Audit of Ireland's first manual vacuum aspiration service.

INTRODUCTION: Manual vacuum aspiration (MVA) is a safe and effective alternative option for the management of first-trimester miscarriage, termination of pregnancy, or retained pregnancy tissue. Ireland's first MVA clinic was set up in the Rotunda Hospital in April 2020. OBJECTIVE: To identify the number of women who have undergone MVA since establishing our service, to assess the efficacy and safety of MVA in that service, and to develop local Irish studies that further support the safety of MVA, adding to the international body of evidence. METHODS: With the approval and assistance of the Clinical Audit Committee, we obtained a log of all patients who underwent MVA in the first 18 months of the service. We performed a retrospective electronic chart review using Maternal and Newborn Clinical Management System. We collected the data and preformed a descriptive analysis. RESULTS: In total, 86 women underwent MVA, 85 (98.8%) of which were successfully completed. There were no immediate procedural complications, inter-hospital transfers, or emergency electric vacuum aspiration (EVA) required. We obtained an incomplete evacuation rate of 4.7% (n = 4). CONCLUSION: We have demonstrated that the MVA service in the Rotunda Hospital is a safe, effective management option with advantages for both the patient and the healthcare system. We recommend consideration for provision of funding and resources to enable expansion of this service nationally in order to give women greater autonomy of choice in the management of early pregnancy complications and termination of pregnancy.

3D-printing and cylinder buckling: challenges and opportunities.

Cylinder buckling is notoriously sensitive to small geometric imperfections. This is an underlying motivation for the use of knock-down factors in the design process, especially in circumstances in which minimum weight is a key design goal, an approach well-established at NASA, for example. Not only does this provide challenges in the practical design of this commonly occurring structural load-bearing configuration, but also in the carefully controlled laboratory setting. The recent development of 3D-printing (additive manufacturing) provides an appealing experimental platform for conducting relatively high-fidelity experiments on the buckling of cylinders. However, in addition to geometric precision, there are a number of shortcomings with this approach, and this article seeks to describe the challenges and opportunities associated with the use of 3D-printing in cylinder buckling in general, and probing the robustness of equilibrium configurations in particular. This article is part of the theme issue 'Probing and dynamics of shock sensitive shells'.

Decreasing surface albedo signifies a growing importance of clouds for Greenland Ice Sheet meltwater production.

Clouds regulate the Greenland Ice Sheet's surface energy balance through the competing effects of shortwave radiation shading and longwave radiation trapping. However, the relative importance of these effects within Greenland's narrow ablation zone, where nearly all meltwater runoff is produced, remains poorly quantified. Here we use machine learning to merge MODIS, CloudSat, and CALIPSO satellite observations to produce a high-resolution cloud radiative effect product. For the period 2003-2020, we find that a 1% change in cloudiness has little effect (±0.16 W m-2) on summer net radiative fluxes in the ablation zone because the warming and cooling effects of clouds compensate. However, by 2100 (SSP5-8.5 scenario), radiative fluxes in the ablation zone will become more than twice as sensitive (±0.39 W m-2) to changes in cloudiness due to reduced surface albedo. Accurate representation of clouds will therefore become increasingly important for forecasting the Greenland Ice Sheet's contribution to global sea-level rise.

Early pregnancy teaching and training amongst obstetric trainees in a tertiary maternity hospital.

Proficiency in early pregnancy assessment and management is a core component of Basic Speciality Training (BST) in Obstetrics & Gynaecology. Performance and interpretation of early pregnancy ultrasound is not formalised in Ireland, resulting in variation in exposure and experience amongst trainees. We aimed to improve trainee's knowledge and confidence in early pregnancy ultrasound. This was though a multimodel teaching program of didactic lectures, tutorials, and case-based discussions. Additionally, we organised structed assessment tests over a six-week period with a repeat revision of teaching to allow all participants attendance. All teaching was provided with facilities already available in our institution. We assessed knowledge and confidence by an anonymised survey comprising both quantitative and qualitative components pre and post training completion. We showed an improvement in knowledge, a non-significant increase was noted in mean test score in multiple choice questions relating to early pregnancy from 78.8% to 83.5% post study completion. Trainees were noted to report an increase in training during the duration of the study with 70% reporting have received little training prior to the study dropping to 13% at the end. Increased exposure to both witnessed and performed transabdominal and transvaginal ultrasound and training on the interpretation of early pregnancy ultrasound was noted. Among trainees 62% reported no formalised training in interpreting early pregnancy ultrasound at commencement reducing to 13% post study (p = 0.04). Improved confidence although non-significant was also reported among trainees. Our study demonstrates that a low-cost multimodel teaching program over a short time frame can improve knowledge, confidence and interpretation in early pregnancy ultrasound. This simple model can be easily reproduced in other institutions. As this was a pilot study, we would envision expanding it across further sites to assess its effectiveness.

Womens experience of Manual Vacuum Aspiration: An Irish perspective.

OBJECTIVE: Manual Vacuum Aspiration (MVA) is a well-established management option for early pregnancy loss or early termination of pregnancy. MVA is performed as out-patient surgical procedure using local anaesthetic whereby aspiration of uterine contents is achieved through use of a hand-held negative pressure syringe. Ireland's first MVA service was established at the Rotunda Hospital Dublin in April 2020,. The purpose of this study was to gather feedback from women who had undergone MVA in the unit. STUDY DESIGN: Prospective mixed methods study of women attending for uterine aspiration under local anaesthetic from July to October 2020 in the unit. Consenting women were contacted one week following MVA via telephone. The survey conducted consisted of structured closed questions along with open-ended questions, to assess womens satisfaction in relation to all aspects of the MVA service. RESULTS: Nineteen women took part in the study, a response rate of 86.4%. Participants reported feeling well informed prior to attending for MVA. Prior to the procedure, pain expectation scores were high but actual reported pain scores were much lower. Although some participants did find MVA uncomfortable, the fact the procedure was very quick and the side effects so minimal generally negated this. The location and set up of the clinic scored highly among participants as did the staff of the clinic. Overall satisfaction with the MVA service was high with 84.2% of participants reporting they would opt again for MVA in the future. CONCLUSIONS: Women living in Ireland are interested and agreeable with having Manual Vacuum Aspiration as an available option for management of early pregnancy complications. Consideration should be given to expansion of MVA services nationally.

Mobile Stroke Units Facilitate Prehospital Management of Intracerebral Hemorrhage.

Background and Purpose: Mobile stroke units (MSUs) improve reperfusion therapy times in acute ischemic stroke (AIS). However, prehospital management options for intracerebral hemorrhage (ICH) are less established. We describe the initial Melbourne MSU experience in ICH. Methods: Consecutive patients with ICH and AIS treated by the Melbourne MSU were included. We describe demographics, proportions of patients receiving specific therapies, and bypass to comprehensive/neurosurgical centers. We also compare operational time metrics between patients with MSU-ICH and MSU-AIS. Results: During a 2-year period, the Melbourne MSU managed 49 patients with ICH, mean (SD) age 74 (12) years, median (interquartile range) National Institutes of Health Stroke Scale 17 (12­20). Intravenous antihypertensives were the commonest treatment provided (46.9%). Bypass of a primary center to a comprehensive center with neurosurgical expertise occurred in 32.7% of patients with MSU-ICH compared with 20.5% of patients with MSU-AIS. Compared with patients with MSU-AIS, patients with MSU-ICH had faster onset-to-emergency-call, and onset-to-scene-arrival times at the median and 75th percentiles. Conclusions: MSUs can facilitate ultra-early ICH diagnosis, management, and triage.

Impact of Introduction of a Clinical Pathway for the Management of Pyelonephritis on Obstetric Patients: a Quality Improvement Project

Aim To determine whether the introduction of a clinical pathway for the treatment of pyelonephritis in obstetric patients would improve outcomes. Methods This was a retrospective study conducted in a maternity hospital using quantitative analysis methods. Patients who met laboratory and clinical criteria for pyelonephritis during data collection were included. Results The study included analysis of 23 patients pre-intervention and 19 post-intervention. Baseline and patient characteristics were similar for both groups. A statistically significant difference was seen in 3 of 7 outcome measures. Increased use of gentamicin (13% Vs 52% p=0.006), Increased number of renal ultrasounds (17% Vs 47%, p=0.04) and increased use of prophylaxis (21% Vs 68%, p=0.003). The proportion of patients receiving ≥ 10 days of IV antimicrobials decreased from 48% to 21% post-intervention (p=0.07). Discussion This study has shown that the introduction of a pathway for the treatment of pyelonephritis in pregnancy had a positive impact on several important clinical outcomes.

Greenland Ice Sheet surface melt amplified by snowline migration and bare ice exposure.

Greenland Ice Sheet mass loss has recently increased because of enhanced surface melt and runoff. Since melt is critically modulated by surface albedo, understanding the processes and feedbacks that alter albedo is a prerequisite for accurately forecasting mass loss. Using satellite imagery, we demonstrate the importance of Greenland's seasonally fluctuating snowline, which reduces ice sheet albedo and enhances melt by exposing dark bare ice. From 2001 to 2017, this process drove 53% of net shortwave radiation variability in the ablation zone and amplified ice sheet melt five times more than hydrological and biological processes that darken bare ice itself. In a warmer climate, snowline fluctuations will exert an even greater control on melt due to flatter ice sheet topography at higher elevations. Current climate models, however, inaccurately predict snowline elevations during high melt years, portending an unforeseen uncertainty in forecasts of Greenland's runoff contribution to global sea level rise.

Treatment of glioblastoma using multicomponent silica nanoparticles.

Glioblastomas (GBMs) remain highly lethal. This partially stems from the presence of brain tumor initiating cells (BTICs), a highly plastic cellular subpopulation that is resistant to current therapies. In addition to resistance, the blood-brain barrier limits the penetration of most drugs into GBMs. To effectively deliver a BTIC-specific inhibitor to brain tumors, we developed a multicomponent nanoparticle, termed Fe@MSN, which contains a mesoporous silica shell and an iron oxide core. Fibronectin-targeting ligands directed the nanoparticle to the near-perivascular areas of GBM. After Fe@MSN particles deposited in the tumor, an external low-power radiofrequency (RF) field triggered rapid drug release due to mechanical tumbling of the particle resulting in penetration of high amounts of drug across the blood-brain tumor interface and widespread drug delivery into the GBM. We loaded the nanoparticle with the drug 1400W, which is a potent inhibitor of the inducible nitric oxide synthase (iNOS). It has been shown that iNOS is preferentially expressed in BTICs and is required for their maintenance. Using the 1400W-loaded Fe@MSN and RF-triggered release, in vivo studies indicated that the treatment disrupted the BTIC population in hypoxic niches, suppressed tumor growth and significantly increased survival in BTIC-derived GBM xenografts.

Interreader agreement of radiographic left atrial enlargement in dogs and comparison to echocardiographic left atrial assessment.

INTRODUCTION: Assessing left atrial (LA) size is an integral part of the cardiac evaluation in dogs. Left atrial size is routinely evaluated by thoracic radiographs or echocardiography. OBJECTIVES: The objectives of the study were to assess agreement of subjective radiographic left atrial enlargement (LAE) between readers, to compare subjective radiographic LAE with echocardiography, and to assess the accuracy and reliability of commonly used Roentgen signs for LAE. ANIMALS: One hundred one dogs with thoracic radiographs and echocardiography performed on the same day at a veterinary teaching hospital were retrospectively reviewed. METHODS: Thoracic radiographs were reviewed by two cardiologists, two radiologists, and two small animal rotating interns. Radiographs were evaluated for the subjective presence and severity of LAE and for seven Roentgen signs. Echocardiographic LA size was evaluated objectively by the left atrial-to-aortic root ratio and LA volume indexed to body weight. Interreader agreement of radiographic LAE evaluation and agreement between radiographic LAE assessment and echocardiographic LAE were assessed by linearly weighted kappa and intraclass correlation coefficient. RESULTS: Interreader agreement for the presence and degree of radiographic LAE ranged from moderate to substantial. The agreement between subjective radiographic LAE and echocardiographic LAE was moderate. Single Roentgen signs had poor to fair correlation with echocardiographic LAE. CONCLUSIONS: The present study found that interreader agreement for radiographic classification of LAE was substantial among specialists and moderate for all readers. Subjective, global assessment of radiographic LAE is better than using any single Roentgen sign.

Advances in clinical NK cell studies: Donor selection, manufacturing and quality control.

Natural killer (NK) cells are increasingly used in clinical studies in order to treat patients with various malignancies. The following review summarizes platform lectures and 2013-2015 consortium meetings on manufacturing and clinical use of NK cells in Europe and United States. A broad overview of recent pre-clinical and clinical results in NK cell therapies is provided based on unstimulated, cytokine-activated, as well as genetically engineered NK cells using chimeric antigen receptors (CAR). Differences in donor selection, manufacturing and quality control of NK cells for cancer immunotherapies are described and basic recommendations are outlined for harmonization in future NK cell studies.

CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT.

We have recently described a specialized subset of human natural killer (NK) cells with a CD56(dim)CD57(+)NKG2C(+) phenotype that expand specifically in response to cytomegalovirus (CMV) reactivation in hematopoietic cell transplant (HCT) recipients and exhibit properties characteristic of adaptive immunity. We hypothesize that these cells mediate relapse protection and improve post-HCT outcomes. In 674 allogeneic HCT recipients, we found that those who reactivated CMV had lower leukemia relapse (26% (17-35%), P=0.05) and superior disease-free survival (DFS) (55% (45-65%) P=0.04) 1 year after reduced intensity conditioning (RIC) compared with CMV seronegative recipients who experienced higher relapse rates (35% (27-43%)) and lower DFS (46% (38-54%)). This protective effect was independent of age and graft-vs-host disease and was not observed in recipients who received myeloablative regimens. Analysis of the reconstituting NK cells demonstrated that CMV reactivation is associated with both higher frequencies and greater absolute numbers of CD56(dim)CD57(+)NKG2C(+) NK cells, particularly after RIC HCT. Furthermore, expansion of these cells at 6 months posttransplant independently trended toward a lower 2-year relapse risk. Together, our data suggest that the protective effect of CMV reactivation on posttransplant relapse is in part driven by adaptive NK cell responses.

OCEANOGRAPHY. Contrasting futures for ocean and society from different anthropogenic CO2 emissions scenarios.

The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems­and the goods and services they provide­for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend. A reduced emissions scenario­consistent with the Copenhagen Accord's goal of a global temperature increase of less than 2°C­is much more favorable to the ocean but still substantially alters important marine ecosystems and associated goods and services. The management options to address ocean impacts narrow as the ocean warms and acidifies. Consequently, any new climate regime that fails to minimize ocean impacts would be incomplete and inadequate.

Augmentation of diaphyseal fractures of the radius and ulna in toy breed dogs using a free autogenous omental graft and bone plating.

OBJECTIVES: Evaluation of the short-term outcome, duration of bone healing, and complications following bone plate fixation in dogs weighing ≤6 kg, with and without the use of a free autogenous greater omental graft (OG). MATERIALS AND METHODS: A retrospective clinical study reviewed the medical records of 25 dogs of body weight <6 kg with mid to distal diaphyseal fractures of the radius and ulna (29 fractures) treated with open reduction bone plate fixation. Thirteen out of 29 fractures were implanted with an additional 2-3 cm³ OG lateral, cranial, and medial to the fracture site, adjacent to the bone plate. RESULTS: Median time to radiographic healing in OG fractures (n = 11) was 70 days (range 28-98) compared to 106 days (range: 56-144) in non-OG grafted fractures (n = 14). The OG dogs had no major complications; minor complications included oedema, erythema, and mild osteopenia. Six of the eight non-OG dogs for which follow-up could be obtained developed osteopenia necessitating implant removal, four of which re-fractured the radius one to five months after implant removal, with one dog re-fracturing the limb a second time and resulting in amputation. Telephone follow-up of owners of OG dogs (n = 11) three to 15 months (median 10) post-surgery did not identify any signs of lameness or other complications. Owners of the non-OG dogs (n = 8) reported that there were not any signs of lameness six to 48 months (median 36) post-surgery. CLINICAL RELEVANCE: Free autogenous omental grafting of diaphyseal fractures of the radius and ulna was associated with radial and ulnar healing with minimal complications in dogs weighing less than 6 kg.

Characterization of a weakly expressed KIR2DL1 variant reveals a novel upstream promoter that controls KIR expression.

Members of the human KIR (killer cell immunoglobulin-like receptor) class I major histocompatibility complex receptor gene family contain multiple promoters that determine the variegated expression of KIR on natural killer cells. In order to identify novel genetic alterations associated with decreased KIR expression, a group of donors was characterized for KIR gene content, transcripts and protein expression. An individual with a single copy of the KIR2DL1 gene but a very low level of gene expression was identified. The low expression phenotype was associated with a single-nucleotide polymorphism (SNP) that created a binding site for the inhibitory ZEB1 (Zinc finger E-box-binding homeobox 1) transcription factor adjacent to a c-Myc binding site previously implicated in distal promoter activity. Individuals possessing this SNP had a substantial decrease in distal KIR2DL1 transcripts initiating from a novel intermediate promoter located 230 bp upstream of the proximal promoter start site. Surprisingly, there was no decrease in transcription from the KIR2DL1 proximal promoter. Reduced intermediate promoter activity revealed the existence of alternatively spliced KIR2DL1 transcripts containing premature termination codons that initiated from the proximal KIR2DL1 promoter. Altogether, these results indicate that distal transcripts are necessary for KIR2DL1 protein expression and are required for proper processing of sense transcripts from the bidirectional proximal promoter.

Genotype List String: a grammar for describing HLA and KIR genotyping results in a text string.

Knowledge of an individual's human leukocyte antigen (HLA) genotype is essential for modern medical genetics, and is crucial for hematopoietic stem cell and solid-organ transplantation. However, the high levels of polymorphism known for the HLA genes make it difficult to generate an HLA genotype that unambiguously identifies the alleles that are present at a given HLA locus in an individual. For the last 20 years, the histocompatibility and immunogenetics community has recorded this HLA genotyping ambiguity using allele codes developed by the National Marrow Donor Program (NMDP). While these allele codes may have been effective for recording an HLA genotyping result when initially developed, their use today results in increased ambiguity in an HLA genotype, and they are no longer suitable in the era of rapid allele discovery and ultra-high allele polymorphism. Here, we present a text string format capable of fully representing HLA genotyping results. This Genotype List (GL) String format is an extension of a proposed standard for reporting killer-cell immunoglobulin-like receptor (KIR) genotype data that can be applied to any genetic data that use a standard nomenclature for identifying variants. The GL String format uses a hierarchical set of operators to describe the relationships between alleles, lists of possible alleles, phased alleles, genotypes, lists of possible genotypes, and multilocus unphased genotypes, without losing typing information or increasing typing ambiguity. When used in concert with appropriate tools to create, exchange, and parse these strings, we anticipate that GL Strings will replace NMDP allele codes for reporting HLA genotypes.

Circulating pro- and anticoagulant levels in normal and complicated primigravid pregnancies and their relationship to placental pathology.

We aimed to compare the changes in factor VIII:C, antithrombin, protein C, protein S and fibrinogen in a cohort of low-risk primigravida who developed maternal or fetal complications to those who had uncomplicated pregnancies and to correlate these findings with placental pathology. This is a case-control study of 170 cases and 122 controls selected from a prospective cohort of 1,011 low-risk primigravida. Significantly elevated levels of factor VIII:C and significantly decreased levels of antithrombin were seen in women who developed pre-eclampsia (p <0.001), placental infarction (p < 0.001) or had infants with a birth weight < 3rd centile (p < 0.001). Placental villous dysmaturity was significantly associated with raised factor VIII:C (p < 0.001). Women who developed pre-eclampsia showed elevated fibrinogen at 14 weeks (p = 0.03). Significantly higher than normal pregnancy levels of factor VIII:C, in tandem with significantly lower antithrombin levels associated with certain adverse pregnancy outcomes, may be related to underlying placental insufficiency. This is supported by associated placental findings.