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'.

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.

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.

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.

Perinatal outcome after ultrasound diagnosis of anhydramnios at term.

The aim was to assess the maternal and fetal outcome in women who had labour induced for anhydramnios after 37 completed weeks of gestation. A retrospective study was conducted at the Rotunda Hospital from 1 January 2003 to 31 December 2007. All women with anhydramnios at term were identified from a review of ViewPoint® (computer software for antenatal scans performed), hospital data and the labour ward register. All women with a history of previous lower segment caesarean section (LSCS), current significant medical illness such as diabetes, hypertension, pre-eclampsia or ruptured membranes were excluded because the aim of the study was to focus specifically on low risk pregnancies with an incidental diagnosis of anhydramnios after 37 weeks' gestation. The maternal and fetal outcome parameters reviewed included: maternal age, parity, gestation, method of induction, mode of delivery, Apgar score and the requirement for obstetric or neonatal intervention. This study showed that anhydramnios is associated with a 56.6% LSCS rate in primigravida and a 19.0% LSCS rate in multigravida. Our study did not show any significant neonatal morbidity and there were no cases of mortality.

Ponderal index (PI) vs birth weight centiles in the low-risk primigravid population: which is the better predictor of fetal wellbeing?

Our objective was to compare Ponderal index (PI) with birth weight centiles as predictors of perinatal morbidity and to determine which best reflects the presence of placental disease. We prospectively recruited 1,011 low-risk primigravidas and calculated PI and birth weight centiles following delivery. Perinatal morbidity was defined as: pre-term birth (PTB); fetal acidosis; an Apgar score <7 at 5 min or neonatal resuscitation. Placental disease was defined as chronic uteroplacental insufficiency (CUPI); villous dysmaturity; infection or vascular pathology. Ponderal index was statistically reduced (25.33 vs 27.79 p =0.001) and the incidence of infant birth weight <9th centile was statistically higher (11.1% vs 5.1%; p =0.004) in cases with PTB and in CUPI (26.23 vs 27.84; p =0.001 and 28.2.1% vs 10.4%; p =0.002). Both PI and infant birth weight centile <9th centile for gestational age correlate with PTB, however overall, both are poor predictors of neonatal and placental disease.

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.

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.

Amazon River enhances diazotrophy and carbon sequestration in the tropical North Atlantic Ocean.

The fresh water discharged by large rivers such as the Amazon is transported hundreds to thousands of kilometers away from the coast by surface plumes. The nutrients delivered by these river plumes contribute to enhanced primary production in the ocean, and the sinking flux of this new production results in carbon sequestration. Here, we report that the Amazon River plume supports N(2) fixation far from the mouth and provides important pathways for sequestration of atmospheric CO(2) in the western tropical North Atlantic (WTNA). We calculate that the sinking of carbon fixed by diazotrophs in the plume sequesters 1.7 Tmol of C annually, in addition to the sequestration of 0.6 Tmol of C yr(-1) of the new production supported by NO(3) delivered by the river. These processes revise our current understanding that the tropical North Atlantic is a source of 2.5 Tmol of C to the atmosphere [Mikaloff-Fletcher SE, et al. (2007) Inverse estimates of the oceanic sources and sinks of natural CO(2) and the implied oceanic carbon transport. Global Biogeochem Cycles 21, doi:10.1029/2006GB002751]. The enhancement of N(2) fixation and consequent C sequestration by tropical rivers appears to be a global phenomenon that is likely to be influenced by anthropogenic activity and climate change.

The relationship between body mass index and mid-arm circumference in a pregnant population.

Our objective was to correlate body mass index (BMI) with mid-arm circumference (MAC) and also to ascertain whether maternal BMI could be calculated from MAC at booking. We approached all Caucasian women who met the inclusion criteria attending the University College Hospital, London between 1 April 1996 and 30 June 1997 and the Rotunda Hospital, Dublin, Ireland between 15 April 2003 and 19 May 2004. A total of 2,912 women agreed to participate in the research. The participants' maternal height and weight were measured. Their BMI was calculated using the formula: BMI = weight (kg) ÷ height (m(2)). The MAC was measured in cm. Statistical analysis was performed using SPSS for Windows version 11 with p < 0.05 as significant. We found that BMI is directly correlated with MAC (r = 0.836) and estimates of BMI may be calculated from the simple equation BMI = MAC ± 2. Alternatively, a MAC of ≥ 27 cm allowed for a detection rate for overweight patients of 75%, with a false positive rate of 15%.

Successful fetoscopic laser coagulation for twin-to-twin transfusion syndrome under local anaesthesia.

A review of the efficacy and outcome of fifteen fetoscopic laser ablations under local anaesthesia for twin to twin transfusion syndrome (TTTS) in the National Maternity Hospital Dublin was undertaken. The mean gestation at laser was 19.7 weeks (range 16-25 weeks) with a mean gestation at delivery of 29.1 weeks (range 20-35 weeks). The overall liveborn birth rate was 79% (22 infants) and one pregnancy was still ongoing. There were four neonatal deaths secondary to complications of prematurity. The surviving eighteen infants (64%) undergo regular paediatric review. The procedure was performed successfully in all cases with local anaesthesia. In no case was there maternal discomfort that warranted the procedure to be abandoned and good visual access of the vascular anastamoses was obtained in all cases. Local anaesthesia therefore offers a safe effective anaesthetic option for fetoscopic laser coagulation in monochorionic pregnancies complicated by TTTS.

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.

Associative learning in egglaying site selection by apple maggot flies.

Evidence is presented demonstrating that associative learning during oviposition in Crataegus or apple hosts can significantly influence the propensity of apple maggot flies to accept or reject these hosts in future encounters. The data suggest that within resource patches of a given host type there may be an enhancement of foraging efficiency.

Natural history of apparently isolated severe fetal ventriculomegaly: perinatal survival and neurodevelopmental outcome.

OBJECTIVE: To review the prenatal diagnosis of apparently isolated severe ventriculomegaly (SVM) in a tertiary referral fetal medicine unit and report on perinatal and neurodevelopmental outcomes. METHODS: All cases of isolated SVM referred to Fetal Medicine at the NMH between 2000 and 2008 were identified. Outcome information was obtained from detailed telephone interviews with parents and paediatric records and histopathology in cases of stillborn fetuses. RESULTS: Thirty-six cases of SVM were referred, out of which 19 were diagnosed with 'apparently' isolated SVM. Macrocrania was present in 88% at 36 weeks (mean HC 439 mm). Cephalocentesis was performed in six cases with poor prognosis. All resulted in perinatal loss. The neurodevelopmental outcome of survivors with isolated SVM (ten live-born survivors) showed major neurological morbidity in 50% (5/10) of the cases, mild morbidity in 40% (4/10) and a normal outcome in only one case. CONCLUSION: Isolated SVM had a very poor perinatal outcome with neurological and physical disability in the overwhelming majority. Only one case of the 17 (6%) diagnosed initially with 'apparently' isolated SVM was born alive without handicap. Information from our series may aid couples in decision making about pregnancy interruption and the difficult decision of prenatal or intrapartum cephalocentesis.

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.