Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.

Electron Accumulation and Emergent Magnetism in LaMnO_{3}/SrTiO_{3} Heterostructures.

Emergent phenomena at polar-nonpolar oxide interfaces have been studied intensely in pursuit of next-generation oxide electronics and spintronics. Here we report the disentanglement of critical thicknesses for electron reconstruction and the emergence of ferromagnetism in polar-mismatched LaMnO_{3}/SrTiO_{3} (001) heterostructures. Using a combination of element-specific x-ray absorption spectroscopy and dichroism, and first-principles calculations, interfacial electron accumulation, and ferromagnetism have been observed within the polar, antiferromagnetic insulator LaMnO_{3}. Our results show that the critical thickness for the onset of electron accumulation is as thin as 2 unit cells (UC), significantly thinner than the observed critical thickness for ferromagnetism of 5 UC. The absence of ferromagnetism below 5 UC is likely induced by electron overaccumulation. In turn, by controlling the doping of the LaMnO_{3}, we are able to neutralize the excessive electrons from the polar mismatch in ultrathin LaMnO_{3} films and thus enable ferromagnetism in films as thin as 3 UC, extending the limits of our ability to synthesize and tailor emergent phenomena at interfaces and demonstrating manipulation of the electronic and magnetic structures of materials at the shortest length scales.

Functional electronic inversion layers at ferroelectric domain walls.

Ferroelectric domain walls hold great promise as functional two-dimensional materials because of their unusual electronic properties. Particularly intriguing are the so-called charged walls where a polarity mismatch causes local, diverging electrostatic potentials requiring charge compensation and hence a change in the electronic structure. These walls can exhibit significantly enhanced conductivity and serve as a circuit path. The development of all-domain-wall devices, however, also requires walls with controllable output to emulate electronic nano-components such as diodes and transistors. Here we demonstrate electric-field control of the electronic transport at ferroelectric domain walls. We reversibly switch from resistive to conductive behaviour at charged walls in semiconducting ErMnO3. We relate the transition to the formation-and eventual activation-of an inversion layer that acts as the channel for the charge transport. The findings provide new insight into the domain-wall physics in ferroelectrics and foreshadow the possibility to design elementary digital devices for all-domain-wall circuitry.

Fabrication and design of metal nano-accordion structures using atomic layer deposition and interference lithography.

Metal nanostructures have attractive electrical and thermal properties as well as structural stability, and are important for applications in flexible conductors. In this study, we have developed a method to fabricate and control novel complex platinum nanostructures with accordion-like profile using atomic layer deposition on lithographically patterned polymer templates. The template removal process results in unique structural transformation of the nanostructure profile, which has been studied and modeled. Using different template duty cycles and aspect ratios, we have demonstrated a wide variety of cross-sectional profiles from wavy geometry to pipe array patterns. These complex thin metal nanostructures can find applications in flexible/stretchable electronics, photonics and nanofluidics.

Atomically precise interfaces from non-stoichiometric deposition.

Complex oxide heterostructures display some of the most chemically abrupt, atomically precise interfaces, which is advantageous when constructing new interface phases with emergent properties by juxtaposing incompatible ground states. One might assume that atomically precise interfaces result from stoichiometric growth. Here we show that the most precise control is, however, obtained by using deliberate and specific non-stoichiometric growth conditions. For the precise growth of Sr(n+1)Ti(n)O(n+1) Ruddlesden-Popper (RP) phases, stoichiometric deposition leads to the loss of the first RP rock-salt double layer, but growing with a strontium-rich surface layer restores the bulk stoichiometry and ordering of the subsurface RP structure. Our results dramatically expand the materials that can be prepared in epitaxial heterostructures with precise interface control--from just the n = ∞ end members (perovskites) to the entire RP homologous series--enabling the exploration of novel quantum phenomena at a richer variety of oxide interfaces.

Nature of the metal insulator transition in ultrathin epitaxial vanadium dioxide.

We have combined hard X-ray photoelectron spectroscopy with angular dependent O K-edge and V L-edge X-ray absorption spectroscopy to study the electronic structure of metallic and insulating end point phases in 4.1 nm thick (14 units cells along the c-axis of VO2) films on TiO2(001) substrates, each displaying an abrupt MIT centered at ~300 K with width <20 K and a resistance change of ΔR/R > 10(3). The dimensions, quality of the films, and stoichiometry were confirmed by a combination of scanning transmission electron microscopy with electron energy loss spectroscopy, X-ray spectroscopy, and resistivity measurements. The measured end point phases agree with their bulk counterparts. This clearly shows that, apart from the strain induced change in transition temperature, the underlying mechanism of the MIT for technologically relevant dimensions must be the same as the bulk for this orientation.

Emergent properties of nanosensor arrays: applications for monitoring IgG affinity distributions, weakly affined hypermannosylation, and colony selection for biomanufacturing.

It is widely recognized that an array of addressable sensors can be multiplexed for the label-free detection of a library of analytes. However, such arrays have useful properties that emerge from the ensemble, even when monofunctionalized. As examples, we show that an array of nanosensors can estimate the mean and variance of the observed dissociation constant (KD), using three different examples of binding IgG with Protein A as the recognition site, including polyclonal human IgG (KD µ = 19 µM, σ(2) = 1000 mM(2)), murine IgG (KD µ = 4.3 nM, σ(2) = 3 µM(2)), and human IgG from CHO cells (KD µ = 2.5 nM, σ(2) = 0.01 µM(2)). Second, we show that an array of nanosensors can uniquely monitor weakly affined analyte interactions via the increased number of observed interactions. One application involves monitoring the metabolically induced hypermannosylation of human IgG from CHO using PSA-lectin conjugated sensor arrays where temporal glycosylation patterns are measured and compared. Finally, the array of sensors can also spatially map the local production of an analyte from cellular biosynthesis. As an example, we rank productivity of IgG-producing HEK colonies cultured directly on the array of nanosensors itself.

LaAlO3 stoichiometry is key to electron liquid formation at LaAlO3/SrTiO3 interfaces.

Emergent phenomena, including superconductivity and magnetism, found in the two-dimensional electron liquid (2-DEL) at the interface between the insulators lanthanum aluminate (LaAlO3) and strontium titanate (SrTiO3) distinguish this rich system from conventional 2D electron gases at compound semiconductor interfaces. The origin of this 2-DEL, however, is highly debated, with focus on the role of defects in the SrTiO3, while the LaAlO3 has been assumed perfect. Here we demonstrate, through experiments and first-principle calculations, that the cation stoichiometry of the nominal LaAlO3 layer is key to 2-DEL formation: only Al-rich LaAlO3 results in a 2-DEL. Although extrinsic defects, including oxygen deficiency, are known to render LaAlO3/SrTiO3 samples conducting, our results show that in the absence of such extrinsic defects an interface 2-DEL can form. Its origin is consistent with an intrinsic electronic reconstruction occurring to counteract a polarization catastrophe. This work provides insight for identifying other interfaces where emergent behaviours await discovery.

Utility of peripheral blood B cell subsets analysis in common variable immunodeficiency.

Abnormalities in peripheral blood B cell subsets have been identified in common variable immunodeficiency (CVID) patients and classification systems based upon their numbers have been proposed to predict the clinical features. We analysed B lymphocyte subsets by multi-colour flow cytometry (MFC) in a cohort of well-characterized CVID patients to look at their clinical relevance and validate the published association of different classification criteria (Freiburg, Paris and Euroclass) with clinical manifestations. CVID patients had a reduced proportion of total and switched memory B cells (MBC, swMBC) compared to normal controls (P < 0·0006). Patients classified in Freiburg Ia had a higher prevalence of granulomatous diseases (P = 0·0034). The previously published associations with autoimmune diseases could not be confirmed. The Euroclass classification was not predictive of clinical phenotypes. The absolute numbers of all B cell subsets were reduced in CVID patients compared to controls. There was a significant linear correlation between low absolute total B cells and MBC with granulomatous disease (P < 0·05) and a trend towards lower B cells in patients with autoimmune diseases (P = 0·07). Absolute number of different B cell subsets may be more meaningful than their relative percentages in assessing the risk of granulomatous diseases and possibly autoimmunity.

Short term outcomes after cardiac surgery in a Jehovah's Witness population: an institutional experience.

BACKGROUND: Minimising blood transfusion has a number of medical and logistical benefits, and is of particular importance for followers of the Jehovah's Witness faith. We examined the short term outcomes in this group of patients based on our institutional practice over the past decade. PATIENTS/METHODS: Data on 59 patients (73% male, mean age 66 years [range 40-83]) who identified as Jehovah's Witness was prospectively collected and retrospectively analysed from a systematised database over the period from January 1999 to June 2010. Mean logistic Euroscore was 4.5, with coronary artery bypass procedures most common (44/59, 75%) followed by aortic valve replacement (6/59, 10%). RESULTS: Average haemoglobin (Hb) fell from 142 g/L preoperatively to 109 g/L at discharge. Output from cardiac drains was reduced in patients who received aprotinin (34/59, 58%, p=0.05) compared to tranexaemic acid (11/59, 18%) or no antifibrinolytic (15/59, 25%). Operative mortality was 1/59 (1.7%) with an average length of postoperative stay of 6.2 days. Morbidity rates for neurologic deficit 2/59 (3.4%), deep sternal infection 1/59 (1.7%) and postoperative myocardial infarction 1/59 (1.7%) were within accepted ranges. CONCLUSION: Cardiac surgery can be performed safely in Jehovah's Witness patients with acceptable outcomes.

Role of autophagy in disease resistance and hypersensitive response-associated cell death.

Ancient autophagy pathways are emerging as key defense modules in host eukaryotic cells against microbial pathogens. Apart from actively eliminating intracellular intruders, autophagy is also responsible for cell survival, for example by reducing the deleterious effects of endoplasmic reticulum stress. At the same time, autophagy can contribute to cellular suicide. The concurrent engagement of autophagy in these processes during infection may sometimes mask its contribution to differing pro-survival and pro-death decisions. The importance of autophagy in innate immunity in mammals is well documented, but how autophagy contributes to plant innate immunity and cell death is not that clear. A few research reports have appeared recently to shed light on the roles of autophagy in plant-pathogen interactions and in disease-associated host cell death. We present a first attempt to reconcile the results of this research.

Morphological classification of plant cell deaths.

Programmed cell death (PCD) is an integral part of plant development and of responses to abiotic stress or pathogens. Although the morphology of plant PCD is, in some cases, well characterised and molecular mechanisms controlling plant PCD are beginning to emerge, there is still confusion about the classification of PCD in plants. Here we suggest a classification based on morphological criteria. According to this classification, the use of the term 'apoptosis' is not justified in plants, but at least two classes of PCD can be distinguished: vacuolar cell death and necrosis. During vacuolar cell death, the cell contents are removed by a combination of autophagy-like process and release of hydrolases from collapsed lytic vacuoles. Necrosis is characterised by early rupture of the plasma membrane, shrinkage of the protoplast and absence of vacuolar cell death features. Vacuolar cell death is common during tissue and organ formation and elimination, whereas necrosis is typically found under abiotic stress. Some examples of plant PCD cannot be ascribed to either major class and are therefore classified as separate modalities. These are PCD associated with the hypersensitive response to biotrophic pathogens, which can express features of both necrosis and vacuolar cell death, PCD in starchy cereal endosperm and during self-incompatibility. The present classification is not static, but will be subject to further revision, especially when specific biochemical pathways are better defined.

Chitosan/polyester-based scaffolds for cartilage tissue engineering: assessment of extracellular matrix formation.

Naturally derived polymers have been extensively used in scaffold production for cartilage tissue engineering. The present work aims to evaluate and characterize extracellular matrix (ECM) formation in two types of chitosan-based scaffolds, using bovine articular chondrocytes (BACs). The influence of these scaffolds' porosity, as well as pore size and geometry, on the formation of cartilagineous tissue was studied. The effect of stirred conditions on ECM formation was also assessed. Chitosan-poly(butylene succinate) (CPBS) scaffolds were produced by compression moulding and salt leaching, using a blend of 50% of each material. Different porosities and pore size structures were obtained. BACs were seeded onto CPBS scaffolds using spinner flasks. Constructs were then transferred to the incubator, where half were cultured under stirred conditions, and the other half under static conditions for 4 weeks. Constructs were characterized by scanning electron microscopy, histology procedures, immunolocalization of collagen type I and collagen type II, and dimethylmethylene blue assay for glycosaminoglycan (GAG) quantification. Both materials showed good affinity for cell attachment. Cells colonized the entire scaffolds and were able to produce ECM. Large pores with random geometry improved proteoglycans and collagen type II production. However, that structure has the opposite effect on GAG production. Stirred culture conditions indicate enhancement of GAG production in both types of scaffold.

The presence of leukaemia-associated phenotypes is an independent predictor of induction failure in acute myeloid leukaemia.

Immunophenotyping of acute myeloid leukaemia (AML) has controversial implications with regards to prognosis. The aims of the present study were to determine the frequency of leukaemia-associated phenotypes (LAP) in AML and to correlate their presence with response to induction chemotherapy. We analysed bone marrow samples at diagnosis from 84 AML patients using triple staining flow cytometry with routine standard panel of monoclonal antibodies. The association of LAP and response to induction chemotherapy was evaluated retrospectively. LAP were observed in 54 (64%) patients: lineage infidelity in 19 (35%), asynchronous antigen expression in 28 (52%), and lack of expected lineage specific antigens in 19 (35%). Significant correlation was found between LAP and responses to induction chemotherapy. Response to induction chemotherapy was more frequent in the absence of LAP (P < 0.05, estimated risk ratio of 1.6, 95%CI, 1.0-2.6) in a multivariate analysis. In conclusion, our data show the presence of LAP in AML is an independent predictor for response to induction chemotherapy and risk of relapse and should be considered for counselling patients and planning therapy.

A cartilage tissue engineering approach combining starch-polycaprolactone fibre mesh scaffolds with bovine articular chondrocytes.

In the present work we originally tested the suitability of corn starch-polycaprolactone (SPCL) scaffolds for pursuing a cartilage tissue engineering approach. Bovine articular chondrocytes were seeded on SPCL scaffolds under dynamic conditions using spinner flasks (total of 4 scaffolds per spinner flask using cell suspensions of 0.5 x 10(6) cells/ml) and cultured under orbital agitation for a total of 6 weeks. Poly(glycolic acid) (PGA) non-woven scaffolds and bovine native articular cartilage were used as standard controls for the conducted experiments. PGA is a kind of standard in tissue engineering approaches and it was used as a control in that sense. The tissue engineered constructs were characterized at different time periods by scanning electron microscopy (SEM), hematoxylin-eosin (H&E) and toluidine blue stainings, immunolocalisation of collagen types I and II, and dimethylmethylene blue (DMB) assay for glycosaminoglycans (GAG) quantification assay. SEM results for SPCL constructs showed that the chondrocytes presented normal morphological features, with extensive cells presence at the surface of the support structures, and penetrating the scaffolds pores. These observations were further corroborated by H&E staining. Toluidine blue and immunohistochemistry exhibited extracellular matrix deposition throughout the 3D structure. Glycosaminoglycans, and collagen types I and II were detected. However, stronger staining for collagen type II was observed when compared to collagen type I. The PGA constructs presented similar features to SPCL at the end of the 6 weeks. PGA constructs exhibited higher amounts of matrix glycosaminoglycans when compared to the SPCL scaffolds. However, we also observed a lack of tissue in the central area of the PGA scaffolds. Reasons for these occurrences may include inefficient cells penetration, necrosis due to high cell densities, or necrosis related with acidic by-products degradation. Such situation was not detected in the SPCL scaffolds, indicating the much better biocompatibility of the starch based scaffolds.

The imaginary line method is not reliable for identification of prosthetic heart valves on AP chest radiographs.

OBJECTIVE: To examine the utility of four criteria for distinguishing aortic from mitral valve prostheses on supine anteroposterior (AP) chest x rays in critically ill patients. MATERIALS AND METHODS: Two reviewers independently examined the post operative chest X-rays (CXR) of all patients undergoing either an aortic or mitral valve replacement over a 32 month period, in a blinded fashion. They applied four criteria to each film. For each criterion a sensitivity and specificity of differentiating the valve positions correctly was calculated for each reviewer, as well as a kappa statistic for inter-observer agreement between the two reviewers. RESULTS: Two hundred and twenty seven CXR's were evaluated by each of the reviewers. There were 174 aortic and 53 mitral valve replacements. There was a high level of inter-observer agreement for all four criteria applied (kappa values 0.785 to 0.966). Criterion one (imaginary line method) could be applied by both reviewers to less than 50% of CXR's, and when applied was specific but not sensitive. The other three criteria could be applied by both reviewers to approximately 80% of films. Criterion 2 (orientation method) was sensitive but not specific. Criteria 3 (valve orifice method) and 4 (perceived direction of blood flow method) were both highly sensitive and specific and are therefore the best methods. CONCLUSIONS: The well known imaginary line method is of limited value when identifying prosthetic valve positions on supine AP CXR's. We advocate the use of the "valve orifice" method or the "perceived direction of blood flow" method to gain valuable information regarding the presence and position of prosthetic heart valves.

Functional and prognostic implications of left ventricular contractile reserve in patients with asymptomatic severe mitral regurgitation.

OBJECTIVE: To evaluate contractile reserve (CR) determined by exercise echocardiography in predicting clinical outcome and left ventricular (LV) function in asymptomatic severe mitral regurgitation (MR). DESIGN: Cohort study. SETTING: Regional cardiac centre. PATIENTS AND OUTCOME MEASURES: LV volumes and ejection fraction (EF) were measured at rest and after stress in 71 patients with isolated MR. During follow up (mean (SD) 3 (1) years), EF and functional capacity were serially assessed and cardiac events (cardiac death, heart failure, and new atrial fibrillation) were documented. RESULTS: CR was present in 45 patients (CR+) and absent in 26 patients (CR-). Age, resting LV dimensions, EF, and MR severity were similar in both groups. Mitral surgery was performed in 19 of 45 (42%) CR+ patients and 22 of 26 (85%) CR- patients. In patients undergoing surgery, CR was an independent predictor of follow up EF (p = 0.006) and postoperative LV dysfunction (EF < 50%) persisted in five patients, all in the CR- group. Event-free survival was lower in surgically treated patients without CR (p = 0.03). In medically treated patients, follow up EF was preserved in those with intact CR but progressively deteriorated in patients without CR, in whom functional capacity also deteriorated. CONCLUSIONS: Evaluation of CR by exercise echocardiography may be useful for risk stratification and may help to optimise the timing of surgery in asymptomatic severe MR.

Fragmentations and reactions of the organophosphate insecticide Diazinon and its oxygen analog Diazoxon studied by electrospray ionization ion trap mass spectrometry.

The fragmentations and reactions of Diazinon and related compounds have been studied by electrospray ionization ion trap mass spectrometry. Several novel fragmentation and rearrangements have been observed, including an intramolecular thiono-thiolo rearrangement. The stability, in the gas-phase, of the protomers of 2-isopropyl-4-methyl-6-pyrimidinol has been demonstrated. The complexity of the gas phase ion processes observed suggest that, at present, caution should be exercised in using this approach for the analysis of environmental and other samples until our understanding of these processes increases considerably.

Control of specific gene expression by gibberellin and brassinosteroid.

We identified a recessive, brassinolide-insensitive mutant caused by a deletion allele (bri1-201) of the brassinosteroid (BR) receptor BRI1. The bri1-201 mutant displayed altered expression levels of genes differentially regulated by gibberellin (GA). RNA-blot analysis revealed that BR and GA antagonistically regulate the accumulation of mRNAs of the GA-responsive GASA1 gene, as well as the GA-repressible GA5 gene. Expression studies with cycloheximide indicated that the antagonistic effects of GA and BR on GA5 require de novo protein synthesis. Reporter transgene analyses and RNA-blot analysis showed that BR and GA modulate GA5 expression, at least in part, at the transcriptional level, and that the signals are independent and subtractive.

A magnetic resonance study of complicated early childhood convulsion.

OBJECTIVES: The relation between complicated early childhood convulsion (ECC) and adult epilepsy is unclear, although a history of complicated ECC is obtainable in half of adults with epilepsy associated with hippocampal sclerosis. It is not known if the ECC is a marker of pre-existing brain damage or is itself harmful to the developing brain. The objective of the study was to assess the extent of structural brain abnormality present soon after a first complicated early childhood convulsion with a view to obtaining data which might contribute to an understanding of whether such abnormalities were likely to be pre-existing or caused by the convulsion. METHODS: Children under the age of 5 years were recruited into the study after their first complicated febrile or non-febrile ECC. None had previously experienced an epileptic seizure. All underwent MRI of the brain within 14 days. Hippocampal volumes and T2 relaxation times were measured. The results were compared with a neurological control group of children without gross structural abnormalities of the neocortex undergoing MRI of the brain for reasons other than epilepsy. RESULTS: Eighteen patients and 10 control subjects were recruited into the study. One patient was subsequently excluded because of EEG and clinical evidence of benign childhood epilepsy. Nine patients had volumetric evidence of significant hippocampal volume asymmetry (3 SD from the mean of the control group), although in only three of these was the asymmetry apparent on visual inspection of the MRI. Three patients had extrahippocampal neuropathology. None of the control subjects had significant hippocampal volume asymmetry (p<0.001). T2 relaxometry showed no evidence that postictal hippocampal oedema contributed to the asymmetry. CONCLUSIONS: There is a high prevalence of structural brain abnormalities in children within 2 weeks of the first complicated early childhood convulsion, including significant hippocampal asymmetry unrelated to oedema. This does not exclude a damaging effect of complicated ECC on the brain, but suggests that in at least some patients the complicated ECC is the result of pre-existing brain abnormalities.