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Levamisole is an increasingly common cutting agent used with cocaine. Both cocaine and levamisole can have local and systemic effects on patients.
A retrospective case series was conducted of patients with a cocaine-induced midline destructive lesion or levamisole-induced vasculitis, who presented to a Dundee hospital or the practice of a single surgeon in Paisley, from April 2016 to April 2019. A literature review on the topic was also carried out.
Nine patients from the two centres were identified. One patient appeared to have levamisole-induced vasculitis, with raised proteinase 3, perinuclear antineutrophil cytoplasmic antibodies positivity and arthralgia which improved on systemic steroids. The other eight patients had features of a cocaine-induced midline destructive lesion.
As the use of cocaine increases, ENT surgeons will see more of the complications associated with it. This paper highlights some of the diagnostic issues and proposes a management strategy as a guide to this complex patient group. Often, multidisciplinary management is needed.
Background: Since January 1, 2016 2358 people have died from opioid poisoning in Alberta. Buprenorphine/naloxone (bup/nal) is the recommended first line treatment for opioid use disorder (OUD) and this treatment can be initiated in emergency departments and urgent care centres (EDs). Aim Statement: This project aims to spread a quality improvement intervention to all 107 adult EDs in Alberta by March 31, 2020. The intervention supports clinicians to initiate bup/nal for eligible individuals and provide rapid referrals to OUD treatment clinics. Measures & Design: Local ED teams were identified (administrators, clinical nurse educators, physicians and, where available, pharmacists and social workers). Local teams were supported by a provincial project team (project manager, consultant, and five physician leads) through a multi-faceted implementation process using provincial order sets, clinician education products, and patient-facing information. We used administrative ED and pharmacy data to track the number of visits where bup/nal was given in ED, and whether discharged patients continued to fill any opioid agonist treatment (OAT) prescription 30 days after their index ED visit. OUD clinics reported the number of referrals received from EDs and the number attending their first appointment. Patient safety event reports were tracked to identify any unintended negative impacts. Evaluation/Results: We report data from May 15, 2018 (program start) to September 31, 2019. Forty-nine EDs (46% of 107) implemented the program and 22 (45% of 49) reported evaluation data. There were 5385 opioid-related visits to reporting ED sites after program adoption. Bup/nal was given during 832 ED visits (663 unique patients): 7 visits in the 1st quarter the program operated, 55 in the 2nd, 74 in the 3rd, 143 in the 4th, 294 in the 5th, and 255 in the 6th. Among 505 unique discharged patients with 30 day follow up data available 319 (63%) continued to fill any OAT prescription after receiving bup/nal in ED. 16 (70%) of 23 community clinics provided data. EDs referred patients to these clinics 440 times, and 236 referrals (54%) attended their first follow-up appointment. Available data may under-report program impact. 5 patient safety events have been reported, with no harm or minimal harm to the patient. Discussion/Impact: Results demonstrate effective spread and uptake of a standardized provincial ED based early medical intervention program for patients who live with OUD.
Introduction: Determining fluid status prior to resuscitation provides a more accurate guide for appropriate fluid administration in the setting of undifferentiated hypotension. Emergency Department (ED) point of care ultrasound (PoCUS) has been proposed as a potential non-invasive, rapid, repeatable investigation to ascertain inferior vena cava (IVC) characteristics. Our goal was to determine the feasibility of using PoCUS to measure IVC size and collapsibility. Methods: This was a planned secondary analysis of data from a prospective multicentre international study investigating PoCUS in ED patients with undifferentiated hypotension. We prospectively collected data on IVC size and collapsibility using a standard data collection form in 6 centres. The primary outcome was the proportion of patients with a clinically useful (determinate) scan defined as a clearly visible intrahepatic IVC, measurable for size and collapse. Descriptive statistics are provided. Results: A total of 138 scans were attempted on 138 patients; 45.7% were women and the median age was 58 years old. Overall, one hundred twenty-nine scans (93.5%; 95% CI 87.9 to 96.7%) were determinate. 131 (94.9%; 89.7 to 97.7%) were determinate for IVC size, and 131 (94.9%; 89.7 to 97.7%) were determinate for collapsibility. Conclusion: In this analysis of 138 ED patients with undifferentiated hypotension, the vast majority of PoCUS scans to investigate IVC characteristics were determinate. Future work should include analysis of the value of IVC size and collapsibility in determining fluid status in this group.
To identify clusters of patients with post-traumatic stress disorder (PTSD) according to symptom profile and to examine the association of the A1 allele of the D2 dopamine receptor (DRD2) gene with these clusters.
Fifty-seven untreated Caucasian Vietnam veterans with PTSD were administered the General Health Questionnaire-28 (GHQ) and the Mississippi Scale for combat-related PTSD. DRD2 allelic status was determined by PCR.
Subjects with the DRD2 Al allele compared to those without this allele had significantly higher scores on GHQ 2 (anxiety/insomnia), GHQ 3 (social dysfunction) and GHQ 4 (depression). Cluster analysis of the GHQ data identified two primary groups. A high psychopathology cluster (cluster 3), featured by high co-morbid levels of somatic concerns, anxiety/insomnia, social dysfunction and depression, and a low psychopathology cluster (cluster 1), manifested by the reverse pattern. Scores in each of the four GHQ groups were significantly higher in cluster 3 than cluster 1, as was Mississippi Scale PTSD score. DRD2 A1 allele veterans compared to those without this allele were significantly more likely to be found in the high than the low psychopathology cluster group.
DRD2 variants are associated with severe co-morbid psychopathology in PTSD subjects.
[Improvement in daily accessible risk assessments]
We show enhanced patient safety through a quality improvement methodology project in an intensive psychiatric care unit of a psychiatric hospital in southwest of Scotland. This is a project as part of the national patient safety programme in mental health. The Scottish Patient Safety Programme for Mental Health aims to systematically reduce harm experienced by people using mental health services in Scotland, by supporting frontline staff to test, gather real-time data and reliably implement interventions, before spreading across their catchment area.
Multidisciplinary staff worked together in improving recording of daily electronic and paper based risk assessments from a baseline of 20% to nearly 100% over a sixth month period. We expect better quality risk management by readily accessible risk assessments and safe practise through enhanced safety perception by the patients as well as staff. Patient and staff safety perception tools were designed to measure impact of improvement in risk management. We have seen drop in the number of critical incidents and challenging situations requiring restraint following coordinated approach to risk assessment and easy access to key information. We have been successful as the frontline staff became part of the process of change and this has enabled sustained improvement.
Novel tools for early diagnosis and monitoring of schistosomiasis are urgently needed. This study aimed to validate parasite-derived miRNAs as potential novel biomarkers for the detection of human Schistosoma japonicum infection. A total of 21 miRNAs were initially validated by real-time-polymerase chain reaction (RT-PCR) using serum samples of S. japonicum-infected BALB/c mice. Of these, 6 miRNAs were further validated with a human cohort of individuals from a schistosomiasis-endemic area of the Philippines. RT-PCR analysis showed that two parasite-derived miRNAs (sja-miR-2b-5p and sja-miR-2c-5p) could detect infected individuals with low infection intensity with moderate sensitivity/specificity values of 66%/68% and 55%/80%, respectively. Analysis of the combined data for the two parasite miRNAs revealed a specificity of 77.4% and a sensitivity of 60.0% with an area under the curve (AUC) value of 0.6906 (P = 0.0069); however, a duplex RT-PCR targeting both sja-miR-2b-5p and sja-miR-2c-5p did not result in an increased diagnostic performance compared with the singleplex assays. Furthermore, the serum level of sja-miR-2c-5p correlated significantly with faecal egg counts, whereas the other five miRNAs did not. Targeting S. japonicum-derived miRNAs in serum resulted in a moderate diagnostic performance when applied to a low schistosome infection intensity setting.
In vitro production (IVP) of embryos and associated technologies in cattle have shown significant progress in recent years, in part driven by a better understanding of the full potential of these tools by end users. The combination of IVP with sexed semen (SS) and genomic selection (GS) is being successfully and widely used in North America, South America and Europe. The main advantages offered by these technologies include a higher number of embryos and pregnancies per unit of time, and a wider range of potential female donors from which to retrieve oocytes (including open cyclic females and ones up to 3 months pregnant), including high index genomic calves, a reduced number of sperm required to produce embryos and increased chances of obtaining the desired sex of offspring. However, there are still unresolved aspects of IVP of embryos that limit a wider implementation of the technology, including potentially reduced fertility from the use of SS, reduced oocyte quality after in vitro oocyte maturation and lower embryo cryotolerance, resulting in reduced pregnancy rates compared to in vivo–produced embryos. Nevertheless, promising research results have been reported, and work is in progress to address current deficiencies. The combination of GS, IVP and SS has proven successful in the commercial field in several countries assisting practitioners and cattle producers to improve reproductive performance, efficiency and genetic gain.
The hemlock woolly adelgid (Hemiptera: Adelgidae: Adelges tsugae Annand) is an invasive insect, introduced from Japan to eastern North America, where it causes decline and death of hemlock trees. There is a closely related lineage of A. tsugae native to western North America. To inform classical biological control of A. tsugae in the eastern USA, the density and phenology of three native western adelgid specialist predators, Leucopis argenticollis (Zetterstedt), Le. piniperda (Malloch) (Diptera: Chamaemyiidae), and Laricobius nigrinus Fender (Coleoptera: Derodontidae), were quantified in the Pacific Northwest. Infested branches were collected from western hemlock (Pinaceae: Tsuga heterophylla (Raf.) Sarg.) at four sites around the Puget Sound, Washington and three sites in Oregon. Immature Leucopis were identified to species using DNA barcodes. Leucopis argenticollis was roughly twice as abundant as Le. piniperda. Laricobius nigrinus larvae were more abundant than the two species of Leucopis during the egg stage of the first adelgid generation, but Leucopis were present as feeding larvae during the second adelgid generation when La. nigrinus was aestivating in the soil, resulting in Leucopis being more abundant than La. nigrinus across the entire sampling period. Adelges tsugae and La. nigrinus densities were not correlated, while A. tsugae and Leucopis spp. densities were positively correlated. Leucopis spp. and La. nigrinus densities were negatively correlated. These results support the complementary use of La. nigrinus and the two Leucopis species for biological control of A. tsugae in the eastern USA, and point to the need for further investigation of spatial and temporal niche partitioning among the three predator species.
Many studies have reported associations between prenatal stress and the development of psychotic, anxiety and depressive disorders; however, to date no studies have investigated potential associations with personality disorders.
This study investigated potential associations between exposure to prenatal stress and personality disorder in offspring.
In a subsample (N = 3626) of a large Finnish birth cohort, we used logistic regression models to examine associations between self-reported maternal stress during pregnancy, collected monthly during antenatal clinic appointments, and personality disorder in offspring. Familial and outcome information were obtained by linking data from the Finnish Hospital Discharge Register and the Finnish Population Register.
Compared with those unexposed, children exposed to any maternal stress during gestation had three times the odds of developing a personality disorder (odds ratio 2.76, 95% CI 1.59–4.80, P = 0.000). Those exposed to moderate stress had three times the odds (odds ratio 3.13, 95% CI 1.42–6.88, P = 0.005) and those exposed to severe stress had seven times the odds (odds ratio 7.06, 95% CI 2.10–23.81, P = 0.002) of developing a personality disorder. These associations remained after adjusting for parental psychiatric history, comorbid psychiatric diagnoses, prenatal smoking and antenatal depression.*
Exposure to stress during gestation increases the odds of personality disorder in offspring, independent of other psychiatric disorders. These results suggest the assessment of maternal stress and well-being during pregnancy may be useful in identifying those at greatest risk of developing personality disorder, and highlight the importance of prenatal care for good maternal mental health during pregnancy.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Background: Buprenorphine/naloxone (bup/nal) is a partial opioid agonist/antagonist and recommended first line treatment for opioid use disorder (OUD). Emergency departments (EDs) are a key point of contact with the healthcare system for patients living with OUD. Aim Statement: We implemented a multi-disciplinary quality improvement project to screen patients for OUD, initiate bup/nal for eligible individuals, and provide rapid next business day walk-in referrals to addiction clinics in the community. Measures & Design: From May to September 2018, our team worked with three ED sites and three addiction clinics to pilot the program. Implementation involved alignment with regulatory requirements, physician education, coordination with pharmacy to ensure in-ED medication access, and nurse education. The project is supported by a full-time project manager, data analyst, operations leaders, physician champions, provincial pharmacy, and the Emergency Strategic Clinical Network leadership team. For our pilot, our evaluation objective was to determine the degree to which our initiation and referral pathway was being utilized. We used administrative data to track the number of patients given bup/nal in ED, their demographics and whether they continued to fill bup/nal prescriptions 30 days after their ED visit. Addiction clinics reported both the number of patients referred to them and the number of patients attending their referral. Evaluation/Results: Administrative data shows 568 opioid-related visits to ED pilot sites during the pilot phase. Bup/nal was given to 60 unique patients in the ED during 66 unique visits. There were 32 (53%) male patients and 28 (47%) female patients. Median patient age was 34 (range: 21 to 79). ED visits where bup/nal was given had a median length of stay of 6 hours 57 minutes (IQR: 6 hours 20 minutes) and Canadian Triage Acuity Scores as follows: Level 1 – 1 (2%), Level 2 – 21 (32%), Level 3 – 32 (48%), Level 4 – 11 (17%), Level 5 – 1 (2%). 51 (77%) of these visits led to discharge. 24 (47%) discharged patients given bup/nal in ED continued to fill bup/nal prescriptions 30 days after their index ED visit. EDs also referred 37 patients with OUD to the 3 community clinics, and 16 of those individuals (43%) attended their first follow-up appointment. Discussion/Impact: Our pilot project demonstrates that with dedicated resources and broad institutional support, ED patients with OUD can be appropriately initiated on bup/nal and referred to community care.
Supermassive black holes are found in most galactic nuclei. A large fraction of these nuclei also contain a nuclear stellar cluster surrounding the black hole. Here we consider the idea that the nuclear stellar cluster formed first and that the supermassive black hole grew later. In particular we consider the merger of three stellar clusters to form a nuclear stellar cluster, where some of these clusters contain a single intermediate-mass black hole (IMBH). In the cases where multiple clusters contain IMBHs, we discuss whether the black holes are likely to merge and whether such mergers are likely to result in the ejection of the merged black hole from the nuclear stellar cluster. In some cases, no supermassive black hole will form as any merger product is not retained. This is a natural pathway to explain those galactic nuclei that contain a nuclear stellar cluster but apparently lack a supermassive black hole; M33 being a nearby example. Alternatively, if an IMBH merger product is retained within the nuclear stellar cluster, it may subsequently grow, e.g. via the tidal disruption of stars, to form a supermassive black hole.
Emotion dysregulation is defined as patterns of emotional experience or expression that interfere with goal-directed activity. This paper considers this functionalist definition from a developmental perspective with the goal of elaborating this approach with respect to its central questions. What are the goals that are impeded by emotionally dysregulated responding, and what alternative goals might motivate emotion dysregulation? What are the developmental processes by which these goals take shape, and what are the influences of the family context, and especially of central relationships in the family, in their emergence? How does this functionalist account address the complex interaction of experience and developing biological processes that also influence emotion regulation and dysregulation? Drawing on research literature concerning children at risk for affective psychopathology and considering relevant examples of the interaction of biology and context, this discussion offers a portrayal of emotion dysregulation as a biologically dynamic, experience-based aspect of adaptation to environments and relationships that, in conditions of risk for the emergence of developmental psychopathology, motivates patterns of emotional responding that serve immediate coping often at the cost of long-term maladaptation. Implications for emotions theory and the study of developmental psychopathology are also considered.
Balloon atrial septostomy is performed in infants with dextro-transposition of the great arteries to improve oxygenation before surgery. It is performed in the catheterisation laboratory with fluoroscopy or at the bedside using echocardiography. It is unclear whether procedural safety and efficacy is superior in one location versus the other, although the bedside procedure may improve resource utilisation and present an opportunity for reducing cost. This study compares safety and efficacy of atrial septostomy performed at the patient’s bedside versus the catheterisation laboratory.
Neonates with dextro-transposition of the great arteries who underwent balloon atrial septostomy from October, 2000 to January, 2014 were included. Medical and procedural records, echocardiograms, and catheterisation data were reviewed. Comparisons between the two procedural locations included patient demographics, pre- and post-procedure oxygen saturations, and outcomes. Complications reviewed included bleeding, arrhythmia, cardiac trauma, stroke, and death. Coronary artery evaluations were recorded. T-tests were used for continuous variables, and Fisher’s exact tests were used for all categorical variables. Wilcoxon rank sum and analysis of covariance modelling were used for time variables and oxygen saturation, respectively.
A total of 88 infants met the inclusion criteria. Among them, 53 underwent septostomy at the bedside and 35 underwent septostomy in the catheterisation laboratory. No safety or outcome benefit was identified between the two procedural locations.
Septostomy performed at the bedside and in the catheterisation laboratory had similar outcomes and efficacy. Further, bedside septostomy has the advantage of no radiation exposure, and obviating risks with patient transfer from the ICU to the catheterisation laboratory.
We commend Rotolo et al. (2018) for introducing a new lens for viewing the well-known gap between industrial and organizational (I-O) psychology research and human resource (HR) practices in organizations. However, Rotolo et al.’s characterization of practitioner behavior as “anti I-O” suggests a particularly negative view of scientific research among some HR practitioners. The label implies that some HR practitioners are intentionally ignoring or actively resisting academic research. More likely, the behavior stems from a passive indifference to academia, which may be the appropriate attitude for some practitioners to adopt when a great deal of academic research is too slow, too theoretical, and too cryptically communicated to be useful in applied settings. We agree with Rotolo et al. when they say, “we are a discipline that is not geared for being cutting edge” (p. 182), and we appreciate their recommendations for addressing this lack of relevance. However, most recommendations in this broader discussion do not address the foundational problem within our field: a systemic mismatch between the incentives of practitioners and academics. To support this point, we briefly describe a typology of I-O psychologists as well as the varying contexts and incentives that drive their behavior. We then close with our own recommendations for how academia can improve its relevance to practitioners and close the gap. These changes are not easy, but we agree with Rotolo and colleagues that if any field can address such foundational problems, it is ours.
Background: Heterozygous loss-of-function mutations in the synaptic scaffolding gene SHANK2 are strongly associated with autism spectrum disorder (ASD). However, their impact on the function of human neurons is unknown. Derivation of induced pluripotent stem cells (iPSC) from affected individuals permits generation of live neurons to answer this question. Methods: We generated iPSCs by reprogramming dermal fibroblasts of neurotypic and ASD-affected donors. To isolate the effect of SHANK2, we used CRISPR/Cas9 to knock out SHANK2 in control iPSCs and correct a heterozygous nonsense mutation in ASD-affected donor iPSCs. We then derived cortical neurons from SOX1+ neural precursor cells differentiated from these iPSCs. Using a novel assay that overcomes line-to-line variability, we compared neuronal morphology, total synapse number, and electrophysiological properties between SHANK2 mutants and controls. Results: Relative to controls, SHANK2 mutant neurons have increased dendrite complexity, dendrite length, total synapse number (1.5-2-fold), and spontaneous excitatory postsynaptic current (sEPSC) frequency (3-7.6-fold). Conclusions: ASD-associated heterozygous loss-of-function mutations in SHANK2 increase synaptic connectivity among human neurons by increasing synapse number and sEPSC frequency. This is partially supported by increased dendrite length and complexity, providing evidence that SHANK2 functions as a suppressor of dendrite branching during neurodevelopment.
Twin pregnancies discordant for neural tube defects (NTD) is a management dilemma. Risks of preterm delivery from polyhydramnios must be balanced with the risks of selective termination (ST) of the anomalous fetus. We investigated the prevalence of twin pregnancies discordant for NTD and the rate of pregnancy complications in our institution over a 10-year period. Cases were obtained by searching the hospital ultrasound database and findings were confirmed by expert review of ultrasound images. Outcomes of ST and expectant management were assessed. Each unaffected co-twin was assigned to three consecutive twin pregnancy controls matched by chorionicity and maternal age. Primary outcome was birth before 34 weeks’ gestation. Secondary outcomes were small for gestational age, mode of delivery, neonatal unit admission, and neonatal death. In total, 13 pregnancies were identified as potential cases. Of these, 11 were included in the analysis: 9 dichorionic diamniotic and 2 monochorionic diamniotic twins. Seven cases had ST and four were managed expectantly. We found 100% (4/4) of expectantly managed pregnancies delivered <34 weeks compared with 14% (1/7) of the ST group (p = .015). Polyhydramnios complicated three expectantly managed pregnancies and one pregnancy in the ST group. The birthweight SD score of all unaffected co-twins was ≥-2. The case–control analysis showed a higher rate of polyhydramnios in twin pregnancies discordant for NTD compared with controls, but little evidence for differences between groups in delivery rates <34 weeks, birthweight, neonatal unit admission, or neonatal death. ST warrants serious consideration to avoid potential complications to the unaffected co-twin.
Research into the gut microbiota of human infants is necessary in order to better understand how inter-species interactions and ecological succession shape the diversity of the gut microbiota, and in turn, how the specific composition of the gut microbiota impacts on host health both during infancy and in later years. Blastocystis is a ubiquitous intestinal protist that has been linked to a number of intestinal and extra-intestinal diseases. However, emerging data show that asymptomatic carriage is common and that Blastocystis is prevalent in the healthy adult gut microbiota. Nonetheless, little is known about the prevalence and diversity of this microorganism in the healthy infant gut, including when and how individuals become colonized by Blastocystis. Here, we surveyed the prevalence and diversity of Blastocystis in an infant population (n = 59) from an industrialized country (Ireland) using Blastocystis-specific primers at three or more time-points up to 24 months old. Only three infants were positive for Blastocystis (prevalence = 5%) and this was only noted for samples collected at month 24. This rate is comparatively low relative to previously reported prevalence rates in the contemporaneous adult population. These data suggest that infants in Westernized countries that are successfully colonized by Blastocystis most likely acquire this microorganism via horizontal transfer.
n-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3−)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3− male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3− offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3− animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes.