past climate change in the New Zealand rock wren (Xenicus gilviventris).

Naturally subdivided populations such as those occupying high-altitude habitat patches of the 'alpine archipelago' can provide significant insight into past biogeographical change and serve as useful models for predicting future responses to anthropogenic climate change. Among New Zealand's alpine taxa, phylogenetic studies support two major radiations: the first correlating with geological forces (Pliocene uplift) and the second with climatic processes (Pleistocene glaciations). The rock wren (Xenicus gilviventris) is a threatened alpine passerine belonging to the endemic New Zealand wren family (Acanthisittidae). Rock wren constitute a widespread, naturally fragmented population, occurring in patches of suitable habitat over c. 900 m in altitude throughout the length of the South Island, New Zealand. We investigated the relative role of historical geological versus climatic processes in shaping the genetic structure of rock wren (N = 134) throughout their range. Using microsatellites combined with nuclear and mtDNA sequence data, we identify a deep north-south divergence in rock wren (3.7 ± 0.5% at cytochrome b) consistent with the glacial refugia hypothesis whereby populations were restricted in isolated refugia during the Pleistocene c. 2 Ma. This is the first study of an alpine vertebrate to test and provide strong evidence for the glacial refugia hypothesis as an explanation for the low endemicity central zone known as the biotic 'gap' in the South Island of New Zealand.

Postglacial expansion and not human influence best explains the population structure in the endangered kea (Nestor notabilis).

Inferring past demography is a central question in evolutionary and conservation biology. It is, however, sometimes challenging to infer the processes that shaped the current patterns of genetic variation in endangered species. Population substructuring can occur as a result of survival in several isolated refugia and subsequent recolonization processes or via genetic drift following a population decline. The kea (Nestor notabilis) is an endemic parrot widely distributed in the mountains of the South Island of New Zealand that has gone through a major human-induced population decline during the 1860s-1970s. The aims of this study were to understand the glacial and postglacial history of kea and to determine whether the recent population decline played a role in the shaping of the current genetic variation. We examined the distribution of genetic variation, differentiation and admixture in kea using 17 microsatellites and the mitochondrial control region. Mitochondrial data showed a shallow phylogeny and a genetic distinction between the North and South of the range consistent with the three genetic clusters identified with microsatellite data. Both marker types indicated an increase in genetic isolation by geographic distance. Approximate Bayesian Computation supported a scenario of postglacial divergence from a single ancestral glacial refugium, suggesting that the contemporary genetic structure has resulted from recolonization processes rather than from a recent population decline. The recent evolutionary origin of this genetic structure suggests that each genetic cluster does not need to be considered as independent conservation units.

Extensive variation at MHC DRB in the New Zealand sea lion (Phocarctos hookeri) provides evidence for balancing selection.

Marine mammals are often reported to possess reduced variation of major histocompatibility complex (MHC) genes compared with their terrestrial counterparts. We evaluated diversity at two MHC class II B genes, DQB and DRB, in the New Zealand sea lion (Phocarctos hookeri, NZSL) a species that has suffered high mortality owing to bacterial epizootics, using Sanger sequencing and haplotype reconstruction, together with next-generation sequencing. Despite this species' prolonged history of small population size and highly restricted distribution, we demonstrate extensive diversity at MHC DRB with 26 alleles, whereas MHC DQB is dimorphic. We identify four DRB codons, predicted to be involved in antigen binding, that are evolving under adaptive evolution. Our data suggest diversity at DRB may be maintained by balancing selection, consistent with the role of this locus as an antigen-binding region and the species' recent history of mass mortality during a series of bacterial epizootics. Phylogenetic analyses of DQB and DRB sequences from pinnipeds and other carnivores revealed significant allelic diversity, but little phylogenetic depth or structure among pinniped alleles; thus, we could neither confirm nor refute the possibility of trans-species polymorphism in this group. The phylogenetic pattern observed however, suggests some significant evolutionary constraint on these loci in the recent past, with the pattern consistent with that expected following an epizootic event. These data may help further elucidate some of the genetic factors underlying the unusually high susceptibility to bacterial infection of the threatened NZSL, and help us to better understand the extent and pattern of MHC diversity in pinnipeds.

BAS: balanced acceptance sampling of natural resources.

To design an efficient survey or monitoring program for a natural resource it is important to consider the spatial distribution of the resource. Generally, sample designs that are spatially balanced are more efficient than designs which are not. A spatially balanced design selects a sample that is evenly distributed over the extent of the resource. In this article we present a new spatially balanced design that can be used to select a sample from discrete and continuous populations in multi-dimensional space. The design, which we call balanced acceptance sampling, utilizes the Halton sequence to assure spatial diversity of selected locations. Targeted inclusion probabilities are achieved by acceptance sampling. The BAS design is conceptually simpler than competing spatially balanced designs, executes faster, and achieves better spatial balance as measured by a number of quantities. The algorithm has been programed in an R package freely available for download.

Brachiobasilic fistula formation - single versus two stage procedure.

BACKGROUND: Brachial basilic (BB) fistulae are a form of vascular access for patients requiring dialysis. They are indicated when the cephalic vein is unsuitable for use. This fistula can be created with either a single stage or a two stage procedure. We aimed to compare the two techniques. METHODS: 73 BB fistulae (29 single and 44 two-stage) were created over a 5-year period (2003-2008). Data including sex, age, dialysis and diabetic status was collected from the case notes. Patency and time to maturity data was collected prospectively on an electronic database within the dialysis unit. RESULTS: There was no significant difference in functional patency rates between the two methods. A significant difference was identified between patients who had their fistula created prior to starting dialysis compared to those who had their fistula created after starting dialysis, in both initial patency rate (p = 0.017) and long term survival of the fistulae (p = 0.002). CONCLUSION: We identified no significant difference of patency between the two methods. This implies that a single stage procedure has benefits, by offering a quicker form of vascular access. Patients who had their fistulae created prior to dialysis had improved patency rates.

Self-assembled hierarchical nanostructures composed of novel chalcopyrite nanosheets for photovoltaic properties.

Self-assembled nanostructures of CulnGaSe2 (CIGS) comprising of nanosheets with sheet thickness of 20 nm have been developed via one-step electrochemically alloying technique. These self-assembled nanoplates exhibit highly intersecting behavior and transform from CuSe to CIGS as the reduction potential was varied. The morphological analysis indicated that the process resulted in a progression of crystallites to a series of heavy dense intersecting nanoplates. Further analyses revealed that the nanostructures keep their integrity on heat treatment. The structure confirms the inclusion of Indium and Gallium at higher reduction potentials and its transition from pseudoamorphous to polycrystalline structure. A strong correlation between reduction potential, and the composition was established. The spectroscopic and optical spectra clearly prove that the direct band gap for the as-grown and annealed thin films, and appropriate for solar cell applications. These self-assembled dense interweaved nanoplates structure have not been observed previously in CIGS semiconductor system and have potential implications forenergy applications.

Measuring communicative participation using the FOCUS©: Focus on the Outcomes of Communication Under Six.

BACKGROUND: The FOCUS© is a new outcome tool for use by both parents and clinicians that measures changes in the communicative participation skills of preschool children. Changes in communicative participation skills as measured by the FOCUS were compared across three groups of children: those with speech impairments only (SI), those with language impairments only (LI) and those with both speech and language impairments (S/LI). METHODS: Participating families (n = 112, 75 male children) were recruited through 13 Canadian organizations. Children ranged from 10 months to 6 years 0 months (mean = 2.11 years; SD = 1.18 years) and attended speech-language intervention. Parents completed the FOCUS at the start and end of treatment. There were 23 children in the SI group, 62 children in the LI group and 27 children in the S/LI group. The average amount of the children's therapy varied from 7 to 10 h. RESULTS: The FOCUS captures changes in communicative participation for children with a range of communication disorder types and severities. All three groups of children made clinically important improvements according to their FOCUS scores (MCID ≥ 16 points). The FOCUS captured improvements in intelligibility, independent communication, play and socialization. CONCLUSIONS: The FOCUS measured positive changes in communicative participation skills for all three groups of children after 7-10 h of speech-language therapy. An outcome measure that targets only specific speech and language skills would miss many of the important social function changes associated with speech-language treatment.

Construct validity of the FOCUS© (Focus on the Outcomes of Communication Under Six): a communicative participation outcome measure for preschool children.

OBJECTIVE: The aim of this study was to establish the construct validity of the Focus on the Outcomes of Communication Under Six (FOCUS©). This measure is reflective of concepts in the International Classification of Functioning Disability and Health--Children and Youth framework. It was developed to capture 'real-world' changes (e.g. communicative participation) in preschoolers' communication following speech-language intervention. METHOD: A pre-post design was used. Fifty-two parents of 3- to 6-year-old preschoolers attending speech-language therapy were included as participants. Speech-language therapists provided individual and/or group intervention to preschoolers. Intervention targeted: articulation/phonology, voice/resonance, expressive/receptive language, play, and use of augmentative devices. Construct validity for communicative participation was assessed using pre-intervention and post-intervention parent interviews using the FOCUS© and the communication and socialization domains of the Vineland Adaptive Behavior Scales-II (VABS-II). RESULTS: Significant associations were found between the FOCUS©, measuring communicative participation, and the VABS-II domains for: (i) pre-intervention scores in communication (r = 0.53, P < 0.001; 95% CI 0.30-0.70) and socialization (r = 0.67, P < 0.001; 95% CI 0.48-0.80); (ii) change scores over-time in communication (r = 0.45, P < 0.001; 95% CI 0.201-0.65) and socialization (r = 0.39, P = 0.002; 95% CI 0.13-0.60); and (iii) scores at post-intervention for communication (r = 0.53, P < 0.001; 95% CI 0.30-0.70) and for socialization (r = 0.37, P = 0.003; 95% CI 0.11-0.50). CONCLUSIONS: The study provided evidence on construct validity of the FOCUS© for evaluating real-world changes in communication. We believe that the FOCUS© is a useful measure of communicative participation.

Validation of the Glasgow Facial Palsy Scale for the assessment of smile reanimation surgery in facial paralysis.

OBJECTIVES: To evaluate the Glasgow Facial Palsy Scale as a tool to assess facial reanimation surgery in facial palsy. Software analysis of digital video data is used to measure facial movements, comparing the affected to the normal side. We present the first use of the Glasgow Facial Palsy Scale following facial re-animation surgery. DESIGN: A comparison of the Glasgow Facial Palsy Scale against the Nottingham scoring system. Subjects undergoing unilateral surgical smile reanimation procedures were selected. Comparison was made with the Nottingham facial palsy scale and the House-Brackmann Scale pre- and postoperatively. SETTING: Patients were recruited in the facial palsy clinic of Canniesburn Plastic Surgery Unit, Glasgow. PARTICIPANTS: Seven consecutive patients were selected who were due to undergo unilateral facial reanimation. MAIN OUTCOME MEASURES: The difference in pre- and post-surgical facial movement as measured using the Glasgow Facial Palsy Scale with this value being compared to that obtained using the Nottingham scoring system. Note was also taken of the correlation with House-Brackmann system and clinical correlation. RESULTS AND CONCLUSIONS: Statistical analysis indicated a linear relationship between the Glasgow Facial Palsy Scale and the Nottingham System. The Pearson correlation test was used to confirm the relationship between the two methods giving a result of -0.587, which indicates significant correlation between the two methods. We conclude that the Glasgow Facial Palsy Scale is a standardised objective method of assessing the change in facial movement following smile reanimation surgery. We commend it as a useful tool to objectively assess surgical results in this challenging field.

The use of telomere length in ecology and evolutionary biology.

The measurement of telomere length (TL) is a genetic tool that is beginning to be employed widely in ecological and evolutionary studies as marker of age and fitness. The adoption of this approach has been accelerated by the development of telomere quantitative PCR, which enables the screening of large numbers of samples with little effort. However, the measurement and interpretation of TL change need to be done with a necessary level of rigour that has thus far often been missing where this approach has been employed in an ecological and evolutionary context. In this article, we critically review the literature available on the relationship between TL, age and fitness. We seek to familiarize geneticists, ecologists and evolutionary biologists with the shortcomings of the methods and the most common mistakes made while analysing TL. Prevention of these mistakes will ensure accuracy, reproducibility and comparability of TL studies in different species and allow the identification of ecological and evolutionary principles behind TL dynamics.

Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine.

A DNA sequence coding for the immunogenic capsid protein VP3 of foot-and-mouth disease virus A12, prepared from the virion RNA, was ligated to a plasmid designed to express a chimeric protein from the Escherichia coli tryptophan promoter-operator system. When Escherichia coli transformed with this plasmid was grown in tryptophan-depleted media, approximately 17 percent of the total cellular protein was found to be an insoluble and stable chimeric protein. The purified chimeric protein competed equally on a molar basis with VP3 for specific antibodies to foot-and-mouth disease virus. When inoculated into six cattle and two swine, this protein elicited high levels of neutralizing antibody and protection against challenge with foot-and-mouth disease virus.

A retrospective study of tuberculosis outcomes in Gulf Province, Papua New Guinea.

SETTING: Gulf Province, a rural area of mainland Papua New Guinea, is known to have one of the highest burdens of tuberculosis (TB) in the country. OBJECTIVES: To describe the characteristics and outcomes of TB patients registered for first-line treatment in Kerema General Hospital in Gulf Province between January and December 2016. DESIGN: This was a retrospective cohort study using routinely collected programme data. RESULTS: Of 347 cases with a recorded TB site, 54% were male and 32% were aged <15 years. No human immunodeficiency virus (HIV) status was recorded for 51% of cases. TB was bacteriologically confirmed in 23% of cases. Among the cohort, there were 145 extrapulmonary TB cases (42%); the site of disease was unknown in 56% of these cases. Of the 297 cases with treatment outcome evaluated, 56% had a favourable outcome and 26% were lost to follow-up. On multivariable analysis, extrapulmonary TB (adjusted OR [aOR] 0.51, 95%CI 0.30-0.88, P = 0.02) and bacteriologically confirmed TB (aOR 0.40, 95%CI 0.21-0.77, P < 0.01) were associated with decreased odds of an unfavourable treatment outcome. CONCLUSION: The study findings highlight the need to improve TB diagnosis, access to HIV testing, treatment adherence, patient support and the quality of TB programme data in Gulf Province.

Hue-specific colour memory impairment in an individual with intact colour perception and colour naming.

Cases of hue-selective dyschomatopsias, together with the results of recent optical imaging studies [Xiao, Y., Casti, A. R. R., Xiao, J., & Kaplan, E. (2006). A spatially organized representation of colour in macaque primary visual cortex. Perception, 35, ECVP Abstract Supplement; Xiao, Y., Wang, Y., & Felleman, D. J. (2003). A spatially organized representation of colour in macaque cortical area V2. Nature, 421, 535-539], have provided support for the idea that different colours are processed in spatially distinct regions of extrastriate cortex. In the present report, we provide evidence suggesting that a similar, but distinct, map may exist for representations of colour in memory. This evidence comes from observations of a young woman (QP) who demonstrates an isolated deficit in colour memory secondary to a concussive episode. Despite having normal colour perception and colour naming skills, and above-average memory skills in other domains, QP's ability to recall visually encoded colour information over short retention intervals is dramatically impaired. Her long-term memory for colour and her colour imagery skills are also abnormal. Surprisingly, however, these impairments are not seen with all hues; specifically, her ability to remember or imagine blue shades is spared. This interesting case contributes to the literature suggesting that colour perception, naming, and memory can be clinically dissociated, and provides insights into the organization of colour information in memory.