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Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), could lead to more targeted treatments to reduce risk.
Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups.
Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1–4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79–88%).
These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.
The SCN5A gene is implicated in many arrhythmogenic and cardiomyopathic processes. We identified a novel SCN5A variant in a family with significant segregation in individuals affected with progressive sinus and atrioventricular nodal disease, atrial arrhythmia, dilated cardiomyopathy, and early sudden cardiac arrest.
A patient pedigree was created following the clinical evaluation of three affected individuals, two monozygotic twins and a paternal half-brother, which lead to the evaluation of a paternal half-sister (four siblings with the same father and three mothers) all of whom experienced varying degrees of atrial arrhythmias, conduction disease, and dilated cardiomyopathy in addition to a paternal history of unexplained death in his 50s with similar autopsy findings. The index male underwent sequencing of 58 genes associated with cardiomyopathies. Sanger sequencing was used to provide data for bases with insufficient coverage and for bases in some known regions of genomic segmental duplications. All clinically significant and novel variants were confirmed by independent Sanger sequencing.
All relatives tested were shown to have the same SCN5A variant of unknown significance (p. Asp197His) and the monozygotic twins shared a co-occurring NEXN (p. Glu575*). Segregation analysis demonstrates likely pathogenic trait for the SCN5A variant with an additional possible role for the NEXN variant in combination.
There is compelling clinical evidence suggesting that the SCN5A variant p. Asp197His may be re-classified as likely pathogenic based on the segregation analysis of our family of interest. Molecular mechanism studies are pending.
Angiostrongylus cantonensis is a pathogenic nematode and the cause of neuroangiostrongyliasis, an eosinophilic meningitis more commonly known as rat lungworm disease. Transmission is thought to be primarily due to ingestion of infective third stage larvae (L3) in gastropods, on produce, or in contaminated water. The gold standard to determine the effects of physical and chemical treatments on the infectivity of A. cantonensis L3 larvae is to infect rodents with treated L3 larvae and monitor for infection, but animal studies are laborious and expensive and also raise ethical concerns. This study demonstrates propidium iodide (PI) to be a reliable marker of parasite death and loss of infective potential without adversely affecting the development and future reproduction of live A. cantonensis larvae. PI staining allows evaluation of the efficacy of test substances in vitro, an improvement upon the use of lack of motility as an indicator of death. Some potential applications of this assay include determining the effectiveness of various anthelmintics, vegetable washes, electromagnetic radiation and other treatments intended to kill larvae in the prevention and treatment of neuroangiostrongyliasis.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Maternal mental health during pregnancy and postpartum predicts later emotional and behavioural problems in children. Even though most perinatal mental health problems begin before pregnancy, the consequences of preconception maternal mental health for children's early emotional development have not been prospectively studied.
We used data from two prospective Australian intergenerational cohorts, with 756 women assessed repeatedly for mental health problems before pregnancy between age 13 and 29 years, and during pregnancy and at 1 year postpartum for 1231 subsequent pregnancies. Offspring infant emotional reactivity, an early indicator of differential sensitivity denoting increased risk of emotional problems under adversity, was assessed at 1 year postpartum.
Thirty-seven percent of infants born to mothers with persistent preconception mental health problems were categorised as high in emotional reactivity, compared to 23% born to mothers without preconception history (adjusted OR 2.1, 95% CI 1.4–3.1). Ante- and postnatal maternal depressive symptoms were similarly associated with infant emotional reactivity, but these perinatal associations reduced somewhat after adjustment for prior exposure. Causal mediation analysis further showed that 88% of the preconception risk was a direct effect, not mediated by perinatal exposure.
Maternal preconception mental health problems predict infant emotional reactivity, independently of maternal perinatal mental health; while associations between perinatal depressive symptoms and infant reactivity are partially explained by prior exposure. Findings suggest that processes shaping early vulnerability for later mental disorders arise well before conception. There is an emerging case for expanding developmental theories and trialling preventive interventions in the years before pregnancy.
Recent commercialization of auxin herbicide–based weed control systems has led to increased off-target exposure of susceptible cotton cultivars to auxin herbicides. Off-target deposition of dilute concentrations of auxin herbicides can occur on cotton at any stage of growth. Field experiments were conducted at two locations in Mississippi from 2014 to 2016 to assess the response of cotton at various growth stages after exposure to a sublethal 2,4-D concentration of 8.3 g ae ha−1. Herbicide applications occurred weekly from 0 to 14 weeks after emergence (WAE). Cotton exposure to 2,4-D at 2 to 9 WAE resulted in up to 64% visible injury, whereas 2,4-D exposure 5 to 6 WAE resulted in machine-harvested yield reductions of 18% to 21%. Cotton maturity was delayed after exposure 2 to 10 WAE, and height was increased from exposure 6 to 9 WAE due to decreased fruit set after exposure. Total hand-harvested yield was reduced from 2,4-D exposure 3, 5 to 8, and 13 WAE. Growth stage at time of exposure influenced the distribution of yield by node and position. Yield on lower and inner fruiting sites generally decreased from exposure, and yield partitioned to vegetative or aborted positions and upper fruiting sites increased. Reductions in gin turnout, micronaire, fiber length, fiber-length uniformity, and fiber elongation were observed after exposure at certain growth stages, but the overall effects on fiber properties were small. These results indicate that cotton is most sensitive to low concentrations of 2,4-D during late vegetative and squaring growth stages.
Synchrotron white beam transmission topography of GaAs as previously reported by the authors relied on scanning specimen and film synchronously through the incident x-ray beam to record transmission topographic images en film. Sometimes the total dose required for reasonable contrast on film carried with it enough thermal deposition to cause elastic warping of the wafer. To escape these problems, a real time system was assembled. This system included an image intensifier, a solid state camera, a computer board to frame-grab and digitize images, and appropriate image processing software. With this system, a three inch specimen was scanned from edge to edge in one minute. At this scan rate, the incident x-ray beam had to be significantly attenuated to avoid saturating the intensifier output.
The crystal structure of tlapallite has been determined using single-crystal X-ray diffraction and supported by electron probe micro-analysis, powder diffraction and Raman spectroscopy. Tlapallite is trigonal, space group P321, with a = 9.1219(17) Å, c = 11.9320(9) Å and V = 859.8(3) Å3, and was refined to R1 = 0.0296 for 786 reflections with I > 2σ(I). This study resulted from the discovery of well-crystallised tlapallite at the Wildcat prospect, Utah, USA. The chemical formula of tlapallite has been revised to (Ca,Pb)3CaCu6[Te4+3Te6+O12]2(Te4+O3)2(SO4)2·3H2O, or more simply (Ca,Pb)3CaCu6Te4+8Te6+2O30(SO4)2·3H2O, from H6(Ca,Pb)2(Cu,Zn)3(TeO3)4(TeO6)(SO4). The tlapallite structure consists of layers containing distorted Cu2+O6 octahedra, Te6+O6 octahedra and Te4+O4 disphenoids (which together form the new mixed-valence phyllotellurate anion [Te4+3Te6+O12]12−), Te4+O3 trigonal pyramids and CaO8 polyhedra. SO4 tetrahedra, Ca(H2O)3O6 polyhedra and H2O groups fill the space between the layers. Tlapallite is only the second naturally occurring compound containing tellurium in both the 4+ and 6+ oxidation states with a known crystal structure, the other being carlfriesite, CaTe4+2Te6+O8. Carlfriesite is the predominant secondary tellurium mineral at the Wildcat prospect. We also present an updated structure for carlfriesite, which has been refined to R1 = 0.0230 for 874 reflections with I > 2σ(I). This updated structural refinement improves upon the one reported previously by refining all atoms anisotropically and presenting models of bond valence and Te4+ secondary bonding.
The introduction of auxin herbicide weed control systems has led to increased occurrence of crop injury in susceptible soybeans and cotton. Off-target exposure to sublethal concentrations of dicamba can occur at varying growth stages, which may affect crop response. Field experiments were conducted in Mississippi in 2014, 2015, and 2016 to characterize cotton response to a sublethal concentration of dicamba equivalent to 1/16X the labeled rate. Weekly applications of dicamba at 35 g ae ha−1 were made to separate sets of replicated plots immediately following planting until 14 wk after emergence (WAE). Exposure to dicamba from 1 to 9 WAE resulted in up to 32% visible injury, and exposure from 7 to 10 WAE delayed crop maturity. Exposure from 8 to 10 and 13 WAE led to increased cotton height, while an 18% reduction in machine-harvested yield resulted from exposure at 6 WAE. Cotton exposure at 3 to 9 WAE reduced the seed cotton weight partitioned to position 1 fruiting sites, while exposure at 3 to 6 WAE also reduced yield in position 2 fruiting sites. Exposure at 2, 3, and 5 to 7 WAE increased the percent of yield partitioned to vegetative branches. An increase in percent of yield partitioned to plants with aborted terminals occurred following exposure from 3 to 7 WAE and corresponded with reciprocal decreases in yield partitioned to positional fruiting sites. Minimal effects were observed on fiber quality, except for decreases in fiber length uniformity resulting from exposure at 9 and 10 WAE.
The Canadian Stroke Best Practice Recommendations suggests that patients suspected of transient ischemic attack (TIA)/minor stroke receive urgent brain imaging, preferably computed tomography angiography (CTA). Yet, high requisition rates for non-cerebrovascular patients overburden limited radiological resources, putting patients at risk. We hypothesize that our clinical decision support tool (CDST) developed for risk stratification of TIA in the emergency department (ED), and which incorporates Canadian guidelines, could improve CTA utilization.
Retrospective study design with clinical information gathered from ED patient referrals to an outpatient TIA unit in Victoria, BC, from 2015-2016. Actual CTA orders by ED and TIA unit staff were compared to hypothetical CTA ordering if our CDST had been used in the ED upon patient arrival.
For 1,679 referrals, clinicians ordered 954 CTAs. Our CDST would have ordered a total of 977 CTAs for these patients. Overall, this would have increased the number of imaged-TIA patients by 89 (10.1%) while imaging 98 (16.1%) fewer non-cerebrovascular patients over the 2-year period. Our CDST would have ordered CTA for 18 (78.3%) of the recurrent stroke patients in the sample.
Our CDST could enhance CTA utilization in the ED for suspected TIA patients, and facilitate guideline-based stroke care. Use of our CDST would increase the number of TIA patients receiving CTA before ED discharge (rather than later at TIA units) and reduce the burden of imaging stroke mimics in radiological departments.
This study aimed to identify the factors that counsellors working with refugees and asylum seekers in Australia consider influence their wellbeing and effectiveness. Nine employees in counsellor roles were interviewed. Thematic analysis indicated that government policies and practices were the greatest challenge. Factors facilitating effectiveness and wellbeing included having clear values, being able to see results for the client, receiving organisational support, working in a positive organisational culture, and having the support of family and friends. Factors inhibiting wellbeing included personal pressure to exert change, counsellor experience, feeling alienated from the community, lack of supervision, unclear organisational guidelines, and organisational values not being upheld. Along with the reported negative impact, positive psychological transformation was also reported. Through reflection on their clients’ strengths and resilience, participants reported feeling inspired, with increased effectiveness and wellbeing rather than vicarious trauma. This research contributes to the discussion about the psychologically harmful effects of government refugee and asylum seeker policy on counsellors and their clients.
Bacterial cultures exposed to iron-doped apatite nanoparticles (IDANPs) prior to the introduction of antagonistic viruses experience up to 2.3 times the bacterial destruction observed in control cultures. Maximum antibacterial activity of these bacteria-specific viruses, or phage, occurs after bacterial cultures have been exposed to IDANPs for 1 hr prior to phage introduction, demonstrating that IDANP-assisted phage therapy would not be straight forward, but would instead require controlled time release of IDANPs and phage. These findings motivated the design of an electrospun nanofiber mesh treatment delivery system that allows burst release of IDANPs, followed by slow, consistent release of phage for treatment of topical bacterial infections. IDANPs resemble hydroxyapatite, a biocompatible mineral analogous to the inorganic constituent of mammalian bone, which has been approved by the Food and Drug Administration for many biomedical purposes. The composite nanofiber mesh was designed for IDANP-assisted phage therapy treatment of topical wounds and consists of a superficial, rapid release layer of polyethylene oxide (PEO) fibers doped with IDANPs, followed by inner, coaxial polycaprolactone / polyethylene glycol (PCL/PEG) blended polymer fiber layer for slower phage delivery. Our investigations have established that IDANP-doped PEO fibers are effective vehicles for dissemination of IDANPs for bacterial exposure and resultant increased bacterial death by phage. In this work, slower delivery of the phage behind IDANPs was accomplished using coaxial, electrospun fibers composed of PCL/PEG polymer blend.
Functionally graded materials (FGMs) in which the elemental composition intentionally varies with position can be fabricated using directed energy deposition additive manufacturing (AM). This work examines an FGM that is linearly graded from V to Invar 36 (64 wt% Fe, 36 wt% Ni). This FGM cracked during fabrication, indicating the formation of detrimental phases. The microstructure, composition, phases, and microhardness of the gradient zone were analyzed experimentally. The phase composition as a function of chemistry was predicted through thermodynamic calculations. It was determined that a significant amount of the intermetallic σ-FeV phase formed within the gradient zone. When the σ phase constituted the majority phase, catastrophic cracking occurred. The approach presented illustrates the suitability of using equilibrium thermodynamic calculations for the prediction of phase formation in FGMs made by AM despite the nonequilibrium conditions in AM, providing a route for the computationally informed design of FGMs.
For most patients, adenoviruses cause few acute health concerns and are often self-limiting. Patients who are immunocompromised or immunosuppressed, however, are at risk for disseminated adenovirus and suffer high morbidity and mortality, without well-defined treatment options. We report the case of a 9-month-old boy who was successfully treated for disseminated adenovirus infection with intravenous immunoglobulin and cidofovir 3 months post heart transplant, tailored to serum adenoviral load and clinical response. We emphasise the importance of early identification, monitoring, and a potentially novel treatment in the paediatric cardiac transplant population with disseminated adenovirus infection.
Highly anomalous platinum-group element (PGE) concentrations in the podiform chromitites at the Cliff and Harold's Grave localities in the Shetland ophiolite complex have been well documented previously. The focus of this study is alluvial platinum-group minerals (PGM) located in small streams that drain from the PGE-rich chromitites. The placer PGM assemblage at Cliff is dominated by Pt-arsenides (64%) and Pd-antimonides (17%), with less irarsite–hollingworthite (11%) and minor Pd-sulfides, Pt–Pd–Cu and Pt–Fe alloys and laurite. Gold also occurs with the PGM. Alluvial PGM have average sizes of 20 µm × 60 µm, with sperrylite the largest grain identified at 110 µm in diameter, matching the range reported for the primary PGM in the source rocks. The placer assemblage contains more Pt-bearing and less Pd-bearing PGM compared with the rocks. The more resistant sperrylite and irarsite–hollingworthite grains which are often euhedral become more rounded further downstream whereas the less resistant Pd-antimonides which are commonly subhedral may become striated and etched. Less stable phases such as Pt- and Pd-oxides and other Ni-Cu-bearing phases located in the rocks (i.e. Ru-pentlandite, PtCu, Pd–Cu alloy) are absent in the placer assemblage. Also the scarce PGM (PdHg, Rh- and Ir-Sb) and Os in the rocks are absent. At Harold's Grave only three alluvial PGM (laurite, Ir, Os) and Au were recovered reflecting the limited release of IPGM from chromite grains in the rocks. In this cold climate with high rainfall, where erosion dominates over weathering, the PGM appear to have been derived directly from the erosion of the adjacent PGE-rich source rocks and there is little evidence of in situ growth of any newly formed PGM. Only the presence of dendritic pure Au and Pd-, Cu-bearing Au covers on the surface of primary minerals may indicate some local reprecipitation of these metals in the surficial conditions.