Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

Comparison of nine different methods to assess fish communities in lentic flood-plain habitats.

This study compares the effectiveness and representativeness of electrofishing, snorkelling, seining, baited lift netting, multi-mesh gillnetting, baited fish traps, fyke netting, angling and longline fishing, considering three typical lentic flood-plain habitats at different times of day. Electrofishing was by far the most effective method yielding highest species richness, species trait representation and catch per unit of effort (CPUE), followed by seining. For single species like dace Leuciscus leuciscus, European ruffe Gymnocephalus cernua, common bream Abramis brama and silver bream Blicca bjoerkna, seining was more effective than electrofishing. With both methods, some species were more consistently caught during night, dusk or dawn than during daylight. All other methods tested cannot be generally recommended for fish community assessments in shallow backwaters due to their low representativeness of species inventory and generally low CPUE. Based on these results, electrofishing of 30 m transect replicates at different times of day for monitoring the fish community in shallow backwaters, can be recommended, enabling the maximum possible comparability to adjacent river habitats. Seining should be considered as an alternative if accessibility of habitats is restricted or electrofishing is prohibited. The 25 species detected in the backwaters also suggest that these habitats contribute a large proportion of fish diversity and should be included in standard assessments of river ecological status.

Fracturing across the multi-scales of diverse materials.

Everyone has to deal with fracturing of materials at one level or another, beginning from normal household chores and extending to the largest scale of observations reported for catastrophic events occurring on a geological level or even expanded to events in outer space. Such wide perspective is introduced in the current introduction of this theme issue. The follow-on organization of technical articles provides a flavour of the range in size scales at which fracturing occurs in a wide diversity of materials-from 'fracking' oil extraction and earth moving to laboratory testing of rock material and extending to the cracking of tooth enamel. Of important scientific interest are observations made and analysed at the smallest dimensions corresponding to the mechanisms by which fracture is either enhanced or hindered by permanent deformation or other processes. Such events are irrevocably linked to the atomic structure in all engineering materials, a sampling of which is presented, including results for crystalline and amorphous materials. Hooray for the broad subject description that is hoped to be appealing to the interested reader.

Clinical effectiveness of a silicone foam dressing for the prevention of heel pressure ulcers in critically ill patients: Border II Trial.

OBJECTIVE: Critically ill patients are at high risk of developing pressure ulcers (PU), with the sacrum and heels being highly susceptible to pressure injuries. The objective of our study was to evaluate the clinical effectiveness of a new multi-layer, self-adhesive soft silicone foam heel dressing to prevent PU development in trauma and critically ill patients in the intensive care unit (ICU). METHOD: A cohort of critically ill patients were enrolled at the Royal Melbourne Hospital. Each patient had the multi-layer soft silicone foam dressing applied to each heel on admission to the emergency department. The dressings were retained with a tubular bandage for the duration of the patients' stay in the ICU. The skin under the dressings was examined daily and the dressings were replaced every three days. The comparator for our cohort study was the control group from the recently completed Border Trial. RESULTS: Of the 191 patients in the initial cohort, excluding deaths, loss to follow-up and transfers to another ward, 150 patients were included in the final analysis. There was no difference in key demographic or physiological variables between the cohorts, apart from a longer ICU length of stay for our current cohort. No PUs developed in any of our intervention cohort patients compared with 14 patients in the control cohort (n=152; p<0.001) who developed a total of 19 heel PUs. CONCLUSION: We conclude, based on our results, that the multi-layer soft silicone foam dressing under investigation was clinically effective in reducing ICU-acquired heel PUs. The findings also support previous research on the clinical effectiveness of multi-layer soft silicone foam dressings for PU prevention in the ICU.

Prevalence of extended-spectrum ß-lactamase-producing Enterobacterales and carbapenemase-resistant Enterobacterales in British military cohorts.

INTRODUCTION: Travel to resource-limited settings is a known risk for acquisition of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) and carbapenem-resistant Enterobacterales (CRE), which are both associated with increased morbidity and mortality. We investigated the ESBL-PE and CRE baseline prevalence in British service personnel (SP). METHODS: SP provided faecal samples for research projects in several different settings, between September 2021 and April 2022. Bacterial colonies from faecal isolates were recovered from incubated ChromID ESBL plates (bioMérieux, Marcy-l'Étoile, France) and DNA extracted using Qiagen DNeasy extraction kits (Qiagen, UK). PCR to identify ß-lactamase and CRE encoding genes was performed using the Rotor-Gene Q (RGQ) (Qiagen, UK), with positivity detected by RGQ software. Phenotypic assessment of antimicrobial susceptibility was not performed. RESULTS: Out of 250 personnel approached, 239 (85.5% men, median (IQR) age 31 (26-37) years) provided faecal samples suitable for analysis. The ESBL prevalence was 40/239 (16.7%), with ESBL-producing Escherichia coli detected in 39 (16.3%) samples and ESBL-producing Klebsiella pneumoniae in 1 (0.4%) sample. Combinations including Temoniera, sulfhydryl reagent variable (SHV), cefotaxime hydrolysing ß-lactamase (Munich) (CTX-M) 1 and CTX-M 9 genes were detected in 18 (7.5%), 33 (13.8%) 16 (6.7%) and 8 (3.3%) samples, respectively. E. coli samples had mixtures of all four genotypes with SHV predominating. One (0.4%) sample carried all four gene types and the only K. pneumoniae sample carried a single SHV gene. No CRE were detected. CONCLUSIONS: The prevalence of ESBL-PE in cohorts of SP closely matches that of civilian populations in England; however, we noted differences in ESBL genotype distribution. Potential exposure risks for SP from international travel and occupational trauma emphasise the need for repeated surveillance to characterise and detect changes in acquisition epidemiology and carriage of ESBL. Such prospective data have important antimicrobial stewardship implications in optimising clinical outcomes, controlling resistance and guiding empirical antibiotic formulary policy recommendations.

Poor numeracy skills are associated with glycaemic control in Type 1 diabetes.

AIMS: To assess the numeracy and literacy skills of individuals with Type 1 diabetes and determine if there is a relationship with achieved glycaemic control independent of their duration of diabetes, diabetes education, demographic and socio-economic factors. METHODS: One hundred and twelve patients completed the study (mean current age 43.8 ± 12.5 years, 47% male, mean duration of diabetes 22.0 ± 13.2 years) out of 650 randomly selected patients from the Bournemouth Diabetes and Endocrine Centre's diabetes register. The Skills for Life Initial Assessments were used to measure numeracy and literacy. These indicate skills levels up to level 2, equivalent to the national General Certificate of Secondary Education grades A*-C. HbA(1c) was also measured. Pearson's correlation was used to measure the correlation of numeracy and literacy scores with HbA(1c.) To compare mean HbA(1c) between those with or without level 2 skills, t-tests were used, and multiple linear regression was used to investigate whether any differences were independent of duration of diabetes, diabetes education, demographic and socio-economic factors. RESULTS: Literacy was not associated with achieved HbA(1c). In contrast, participants with numeracy skills at level 2 or above achieved an HbA(1c) lower than those with numeracy skills below level 2 (P = 0.027). Although higher socio-economic status was associated with lower mean HbA(1c) , the relationship between numeracy and HbA(1c) appeared to be independent of socio-economic factors. CONCLUSIONS: Low numeracy skills were adversely associated with diabetes control. Assessment of numeracy skills may be relevant to the structure of diabetes education programmes.

HbA1c 3 months after diagnosis predicts premature mortality in patients with new onset type 2 diabetes.

AIMS: To determine 5-year mortality rates, following the diagnosis of Type 2 diabetes, in a large local cohort of individuals with new onset of Type 2 diabetes seen within a few weeks of diagnosis in a single, community-based education programme. METHODS: We reviewed referrals for people with Type 2 diabetes to our service over 5 years from 1999 to 2003 and determined, via regression analysis, which factors contributed significantly to mortality rates up to the end of 2007. RESULTS: A total of 3781 new referrals were reviewed with an approximate doubling of referral rates over 5 years (546 in 1999-997 in 2003). Although the number of people developing the condition has increased, mortality rates over the 5 years from diagnosis has fallen from 11% in 1999-9% in 2003 (P < 0.005) Age at diagnosis was the strongest predictor of mortality (P < 0.001) but HbA(1c) at 3 months after diagnosis (P < 0.001), systolic (P < 0.001) and diastolic (P = 0.05) blood pressure, smoking status (P < 0.001) and gender (P = 0.04) were also significant predictors. CONCLUSIONS: Our retrospective analysis adds weight to evidence suggesting that referral rates for people with Type 2 diabetes are increasing rapidly and that mortality rates are reducing but that the reasons for this are multifactorial. In addition to blood pressure, smoking and gender, the HbA(1c) achieved 3 months after the initial diagnosis also appears to predict subsequent mortality. It may be appropriate to consider early and intensive intervention for individuals with new onset type 2 diabetes.

Validation of the Full Outline of Unresponsiveness (FOUR) Scale for conscious state in the emergency department: comparison against the Glasgow Coma Scale.

OBJECTIVES: To determine (a) the inter-rater reliability of pairs of emergency doctors' and/or nurses' ratings of the Glasgow Coma Scale (GCS) and the Full Outline of Unresponsiveness (FOUR) Scale in emergency department (ED) patients, (b) the concurrent validity of the FOUR Scale using the GCS as the reference scale and (c) doctors' and nurses' knowledge and attitudes towards the GCS and FOUR Scale. METHODS: A prospective observational study was conducted using staff participants' ratings for a convenience sample of ED patients requiring quantification of conscious state. Participating doctors and nurses attended a formal training session on the correct use of the GCS and FOUR Scale. Pairs of clinicians then independently completed the GCS and FOUR Scale on patients within 5 min of each other. RESULTS: 140 clinicians were recruited and trained in the use of the GCS and FOUR Scale. A total of 217 observations were performed on 203 patients presenting to the ED with various conditions. The inter-rater reliability for the FOUR Scale was greater than that of the GCS (FOUR: к = 0.76, p < 0.01; GCS: к = 0.59, p < 0.01). The reliability for both the GCS and the FOUR Scale was poorest within doctor-nurse pairs. CONCLUSION: The FOUR Scale showed greater reliability than the GCS in ED patients using ED clinicians as raters. A larger study of ED patients is warranted to determine the predictive validity of the FOUR Scale and to further examine the reliability of the scale in various patient populations.

Causes of injuries in the mountains: a review of worldwide reports into accidents in mountaineering.

This review presents a selection of sources from the UK and around the world that have reported on both incidents and accidents in the mountains. Common themes are extracted to illustrate the circumstances under which accidents, injuries and fatalities occur and the underlying factors that have contributed to incidents in the first place. There is an attempt to dispel some 'myths' surrounding accidents in mountain based activities. The purpose of highlighting these issues is to allow those undertaking them to understand where the greatest risks lie. This enables the individual, team leaders, rescue services and those involved in the overall management of wilderness areas to plan accordingly, with the aim of reducing injuries and deaths.

Satisfaction with the emergency department environment decreases with length of stay.

OBJECTIVE: To determine the emergency department (ED) environmental factors associated with patient satisfaction. METHODS: A prospective, observational study in a university-affiliated tertiary-referral ED and associated observation unit (OU). The ED environment was evaluated with a structured questionnaire, scored using a 100-mm visual analogue scale. Patients who stayed in the ED over 8 h (long-stay ED; LSED) were compared with those who stayed less than 4 h (short-stay ED; SSED) and with a control group admitted to the OU. RESULTS: A total of 233 patients was enrolled, overall satisfaction in SSED was 81% (95% CI 70.1 to 88.7), 69% in LSED (95% CI 57.4 to 78.7) and 84% in OU (95% CI 73.6 to 91.0). The most important environmental factors were cleanliness (median importance 95, interquartile range (IQR) 81-98) and communication with medical staff (94, IQR 80-98) and family (92, IQR 74-98). The least important factors were access to nature (38, IQR 19-65), a natural light source (50, IQR 24-74) and ability to sit out of bed (52, IQR 26-75). Factors rated high for importance but low for satisfaction were ED noise levels (median difference 40, IQR 3-70), ED trolley comfort (19, IQR 6-50) and food quality (12, IQR -4-29). CONCLUSION: Patients who spend over 8 h in the ED are less satisfied with their environment than either those who spend less than 4 h or patients in an OU. Importantly, distinct, amenable factors can be identified. These should be addressed to improve patients' overall ED management and satisfaction.

Mutations in the SUP-PF-1 locus of Chlamydomonas reinhardtii identify a regulatory domain in the beta-dynein heavy chain.

We have characterized a group of regulatory mutations that alter the activity of the outer dynein arms. Three mutations were obtained as suppressors of the paralyzed central pair mutant pf6 (Luck, D.J.L., and G. Piperno. 1989. Cell Movement. pp. 49-60), whereas two others were obtained as suppressors of the central pair mutant pfl6. Recombination analysis and complementation tests indicate that all five mutations are alleles at the SUP-PF-1/ODA4 locus and that each allele can restore motility to radial spoke and central pair defective strains. Restriction fragment length polymorphism analysis with a genomic probe for the beta-dynein heavy chain (DHC) gene confirms that this locus is tightly linked to the beta-DHC gene. Although all five mutant sup-pf-1 alleles alter the activity of the outer dynein arm as assayed by measurements of flagellar motility, only two alleles have a discernable polypeptide defect by SDS-PAGE. We have used photolytic and proteolytic cleavage procedures to localize the polypeptide defect to an approximately 100-kD domain downstream from the last putative nucleotide binding site. This region is encoded by approximately 5 kb of genomic DNA (Mitchell, D.R., and K. Brown. 1994. J. Cell Sci. 107:653-644). PCR amplification of wild-type and mutant DNA across this region identified one PCR product that was consistently smaller in the sup-pf-1 DNA. Direct DNA sequencing of the PCR products revealed that two of the sup-pf-1 mutations are distinct, in-frame deletions. These deletions occur within a region that is predicted to encode a small alpha-helical coiled-coil domain of the beta-DHC. This domain may play a role in protein-protein interactions within the outer dynein arm. Since both the size and location of this domain have been conserved in all axonemal and cytoplasmic DHCs sequenced to date, it presumably performs a common function in all dynein isoforms.

Domains in the 1alpha dynein heavy chain required for inner arm assembly and flagellar motility in Chlamydomonas.

Flagellar motility is generated by the activity of multiple dynein motors, but the specific role of each dynein heavy chain (Dhc) is largely unknown, and the mechanism by which the different Dhcs are targeted to their unique locations is also poorly understood. We report here the complete nucleotide sequence of the Chlamydomonas Dhc1 gene and the corresponding deduced amino acid sequence of the 1alpha Dhc of the I1 inner dynein arm. The 1alpha Dhc is similar to other axonemal Dhcs, but two additional phosphate binding motifs (P-loops) have been identified in the NH(2)- and COOH-terminal regions. Because mutations in Dhc1 result in motility defects and loss of the I1 inner arm, a series of Dhc1 transgenes were used to rescue the mutant phenotypes. Motile cotransformants that express either full-length or truncated 1alpha Dhcs were recovered. The truncated 1alpha Dhc fragments lacked the dynein motor domain, but still assembled with the 1beta Dhc and other I1 subunits into partially functional complexes at the correct axoneme location. Analysis of the transformants has identified the site of the 1alpha motor domain in the I1 structure and further revealed the role of the 1alpha Dhc in flagellar motility and phototactic behavior.

Production of calves from G1 fibroblasts.

Since the landmark study of Wilmut et al. describing the birth of a cloned lamb derived from a somatic cell nucleus, there has been debate about the donor nucleus cell cycle stage required for somatic cell nuclear transfer (NT). Wilmut et al. suggested that induction of quiescence by serum starvation was critical in allowing donor somatic cells to support development of cloned embryos. In a subsequent report, Cibelli et al. proposed that G0 was unnecessary and that calves could be produced from actively dividing fibroblasts. Neither study conclusively documented the importance of donor cell cycle stage for development to term. Other laboratories have had success with NT in several species, and most have used a serum starvation treatment. Here we evaluate methods for producing G0 and G1 cell populations and compare development following NT. High confluence was more effective than serum starvation for arresting cells in G0. Pure G1 cell populations could be obtained using a "shake-off" procedure. No differences in in vitro development were observed between cells derived from the high-confluence treatment and from the "shake-off" treatment. However, when embryos from each treatment were transferred to 50 recipients, five calves were obtained from embryos derived from "shake-off" cells, whereas no embryos from confluent cells survived beyond 180 days of gestation. These results indicate that donor cell cycle stage is important for NT, particularly during late fetal development, and that actively dividing G1 cells support higher development rates than cells in G0.

The Chlamydomonas Dhc1 gene encodes a dynein heavy chain subunit required for assembly of the I1 inner arm complex.

Multiple members of the dynein heavy chain (Dhc) gene family have been recovered in several organisms, but the relationships between these sequences and the Dhc isoforms that they encode are largely unknown. To identify Dhc loci and determine the specific functions of the individual Dhc isoforms, we have screened a collection of motility mutants generated by insertional mutagenesis in Chlamydomonas. In this report, we characterize one strain, pf9-3, in which the insertion event was accompanied by a deletion of approximately 13 kb of genomic DNA within the transcription unit of the Dhc1 gene. Northern blot analysis confirms that pf9-3 is a null mutation. Biochemical and structural studies of isolated axonemes demonstrate that the pf9-3 mutant fails to assemble the I1 inner arm complex, a two-headed dynein isoform composed of two Dhcs (1 alpha and 1 beta) and three intermediate chains. To determine if the Dhc1 gene product corresponds to one of the Dhcs of the I1 complex, antibodies were generated against a Dhc1-specific peptide sequence. Immunoblot analysis reveals that the Dhc1 gene encodes the 1 alpha Dhc subunit. These studies thus, identify the first inner arm Dhc locus to be described in any organism and further demonstrate that the 1 alpha Dhc subunit plays an essential role in the assembly of the I1 inner arm complex.

Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in Chlamydomonas.

A second cytoplasmic dynein heavy chain (cDhc) has recently been identified in several organisms, and its expression pattern is consistent with a possible role in axoneme assembly. We have used a genetic approach to ask whether cDhc1b is involved in flagellar assembly in Chlamydomonas. Using a modified PCR protocol, we recovered two cDhc sequences distinct from the axonemal Dhc sequences identified previously. cDhc1a is closely related to the major cytoplasmic Dhc, whereas cDhc1b is closely related to the minor cDhc isoform identified in sea urchins, Caenorhabditis elegans, and Tetrahymena. The Chlamydomonas cDhc1b transcript is a low-abundance mRNA whose expression is enhanced by deflagellation. To determine its role in flagellar assembly, we screened a collection of stumpy flagellar (stf) mutants generated by insertional mutagenesis and identified two strains in which portions of the cDhc1b gene have been deleted. The two mutants assemble short flagellar stumps (<1-2 micrometer) filled with aberrant microtubules, raft-like particles, and other amorphous material. The results indicate that cDhc1b is involved in the transport of components required for flagellar assembly in Chlamydomonas.

Sequence of lamprey vitellogenin. Implications for the lipovitellin crystal structure.

The amino acid sequence of lamprey vitellogenin has been predicted from the nucleotide sequence of cloned cDNA. The sites of proteolytic cleavage that produce the lipovitellin complex from the vitellogenin have been located by comparing the N-terminal sequences of two lamprey lipovitellin polypeptides with the predicted sequence. These results also confirm that the vitellogenin sequence derived here corresponds to the lipovitellin complex for which the crystal structure has been solved previously. Predictions of secondary structure indicate that the region most likely to correspond to the large alpha-helical domain of the crystallographic model consists of vitellogenin residues 300 to 600. Similar to the lipovitellins of Xenopus laevis, lamprey lipovitellin appears to lack approximately 200 C-terminal residues that are present in vitellogenin. However, the lamprey lipovitellin differs from those of Xenopus and chicken in two respects. First, most of the serine-rich domain that is present as the phosvitin polypeptide in the lipovitellins of the higher vertebrates appears to be lost in the maturation of lamprey vitellogenin to lipovitellin. Second, the domains that constitute the large lipovitellin-1 polypeptide in Xenopus and chicken are present in two polypeptides in lamprey, owing to an additional proteolytic processing event.

The dynein gene family in Chlamydomonas reinhardtii.

To correlate dynein heavy chain (Dhc) genes with flagellar mutations and gain insight into the function of specific dynein isoforms, we placed eight members of the Dhc gene family on the genetic map of Chlamydomonas. Using a PCR-based strategy, we cloned 11 Dhc genes from Chlamydomonas. Comparisons with other Dhc genes indicate that two clones correspond to genes encoding the alpha and beta heavy chains of the outer dynein arm. Alignment of the predicted amino acid sequences spanning the nucleotide binding site indicates that the remaining nine clones can be subdivided into three groups that are likely to include representatives of the inner-arm Dhc isoforms. Gene-specific probes reveal that each clone represents a single-copy gene that is expressed as a transcript of the appropriate size (> 13 kb) sufficient to encode a high molecular weight Dhc polypeptide. The expression of all nine genes is upregulated in response to deflagellation, suggesting a role in axoneme assembly or motility. Restriction fragment length polymorphisms between divergent C. reinhardtii strains have been used to place each Dhc gene on the genetic map of Chlamydomonas. These studies lay the groundwork for correlating defects in different Dhc genes with specific flagellar mutations.

Contribution of the V lambda light chain to the development of the primary antibody repertoire.

The experiments outlined here provide evidence that most VH gene families are expressed in association with either of three V lambda genes available in kappa-deficient mice, though their expression is nonrandom. An exclusive use of V lambda L-chain genes, where predominantly expressed V lambda 1 and V lambda 2 differ by only seven amino acid substitutions in the germline, results in a higher degree of self-reactive antibodies to conserved natural antigens like albumin, thyroglobulin, and stress proteins. The higher levels of self-reactive antibodies, characteristic of preimmune B-cell repertoire, are likely to be a product of nonrandom VH gene family expression and their restricted pairing with three V lambda L-chain genes. These data suggest that a low lambda L-chain expression in normal mice is due, in part, to endogenous selection against lambda L chain in order to restrict self reactivity within the homeostatic threshold.