Use of a digital contact tracing system in Singapore to mitigate COVID-19 spread.

BACKGROUND: Contact tracing has been essential to reducing spread of COVID-19. Singapore leveraged technology to assist with contact tracing efforts using a Bluetooth-based app and token platform called 'TraceTogether'. METHODS: We reviewed the impact of this system during the country's Delta and Omicron waves (24 August 2021 to 17 February 2022) to identify differences in number of close contacts and time savings between full automation using TraceTogether alone as compared to manual contact tracing supplemented by TraceTogether. Characteristics of digital contact tracing app or token users were reviewed. Thereafter, the number of close contacts identified by manual and digital contact tracing methods, and the number of confirmed COVID-19 cases among contacts were analysed. The difference in time taken for identification of close contacts was also determined. FINDINGS: Adoption rate for TraceTogether was high, with 93.3% of cases having a registered device. There was a 9.8 h (34.9%) reduction in time savings for close contacts to be informed using TraceTogether alone compared to manual contact tracing supplemented by TraceTogether. The proportion of close contacts automatically identified through TraceTogether alone and turned positive was 3.6%. For those identified through manual contact tracing supplemented by TraceTogether, this proportion was 12.5% and 6.2% for those served quarantine orders and health risk warnings respectively. INTERPRETATION: The high adoption rate of 'TraceTogether' suggest that digital solutions remain a promising option to improve contact tracing in future epidemics. This may have been through its concurrent use with vaccine differentiated public health measures and policies which engender public trust. There is future potential for utilising such technology in managing communicable diseases to achieve good public health outcomes.

Dynamics of ultra-thin polystyrene with and without a (artificial) dead layer studied by resonance enhanced dynamic light scattering.

Using non-invasive, marker-free resonance enhanced dynamic light scattering, the dynamics of capillary waves on ultrathin polystyrene films' coupling to the viscoelastic and mechanical properties have been studied. The dynamics of ultrathin polymer films is still debated. In particular the question of what influence either the solid substrate and/or the fluid-gas interface has on the dynamics and the mechanical properties of films of glass forming liquids as polymers is in the focus of the present research. As a consequence, e.g., viscosity close to interfaces and thus the average viscosity of very thin films are prone to change. This study is focused on atactic, non-entangled polystyrene thin films on the gold surface. A slow dynamic mode was observed with Vogel-Fulcher-Tammann temperature dependence, slowing down with decreasing film thickness. We tentatively attribute this relaxation mode to overdamped capillary waves because of its temperature dependence and the dispersion with a wave vector which was found. No signs of a more mobile layer at the air/polymer interface or of a "dead layer" at the solid/polymer interface were found. Therefore we investigated the influence of an artificially created dead layer on the capillary wave dynamics by introducing covalently bound polystyrene polymer brushes as anchors. The dynamics was slowed down to a degree more than expected from theoretical work on the increase of density close to the solid liquid interface-instead of a "dead layer" of 2 nm, the interaction seems to extend more than 10 nm into the polymer.

A natural experiment study: Low-profile double plating versus single plating techniques in midshaft clavicle fractures-Study protocol.

BACKGROUND: Single plate osteosynthesis is commonly employed when performing surgical stabilization of midshaft clavicle fractures. In recent years, a smaller structural low-profile double plating technique has been described as a possible solution for the high removal rates associated with single plating. A previous meta-analysis has demonstrated that low-profile double plating attains the same healing rates as single plating without a higher chance of fracture-related infections. This meta-analysis, however, was based on relatively small studies. Therefore, a multicentre prospective natural experiment was designed using natural variation in treatment regimens and geographical location of the trauma as treatment allocation mechanism to compare both treatments on a larger scale. This manuscript describes its protocol. MATERIAL & METHODS: Patients (≥16 years) with primary midshaft clavicle fractures that are eligible for operative treatment will be included. Treatment allocation will be determined by the geographical location of the accident and local hospital providing treatment. In two centres, single plating is the treatment of choice for these patients. In two others, low-profile double plating has become the standard treatment. For the low-profile double plating group, one superiorly positioned VariAx 2.0mm and one anterior VariAx 2.4mm or 2.7mm plate will be used. For the single plating group, the standard locally available implant will be used. A total of 336 patients will be included. The primary outcome of interest is re-intervention. Secondary outcomes include complications, operative time, length of incision, functional scores (DASH, EQ-5D-DL, VAS-Pain/Satisfaction) and cost-effectiveness. DISCUSSION: This study will determine whether low-profile double plating has significant clinical and cost-effective benefits over single plating techniques in midshaft clavicle fractures. The study will also give insight in the performance of a natural experiment study design for orthopedic trauma research. TRIAL REGISTRATION: This study has been registered on ClincialTrials.gov, identifier NCT05579873.

Aster-free spindle poles in insect spermatocytes: evidence for chromosome-induced spindle formation?

Tipulid spermatocytes form normally functioning bipolar spindles after one of the centrosomes is experimentally dislocated from the nucleus in late diakinesis (Dietz, R., 1959, Z. Naturforsch., 14b:749-752; Dietz, R., 1963, Zool. Anz. Suppl., 23:131-138; Dietz, R., 1966, Heredity, 19:161-166). The possibility that dissociated pericentriolar material (PCM) is nevertheless responsible for the formation of the spindle in these cells cannot be ruled out based on live observation. In studying serial sections of complete cells and of lysed cells, it was found that centrosome-free spindle poles in the crane fly show neither pericentriolar-like material nor aster microtubules, whereas the displaced centrosomes appear complete, i.e., consist of a centriole pair, aster microtubules, and PCM. Exposure to a lysis buffer containing tubulin resulted in an increase of centrosomal asters due to aster microtubule polymerization. Aster-free spindle poles did not show any reaction, also indicating the absence of PCM at these poles. The results favor the hypothesis of chromosome-induced spindle pole formation at the onset of prometaphase and the dispensability of PCM in Pales.

Regulation of melanosome movement in the cell cycle by reversible association with myosin V.

Previously, we have shown that melanosomes of Xenopus laevis melanophores are transported along both microtubules and actin filaments in a coordinated manner, and that myosin V is bound to purified melanosomes (Rogers, S., and V.I. Gelfand. 1998. Curr. Biol. 8:161-164). In the present study, we have demonstrated that myosin V is the actin-based motor responsible for melanosome transport. To examine whether myosin V was regulated in a cell cycle-dependent manner, purified melanosomes were treated with interphase- or metaphase-arrested Xenopus egg extracts and assayed for in vitro motility along Nitella actin filaments. Motility of organelles treated with mitotic extract was found to decrease dramatically, as compared with untreated or interphase extract-treated melanosomes. This mitotic inhibition of motility correlated with the dissociation of myosin V from melanosomes, but the activity of soluble motor remained unaffected. Furthermore, we find that myosin V heavy chain is highly phosphorylated in metaphase extracts versus interphase extracts. We conclude that organelle transport by myosin V is controlled by a cell cycle-regulated association of this motor to organelles, and that this binding is likely regulated by phosphorylation of myosin V during mitosis.

The global carbon cycle: a test of our knowledge of earth as a system.

Motivated by the rapid increase in atmospheric CO2 due to human activities since the Industrial Revolution, several international scientific research programs have analyzed the role of individual components of the Earth system in the global carbon cycle. Our knowledge of the carbon cycle within the oceans, terrestrial ecosystems, and the atmosphere is sufficiently extensive to permit us to conclude that although natural processes can potentially slow the rate of increase in atmospheric CO2, there is no natural "savior" waiting to assimilate all the anthropogenically produced CO2 in the coming century. Our knowledge is insufficient to describe the interactions between the components of the Earth system and the relationship between the carbon cycle and other biogeochemical and climatological processes. Overcoming this limitation requires a systems approach.

Maternal temperament modulates curiosity and cortisol responses in farmed mink.

Early life events can shape the development of individual behavior and stress sensitivity. This study explored whether the temperament of the mother modulates curiosity, fear, and Hypothalamic-Pituitary-Adrenal (HPA)-axis hormones in different lines of mink. We designed a study with all combinations of cross-mating between males and females from lines of Confident (C) and Fearful (F) mink. The offspring (N = 600) were cross-fostered by C or F mothers until weaning after 1.8 months. Fearfulness and exploration in three behavioral tests plus plasma ACTH and cortisol were measured in the 6-9 months old offspring. Mink of confident parents (line CC) were consistently more curious, the mixed (CF, FC) showed intermediate reactions, and mink of fearful parents (FF) were the least curious and most fearful in all tests. A higher proportion of the offspring was curious when raised by a C foster mother, regardless of the genetic origin (stick test: 45.1% vs. F foster mother: 34.5%). Cortisol was influenced by line of the biological mother, but not by the sire or by the foster mother; offspring of C dams (CC, CF) had consistently lower cortisol concentration (P < .001) than offspring of F dams (FF, FC) in response to acute stress. In conclusion, besides the selection lines (inheritance from both parents) being a major factor determining curiosity/fearfulness of mink, the confident foster mothers increased offspring curiosity. Additionally, we found maternal effects on the HPA-axis, leading to a higher cortisol response to acute stress in adult mink offspring gestated by fearful mothers. The results add to the existing knowledge on maternal influence on offspring development and are particularly relevant for on-farm welfare where selection for low-fear and explorative dams can decrease offspring fearfulness and stress responses.

Proliferation and cell-cell fusion of endometrial carcinoma are induced by the human endogenous retroviral Syncytin-1 and regulated by TGF-beta.

Endometrial carcinomas (EnCa) predominantly represent a steroid hormone-driven tumor initiated from prestages. The human endogenous retrovirus HERV-W envelope gene Syncytin-1 was significantly increased at the mRNA and protein levels in EnCa and prestages compared to controls. Steroid hormone treatment of primary EnCa cells and cell lines induced Syncytin-1 due to a new HERV-W estrogen response element and resulted in increased proliferation. Activation of the cAMP-pathway also resulted in Syncytin-1 upregulation, but in contrast to proliferation, classic cell-cell fusions similar to placental syncytiotrophoblasts occurred. Cell-cell fusions were also histologically identified in endometrioid EnCa tumors in vivo. Clonogenic soft agar experiments showed that Syncytin-1 is also involved in anchorage-independent colony growth as well as in colony fusions depending on steroid hormones or cAMP-activation. The posttranscriptional silencing of Syncytin-1 gene expression and a concomitant functional block of induced cell proliferation and cell-cell fusion with siRNAs proved the essential role of Syncytin-1 in these cellular processes. TGF-beta1 and TGF-beta3 were identified as main regulative factors, due to the finding that steroid hormone inducible TGF-beta1 and TGF-beta3 inhibited cell-cell fusion, whereas antibody-mediated TGF-beta neutralization induced cell-cell fusions. These results showed that induced TGF-beta could override Syncytin-1-mediated cell-cell fusions. Interactions between Syncytin-1 and TGF-beta may contribute to the etiology of EnCa progression and also help to clarify the regulation of cell-cell fusions occurring in development and in other syncytial cell tumors.

The involvement of the intermediate chain of cytoplasmic dynein in binding the motor complex to membranous organelles of Xenopus oocytes.

Cytoplasmic dynein is one of the major motor proteins involved in intracellular transport. It is a protein complex consisting of four subunit classes: heavy chains, intermediate chains (ICs), light intermediate chains, and light chains. In a previous study, we had generated new monoclonal antibodies to the ICs and mapped the ICs to the base of the motor. Because the ICs have been implicated in targeting the motor to cargo, we tested whether these new antibodies to the intermediate chain could block the function of cytoplasmic dynein. When cytoplasmic extracts of Xenopus oocytes were incubated with either one of the monoclonal antibodies (m74-1, m74-2), neither organelle movement nor network formation was observed. Network formation and membrane transport was blocked at an antibody concentration as low as 15 micrograms/ml. In contrast to these observations, no effect was observed on organelle movement and tubular network formation in the presence of a control antibody at concentrations as high as 0.5 mg/ml. After incubating cytoplasmic extracts or isolated membranes with the monoclonal antibodies m74-1 and m74-2, the dynein IC polypeptide was no longer detectable in the membrane fraction by SDS-PAGE immunoblot, indicating a loss of cytoplasmic dynein from the membrane. We used a panel of dynein IC truncation mutants and mapped the epitopes of both antibodies to the N-terminal coiled-coil domain, in close proximity to the p150Glued binding domain. In an IC affinity column binding assay, both antibodies inhibited the IC-p150Glued interaction. Thus these findings demonstrate that direct IC-p150Glued interaction is required for the proper attachment of cytoplasmic dynein to membranes.

Myosin Va bound to phagosomes binds to F-actin and delays microtubule-dependent motility.

We established a light microscopy-based assay that reconstitutes the binding of phagosomes purified from mouse macrophages to preassembled F-actin in vitro. Both endogenous myosin Va from mouse macrophages and exogenous myosin Va from chicken brain stimulated the phagosome-F-actin interaction. Myosin Va association with phagosomes correlated with their ability to bind F-actin in an ATP-regulated manner and antibodies to myosin Va specifically blocked the ATP-sensitive phagosome binding to F-actin. The uptake and retrograde transport of phagosomes from the periphery to the center of cells in bone marrow macrophages was observed in both normal mice and mice homozygous for the dilute-lethal spontaneous mutation (myosin Va null). However, in dilute-lethal macrophages the accumulation of phagosomes in the perinuclear region occurred twofold faster than in normal macrophages. Motion analysis revealed saltatory phagosome movement with temporarily reversed direction in normal macrophages, whereas almost no reversals in direction were observed in dilute-lethal macrophages. These observations demonstrate that myosin Va mediates phagosome binding to F-actin, resulting in a delay in microtubule-dependent retrograde phagosome movement toward the cell center. We propose an "antagonistic/cooperative mechanism" to explain the saltatory phagosome movement toward the cell center in normal macrophages.

Relaxation of plasma waves in Fermi-degenerate quantum plasmas.

Plasma waves in a Fermi-degenerate quantum plasma are studied in the framework of the Vlasov-Poisson self-consistent-field theory. A complete time-dependent analytical solution of the initial-value problem is obtained for a multistream model both by stationary-wave and Laplace-transform methods. In the continuum limit, the excitation spectrum can be expressed by the imaginary part of the response function to the initial perturbations. The relaxation of plasma waves is discussed for one-dimensional systems with both Fermi and Maxwellian statistics. Apart from the usual exponential Landau damping, regimes of sub- and superexponential damping can be identified due to the phase relaxation of single-particle excitations. In addition, beat waves and echoes are discussed.

What you get from what you see: Parametric assessment of visual processing capacity in multiple sclerosis and its relation to cognitive fatigue.

Multiple sclerosis (MS(1)) is a diffusely disseminated inflammatory disease affecting widespread cerebral networks. Major cognitive impairments are a reduction of processing capacity and mental fatigue, i.e., an "abnormal sense of tiredness or lack of energy". Here, the present study provides the first assessment of the distinct components of visual processing capacity based on a 'theory of visual attention' (TVA(2)) in MS patients and relates it to measures of subjective as well as (more) objective fatigue. The performance of 36 relapsing-remitting MS patients in a whole report task of brief letter arrays was compared to healthy control subjects matched for gender, age and education. Additionally, the sustained attention test PASAT-3(3) served as a measure of objective fatigue, and the self-report questionnaire MFIS(4) as a measure of subjective fatigue. Results indicate generally diminished processing speed as well as iconic memory buffers, and increased perceptual thresholds in MS patients compared to healthy controls. Block-wise analysis of attentional parameters shows that the processing speed performance of MS patients declines in the second half of the TVA-based test compared to healthy controls and in particular for patients with high versus low objective fatigue. These findings describe which aspects of processing capacity are impaired in MS, and show that fatigue mainly affects speed of processing. Thus, TVA-based assessment provides a novel approach in the determination of cognitive impairments and fatigue in MS. However, further research is required to elucidate the complex relations of processing capacity and cognitive functions in MS.

GCMB mutation in familial isolated hypoparathyroidism with residual secretion of parathyroid hormone.

Isolated hypoparathyroidism is an uncommon metabolic disorder characterized by hypocalcemia and hyperphosphatemia, with absent or low levels of PTH. It may present as an apparently sporadic disorder or may be transmitted in families as a genetic trait. Mutations of the calcium-sensing receptor gene and of the preproPTH gene have been reported in occasional cases, and a mutation of the parathyroid-specific transcription factor GCMB gene has been reported in one familial case. We report a second family with isolated hypoparathyroidism and a GCMB mutation. The patients were two siblings from asymptomatic, first-cousin parents, indicating autosomal recessive inheritance. The mutation consisted of the substitution of a glycine residue with a serine at position 63 (G63S) in the DNA-binding GCM domain of GCMB. Functional studies in transfected cells showed that the mutation caused loss of GCMB function, as it abolished transactivation capacity, despite normal subcellular localization, protein stability, and DNA-binding specificity. Contrary to the previously reported family, our patients displayed low but clearly detectable levels of PTH in plasma. This residual hormone secretion probably results from a very small residual activity of the G63S mutant GCMB.

Stimulation of GCMa and syncytin via cAMP mediated PKA signaling in human trophoblastic cells under normoxic and hypoxic conditions.

Glial cells missing a (GCMa) belongs to a new transcription factor family. Syncytin was shown to be a target gene of GCMa. Here, we demonstrate that the protein kinase A (PKA) pathway acts upstream of GCMa. After transient transfection of BeWo cells with PKA, GCMa transcriptional activity and both GCMa and syncytin transcripts were upregulated. This increase was accompanied by further cellular differentiation. Using normoxic or hypoxic conditions to mimic pathophysiological settings known to diminish trophoblast differentiation, we found that gene repressive effects of oxygen deficiency were compensated by the induction of the PKA pathway. We propose that GCMa-driven syncytin expression is the key mechanism for syncytiotrophoblast formation.

High intensity, low frequency catheter-delivered ultrasound dissolution of occlusive coronary artery thrombi: an in vitro and in vivo study.

OBJECTIVES: This study assessed the efficacy of a new high intensity, low frequency therapeutic coronary ultrasound catheter for thrombus dissolution in vitro and in vivo in canine coronary arteries. BACKGROUND: Therapeutic ultrasound has been shown to dissolve thrombi in vitro and in peripheral arteries in vivo. There have been no previous studies on in vivo coronary thrombus dissolution by ultrasound. METHODS: In vitro, we exposed 1- to 4-h old human blood clots for 3 min to pulsed-wave ultrasound. Clot dissolution under various conditions was evaluated. In vivo occlusive coronary thrombi were induced in 18 dogs. RESULTS: In vitro irrigation alone (10 ml/min of normal saline solution) and ultrasound alone each contributed to a reduction of clot weight by 47.1 +/- 11.4 mg and 84.6 +/- 25.6 mg, respectively, after 3 min (p < 0.001). Ultrasound plus irrigation resulted in a reduction of clot weight by 216.5 +/- 31.5 mg after 3 min (p < 0.001). The magnitude of clot dissolution was considerably amplified when ultrasound energy was combined with irrigation, probably because of cavitational effects. In vivo, in three dogs mechanical passage of the unactivated probe failed to recanalize the artery, and the arteries remained thrombotically occluded. After passage of the activated ultrasound probe, angiography revealed widely patent coronary arteries in 13 of 15 dogs and partial recanalization with filling defects indicative of residual thrombus in 2 of 15 dogs. Three of 15 coronary arteries were histologically free of residual thrombi. Mural thrombi extending to < or = 10% of the vessel circumference were seen in 10 of 15 dogs. Residual thrombi > or = 50% of the vessel circumference were found in two cases. There was no histologic evidence of ultrasound-mediated vessel damage. CONCLUSIONS: Catheter-delivered therapeutic ultrasound effectively dissolves clots in vitro and in canine coronary arteries in vivo. Thus, therapeutic catheter-delivered ultrasound has the potential to serve as an adjunct or alternative treatment for thrombus-mediated coronary ischemic syndromes or myocardial infarction.

Sustainable Capture: Concepts for Managing Stream-Aquifer Systems.

Most surface water bodies (i.e., streams, lakes, etc.) are connected to the groundwater system to some degree so that changes to surface water bodies (either diversions or importations) can change flows in aquifer systems, and pumping from an aquifer can reduce discharge to, or induce additional recharge from streams, springs, and lakes. The timescales of these interactions are often very long (decades), making sustainable management of these systems difficult if relying only on observations of system responses. Instead, management scenarios are often analyzed based on numerical modeling. In this paper we propose a framework and metrics that can be used to relate the Theis concepts of capture to sustainable measures of stream-aquifer systems. We introduce four concepts: Sustainable Capture Fractions, Sustainable Capture Thresholds, Capture Efficiency, and Sustainable Groundwater Storage that can be used as the basis for developing metrics for sustainable management of stream-aquifer systems. We demonstrate their utility on a hypothetical stream-aquifer system where pumping captures both streamflow and discharge to phreatophytes at different amounts based on pumping location. In particular, Capture Efficiency (CE) can be easily understood by both scientists and non-scientist alike, and readily identifies vulnerabilities to sustainable stream-aquifer management when its value exceeds 100%.

Immunostaining of spindle components in tipulid spermatocytes using a serum against pericentriolar material.

First meiotic division of tipulid (Pales ferruginea) spermatocytes was investigated by double immunostaining with anti-tubulin IgG and scleroderma 5051 serum against pericentriolar material (PCM). PCM-like material became visible in late diakinesis in centrosomal areas as well as in kinetochores. Anti-PCM fluorescence was most pronounced in metaphase and diminished again in anaphase. Displacement of one of the centrosomes from the nucleus at diakinesis in Pales spermatocytes leads to the formation of a bipolar, normally functioning spindle possessing one aster and centriole-free spindle pole (AFP). In about 80% of the AFPs observed there were no traces of anti-PCM staining detectable. This finding supports the assumption based on previous studies that polar PCM is not obligatory for spindle pole formation. The chromosomes seem to be able to induce the organization of a half-spindle. The strong anti-PCM fluorescence of the kinetochores observed here may be taken as further indication of tipulid chromosome autonomy regarding spindle formation.

Intravascular therapeutic ultrasound thrombolysis in acute myocardial infarctions.

Catheter-delivered, therapeutic ultrasound was shown to effectively dissolve thrombus in vitro and in vivo. This first study in 14 patients with acute myocardial infarctions demonstrates that it is a safe and effective treatment alternative that deserves further clinical evaluation.

Global and regional modelling of Arctic-boreal vegetation distribution and its sensitivity to altered forcing.

Understanding the distribution and function of Arctic and boreal ecosystems under current conditions and their vulnerability to altered forcing is crucial to our assessment of future global environmental change. Such efforts can be facilitated by the development and application of ecological models that simulate realistic patterns of vegetation change at high latitudes. This paper reviews three classes of ecological models that have been implemented to extrapolate vegetation information in space (e.g. across the Arctic and adjacent domains) and over historical and future periods (e.g. under altered climate and other forcings). These are: (i) equilibrium biogeographical models; (ii) frame-based transient ecosystem models, and (iii) dynamic global vegetation models (DGVMs). The equilibrium response of high-latitude vegetation to scenarios of increased surface air temperatures projected by equilibrium biogeographical models is for tundra to be replaced by a northward shift of boreal woodland and forests. A frame-based model (ALFRESCO) indicates the same directional changes, but illustrates how response time depends on rate of temperature increase and concomitant changes in moisture regime and fire disturbance return period. Key disadvantages of the equilibrium models are that they do not simulate time-dependent responses of vegetation and the role of disturbance is omitted or highly generalized. Disadvantages of the frame-based models are that vegetation type is modelled as a set unit as opposed to an association of individually simulated plant functional types and that the role of ecosystem biogeochemistry in succession is not explicitly considered. DGVMs explicitly model disturbance (e.g. fire), operate on plant functional types, and incorporate constraints of nutrient availability on biomass production in the simulation of vegetation dynamics. Under changing climate, DGVMs detail conversion of tundra to tree-dominated boreal landscapes along with time-dependent responses of biomass, net primary production, and soil organic matter turnover--which all increase with warming. Key improvements to DGVMs that are needed to portray behaviour of arctic and boreal ecosystems adequately are the inclusion of anaerobic soil processes for inundated landscapes, permafrost dynamics, and moss-lichen layer biogeochemistry, as well as broader explicit accounting of disturbance regimes (including insect outbreaks and land management). Transient simulation of these landscapes can be further tailored to high-latitude processes and issues by spatially interactive, gridded application of arctic/boreal frame-based models and development of dynamic regional vegetation models (DRVMs) utilizing plant functional type schemes that capture the variety of high-latitude environments.

Acoustic excitations in suspensions of soft colloids

Vibrational modes in suspensions of soft colloids in a fluid can be detected experimentally by Brillouin light scattering. Besides the usual acoustic mode, being essentially the longitudinal phonon of the liquid matrix, an "opticlike" mode is observed in giant starlike micelles at low volume fractions. We propose that this opticlike mode is due mainly to the internal vibration of each hairy particle.