Interactions and pattern formation in a macroscopic magnetocapillary SALR system of mermaid cereal.

When particles are deposited at a fluid interface they tend to aggregate by capillary attraction to minimize the overall potential energy of the system. In this work, we embed floating millimetric disks with permanent magnets to introduce a competing repulsion effect and study their pattern formation in equilibrium. The pairwise energy landscape of two disks is described by a short-range attraction and long-range repulsion (SALR) interaction potential, previously documented in a number of microscopic condensed matter systems. Such competing interactions enable a variety of pairwise equilibrium states, including the possibility of a local minimum energy corresponding to a finite disk spacing. Two-dimensional (2D) experiments and simulations in confined geometries demonstrate that as the areal packing fraction is increased, the dilute repulsion-dominated lattice state becomes unstable to the spontaneous formation of localized clusters, which eventually merge into a system-spanning striped pattern. Finally, we demonstrate that the equilibrium pattern can be externally manipulated by the application of a supplemental vertical magnetic force that remotely enhances the effective capillary attraction.

The COVID-19 ambulance response assessment (CARA) study: a national survey of ambulance service healthcare professionals' preparedness and response to the COVID-19 pandemic.

Background: The COVID-19 pandemic placed significant demand on the NHS, including ambulance services, but it is unclear how this affected ambulance service staff and paramedics in other clinical settings (e.g. urgent and primary care, armed services, prisons). This study aimed to measure the self-perceived preparedness and impact of the first wave of the pandemic on paramedics' psychological stress and perceived ability to deliver care. Methods: Ambulance clinicians and paramedics working in other healthcare settings were invited to participate in a three-phase sequential online survey during the acceleration (April 2020), peak (May 2020) and deceleration (September/October 2020) phases of the first wave of COVID-19 in the United Kingdom. Recruitment used social media, Trust internal bulletins and the College of Paramedics' communication channels, employing a convenience sampling strategy. Data were collected using purposively developed open- and closed-ended questions and the validated general health questionnaire-12 (GHQ-12). Data were analysed using multi-level linear and logistic regression models. Results: Phase 1 recruited 3717 participants, reducing to 2709 (73%) by phase 2 and 2159 (58%) by phase 3. Participants were mostly male (58%, n = 2148) and registered paramedics (n = 1992, 54%). Mean (standard deviation) GHQ-12 scores were 16.5 (5.2) during phase 1, reducing to 15.2 (6.7) by phase 3. A total of 84% of participants (n = 3112) had a GHQ-12 score ≥ 12 during the first phase, indicating psychological distress. Participants that had higher GHQ-12 scores were feeling unprepared for the pandemic, and reported a lack of confidence in using personal protective equipment and managing cardiac arrests in confirmed or suspected COVID-19 patients. Conclusions: Most participants reported psychological distress, the reasons for which are multi-factorial. Ambulance managers need to be aware of the risks to staff mental health and take action to mitigate these, to support staff in the delivery of unscheduled, emergency and urgent care under these additional pressures.

Interventional management of malignant bone tumours.

In the last few decades, interventional radiology (IR) has significantly increased its role in the management of bone tumours including bone metastases (BM) that represent the most common type of tumour involving the bone. The current IR management of BM is based on the 'palliative-curative' paradigm and relies on the use of consolidative (i.e. osteplasty, osteosynthesis) and/or ablation (i.e. cryoablation, radiofrequency ablation, electrochemotherapy) techniques. The present narrative review will overview the current role of IR for the management of BM.

Development and implementation of a simple and rapid extraction-free saliva SARS-CoV-2 RT-LAMP workflow for workplace surveillance.

Effective management of the COVID-19 pandemic requires widespread and frequent testing of the population for SARS-CoV-2 infection. Saliva has emerged as an attractive alternative to nasopharyngeal samples for surveillance testing as it does not require specialized personnel or materials for its collection and can be easily provided by the patient. We have developed a simple, fast, and sensitive saliva-based testing workflow that requires minimal sample treatment and equipment. After sample inactivation, RNA is quickly released and stabilized in an optimized buffer, followed by reverse transcription loop-mediated isothermal amplification (RT-LAMP) and detection of positive samples using a colorimetric and/or fluorescent readout. The workflow was optimized using 1,670 negative samples collected from 172 different individuals over the course of 6 months. Each sample was spiked with 50 copies/µL of inactivated SARS-CoV-2 virus to monitor the efficiency of viral detection. Using pre-defined clinical samples, the test was determined to be 100% specific and 97% sensitive, with a limit of detection of 39 copies/mL. The method was successfully implemented in a CLIA laboratory setting for workplace surveillance and reporting. From April 2021-February 2022, more than 30,000 self-collected samples from 755 individuals were tested and 85 employees tested positive mainly during December and January, consistent with high infection rates in Massachusetts and nationwide.

Patient satisfaction with telephone consultations in cardiology outpatients during the COVID-19 pandemic.

The COVID-19 pandemic required a radical change in healthcare delivery methods, including the remote delivery of many outpatient services. We aimed to understand patient satisfaction with telephone consultations. Patients who had undergone a cardiology telephone consultation between 24 February and 19 July 2021 were asked to complete a survey. The survey assessed their satisfaction with the consultation and their preference between remote and face-to-face consultation. The 56 responses demonstrated high levels of satisfaction with 56% agreeing they were "completely satisfied" with the consultation compared with 5% who disagreed. However, 63% would have preferred a face-to-face appointment compared with 22% preferring a telephone consultation. No patterns were observed that might help to guide who should be offered the different modalities of consultation; to maximise patient satisfaction a flexible and individualised approach is likely to be required.

A survey of ambulance clinicians' perceptions of recording and communicating patient information electronically.

OBJECTIVE: Ambulance services are evolving from use of paper-based recording of patient information to electronic platforms and the impact of this change has yet to be fully explored. The aim of this study is to explore how the introduction of a system permitting electronic information capture and its subsequent sharing were perceived by the ambulance clinicians using it. METHODS: An online questionnaire was designed based upon the technology acceptance model and distributed throughout one ambulance service in the south east of England. Closed-ended questions with Likert scales were used to collect data from patient-facing staff who use an online community falls and diabetic referral platform or an electronic messaging system to update GPs following a patient encounter. RESULTS: There were 273 responses from ambulance clinicians. Most participants agreed that they used tablet computers and smartphones to make their life easier (85% and 86%, respectively). Most participants felt that referring patients to a community falls or diabetic team electronically was an efficient use of their time (81% and 81%, respectively) and many believed that these systems improved the communication of confidential patient information. GP summaries were perceived as increasing time spent on scene but most participants (89%) believed they enabled collaborative working. Overall, collecting and sharing patient information electronically was perceived by most participants as beneficial to their practice. CONCLUSION: In this study, the ability to electronically refer patients to community services and share patient encounters with the GP was predominantly perceived as both safe for patients and an effective use of the participants' clinical time. However, there is often still a need to communicate to GPs in real time, demonstrating that technology could complement, rather than replace, how clinicians communicate.

How do Self-Assembling Antimicrobial Lipopeptides Kill Bacteria?

Antimicrobial peptides are promising alternatives to traditional antibiotics. A group of self-assembling lipopeptides was formed by attaching an acyl chain to the N-terminus of α-helix-forming peptides with the sequence Cx-G(IIKK)yI-NH2 (CxGy, x = 4-12 and y = 2). CxGy self-assemble into nanofibers above their critical aggregation concentrations (CACs). With increasing x, the CACs decrease and the hydrophobic interactions increase, promoting secondary structure transitions within the nanofibers. Antimicrobial activity, determined by the minimum inhibition concentration (MIC), also decreases with increasing x, but the MICs are significantly smaller than the CACs, suggesting effective bacterial membrane-disrupting power. Unlike conventional antibiotics, both C8G2 and C12G2 can kill Staphylococcus aureus and Escherichia coli after only minutes of exposure under the concentrations studied. C12G2 nanofibers have considerably faster killing dynamics and lower cytotoxicity than their nonaggregated monomers. Antimicrobial activity of peptide aggregates has, to date, been underexploited, and it is found to be a very promising mechanism for peptide design. Detailed evidence for the molecular mechanisms involved is provided, based on superresolution fluorescence microscopy, solid-state nuclear magnetic resonance, atomic force microscopy, neutron scattering/reflectivity, circular dichroism, and Brewster angle microscopy.

Ready-to-use nanopore platform for the detection of any DNA/RNA oligo at attomole range using an Osmium tagged complementary probe.

Nanopores can serve as single molecule sensors. We exploited the MinION, a portable nanopore device from Oxford Nanopore Technologies, and repurposed it to detect any DNA/RNA oligo (target) in a complex mixture by conducting voltage-driven ion-channel measurements. The detection and quantitation of the target is enabled by the use of a unique complementary probe. Using a validated labeling technology, probes are tagged with a bulky Osmium tag (Osmium tetroxide 2,2'-bipyridine), in a way that preserves strong hybridization between probe and target. Intact oligos traverse the MinION's nanopore relatively quickly compared to the device's acquisition rate, and exhibit count of events comparable to the baseline. Counts are reported by a publicly available software, OsBp_detect. Due to the presence of the bulky Osmium tag, probes traverse more slowly, produce multiple counts over the baseline, and are even detected at single digit attomole (amole) range. In the presence of the target the probe is "silenced". Silencing is attributed to a 1:1 double stranded (ds) complex that does not fit and cannot traverse this nanopore. This ready-to-use platform can be tailored as a diagnostic test to meet the requirements for point-of-care cell-free tumor DNA (ctDNA) and microRNA (miRNA) detection and quantitation in body fluids.

A catalogue of biochemically diverse CRISPR-Cas9 orthologs.

Bacterial Cas9 nucleases from type II CRISPR-Cas antiviral defence systems have been repurposed as genome editing tools. Although these proteins are found in many microbes, only a handful of variants are used for these applications. Here, we use bioinformatic and biochemical analyses to explore this largely uncharacterized diversity. We apply cell-free biochemical screens to assess the protospacer adjacent motif (PAM) and guide RNA (gRNA) requirements of 79 Cas9 proteins, thus identifying at least 7 distinct gRNA classes and 50 different PAM sequence requirements. PAM recognition spans the entire spectrum of T-, A-, C-, and G-rich nucleotides, from single nucleotide recognition to sequence strings longer than 4 nucleotides. Characterization of a subset of Cas9 orthologs using purified components reveals additional biochemical diversity, including both narrow and broad ranges of temperature dependence, staggered-end DNA target cleavage, and a requirement for long stretches of homology between gRNA and DNA target. Our results expand the available toolset of RNA-programmable CRISPR-associated nucleases.

Agonists of Orally Expressed TRP Channels Stimulate Salivary Secretion and Modify the Salivary Proteome.

Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva. Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared with unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative MS method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and nonsalivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.

Differences in the Natural Enamel Surface and Acquired Enamel Pellicle following Exposure to Citric or Hydrochloric Acid.

OBJECTIVES: The aim of this study was to investigate variations in the interaction between enamel, that is, the acquired enamel pellicle (AEP) and citric or hydrochloric acid. MATERIALS AND METHODS: A 24-h AEP was formed on natural enamel specimens (n = 40) from pooled whole mouth human saliva. Samples were randomly allocated to citric (0.3%, pH 3.2) or hydrochloric (HCl) acid (0.01 M, pH 2.38) exposure for 30 or 300 s. The total protein concentration (TPC), and phosphorous and calcium concentrations of the pellicle were determined before and after acid exposure, and again after re-immersion in saliva. Surface roughness and tandem scanning confocal microscopy imaging were used to assess enamel changes. RESULTS: After 300 s of citric acid exposure, the mean ± SD TPC reduced from 5.1 ± 1.1 to 3.5 ± 1.1 mg/mL (p < 0.05). In contrast, after 300 s of HCl exposure, the mean TPC did not reduce significantly from baseline (6.6 ± 1.1 to 5.7 ± 0.7 mg/mL) but was significantly reduced in the reformed pellicle to 4.9 ± 1.2 mg/mL (p < 0.001). This reduction occurred after significant release of calcium and phosphorous from the enamel surface (p < 0.001). Thirty seconds of exposure to either acid had no obvious effect on the AEP. The surface roughness of the enamel decreased after acid exposure but no differences between groups was observed. CONCLUSIONS: These findings indicate that citric acid interacted with proteins in the AEP upon contact, offering enamel protection. In contrast, HCl appeared to bypass the pellicle, and reduced protein was observed only after changes in the enamel chemical composition.

Therminator DNA Polymerase: Modified Nucleotides and Unnatural Substrates.

A variant of 9°N DNA polymerase [Genbank ID (AAA88769.1)] with three mutations (D141A, E143A, A485L) and commercialized under the name "Therminator DNA polymerase" has the ability to incorporate a variety of modified nucleotide classes. This Review focuses on how Therminator DNA Polymerase has enabled new technologies in synthetic biology and DNA sequencing. In addition, we discuss mechanisms for increased modified nucleotide incorporation.

Cash on delivery: Results of a randomized experiment to promote maternal health care in Kenya.

We conducted a randomized controlled experiment to test whether vouchers, cash transfers, and SMS messages were effective in boosting facility delivery rates among poor, pregnant women in rural Kenya. We find a strong effect of the full vouchers and the conditional cash transfers: 48% of women with access to both interventions delivered in a health facility, while only 36% of those with neither did. Amongst women who did not receive a cash transfer, we find that a small copayment dramatically reduced voucher effectiveness, suggesting a discontinuous impact of cost-sharing on the demand for health services. Both the unconditional cash transfer and the text messages had limited effect on the use of health services. Finally, we also find no evidence that a government policy to eliminate user fees increased demand for maternal health services.

A retrospective review of patients with significant traumatic brain injury transported by emergency medical services within the south east of England.

INTRODUCTION: Traumatic brain injury (TBI) will be a leading cause of death and disability within the Western world by 2020. Currently, 80% of all TBI patients in England are transported to hospital by an ambulance service. The aim of this retrospective study is to compare TBI patients transported to a major trauma centre (MTC) against those transported to a trauma unit (TU). METHOD: All patients with a primary injury of TBI who were transported to hospital by South East Coast Ambulance Service NHS Foundation Trust (SECAmb) from 1 January 2016 to 31 December 2016 and entered into the Trauma Audit & Research Network (TARN) registry were reviewed. Patients were stratified by hospital designation (MTC or TU). Severity of TBI was categorised using the patients' pre-hospital Glasgow Coma Scale (GCS) and Abbreviated Injury Score (AIS) Head. The outcomes of interest were 30-day mortality and Glasgow Outcome Score (GOS) at discharge. RESULTS: Between 1 January and 31 December 2016, 549 TBI patients were identified in the TARN database as being transported by SECAmb to either an MTC or a TU. The majority of patients were transported to a TU (77.96%), and the median age of the TU cohort was older than the MTC group (TU 82.15 IQR 16.73 vs. MTC 62.1 IQR 42.6). The median Injury Severity Score (ISS) was greater in the MTC cohort (22 IQR 10 vs. 17 IQR 9), where falls from height and road traffic collisions (RTCs) contributed to 50.51% of all injuries. Within the TU cohort, falls from less than 2 metres (standing height) were the main mechanism of injury (MOI) (77.62%). The median length of hospital stay (LOS) was longer in the MTC cohort compared to the TU cohort (10 IQR 13.25 vs. 8 IQR 14). CONCLUSION: The high proportion of mild TBI and absence of reliable triage guidelines make it difficult for ambulance clinicians to identify patients who will benefit from transport to an MTC. Future research should focus on how TBI triage influences outcomes and how ambulance services can better identify patients with a TBI and who would benefit from specialist care.

Efficacy of the cardiac septal occluder in the treatment of post-bariatric surgery leaks and fistulas.

BACKGROUND: Endoscopy has evolved to become first-line therapy for the treatment of post-bariatric leaks; however, many sessions are often required with variable success rates. Due to these limitations, the use of the cardiac septal defect occluder (CSDO) has recently been reported in this population. METHODS: The study population was a multicenter retrospective series of patients with post-bariatric surgical leaks who underwent treatment with CSDO placement. Data on the type of surgery, previous treatment details, fistula dimensions, success rate, and adverse events were collected. Leaks were grouped according to the International Sleeve Gastrectomy Expert Panel Consensus. Outcomes included technical and clinical success and safety of the CSDO. Regression analysis was performed to determine the predictors of response. RESULTS: Forty-three patients with leaks were included (31 sleeve gastrectomy and 12 Roux-en-Y gastric bypass). They were divided into acute (n = 3), early (n = 5), late (n = 23), and chronic (n = 12). Forty patients had failed previous endoscopic treatment and 3 patients had CSDO as the primary treatment. Median follow-up was 34 weeks. Technical success was achieved in all patients and clinical success in 39 patients (90.7%). All chronic, late, and early leaks were successfully closed, except one undrained late leak. The 5 patients with early leaks had an initial satisfactory response, but within 30 days, drainage recurred. The CSDOs were removed and replaced with larger-diameter devices leading to permanent defect closure. Acute leaks were not successfully closed in all 3 patients. Regression analysis showed that chronicity and previous treatment were associated with fistula closure; success rates for late/chronic leaks versus acute/early leaks were 97.1% and 62.5%, respectively (P = .0023). CONCLUSION: This observational study found that the CSDO had a high efficacy rate in patients with non-acute leaks, with no adverse events. All early, late, and chronic leaks were successfully closed, except for one undrained late leak. However, early leaks required a second placement of a larger CSDO in all cases. These results suggest that the CSDO should be considered for non-acute fistula and that traditional closure methods are likely preferred in the acute and early settings.

Improving out-of-hours surgical patient care.

PURPOSE: The Royal College of Surgeons recognises patient handover as the point at which patients are collectively at their most vulnerable. Concerns were raised in a London teaching hospital surgical department regarding an unstructured handover system, poor access to relevant clinical information, and inadequate weekend staffing. A quality improvement programme was designed and implemented to respond to these concerns and improve patient safety. The paper aims to discuss these issues. DESIGN/METHODOLOGY/APPROACH: A structured questionnaire was distributed to staff and results used to construct a diagram outlining the main factors influencing weekend patient safety. This framework was used to design changes, including a new electronic handover tool, regular handover meetings and additional weekend staff. Regular staff training was provided, and success was assessed in a continuous audit cycle with the results fed back to team leaders. FINDINGS: Over a three-month period, the handover meeting recorded an attendance rate consistently above 80 per cent. The electronic handover entries were scored according to seven criteria (correct layout; key information, i.e.: patient location, clinical priority, active issues, resuscitation status, test results and weekend plan), averaging between 42.2 and 92.9 per cent, with progressive improvement seen over the assessment period. Weekend staffing was increased by 50 per cent, allowing a dedicated team to care for stable inpatients and to oversee discharges. ORIGINALITY/VALUE: This improvement programme delivered lasting and significant change in response to staff concerns. It resulted in a more structured and reliable weekend system and established key mechanisms for dynamic performance feedback.