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.

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.

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.

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.

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.

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.

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%.

Benefits of a ball and chain: simple environmental enrichments improve welfare and reproductive success in farmed American mink (Neovison vison).

Can simple enrichments enhance caged mink welfare? Pilot data from 756 sub-adults spanning three colour-types (strains) identified potentially practical enrichments, and suggested beneficial effects on temperament and fur-chewing. Our main experiment started with 2032 Black mink on three farms: from each of 508 families, one juvenile male-female pair was enriched (E) with two balls and a hanging plastic chain or length of hose, while a second pair was left as a non-enriched (NE) control. At 8 months, more than half the subjects were killed for pelts, and 302 new females were recruited (half enriched: 'late E'). Several signs of improved welfare or productivity emerged. Access to enrichment increased play in juveniles. E mink were calmer (less aggressive in temperament tests; quieter when handled; less fearful, if male), and less likely to fur-chew, although other stereotypic behaviours were not reduced. On one farm, E females had lower cortisol (inferred from faecal metabolites). E males tended to copulate for longer. E females also weaned more offspring: about 10% more juveniles per E female, primarily caused by reduced rates of barrenness ('late E' females also giving birth to bigger litters on one farm), effects that our data cautiously suggest were partly mediated by reduced inactivity and changes in temperament. Pelt quality seemed unaffected, but E animals had cleaner cages. In a subsidiary side-study using 368 mink of a second colour-type ('Demis'), similar temperament effects emerged, and while E did not reduce fur-chewing or improve reproductive success in this colour-type, E animals were judged to have better pelts. Overall, simple enrichments were thus beneficial. These findings should encourage welfare improvements on fur farms (which house 60-70 million mink p.a.) and in breeding centres where endangered mustelids (e.g. black-footed ferrets) often reproduce poorly. They should also stimulate future research into more effective practical enrichments.

Evaluation of MODFLOW-LGR in connection with a synthetic regional-scale model.

This work studies costs and benefits of utilizing local-grid refinement (LGR) as implemented in MODFLOW-LGR to simulate groundwater flow in a buried tunnel valley interacting with a regional aquifer. Two alternative LGR methods were used: the shared-node (SN) method and the ghost-node (GN) method. To conserve flows the SN method requires correction of sources and sinks in cells at the refined/coarse-grid interface. We found that the optimal correction method is case dependent and difficult to identify in practice. However, the results showed little difference and suggest that identifying the optimal method was of minor importance in our case. The GN method does not require corrections at the models' interface, and it uses a simpler head interpolation scheme than the SN method. The simpler scheme is faster but less accurate so that more iterations may be necessary. However, the GN method solved our flow problem more efficiently than the SN method. The MODFLOW-LGR results were compared with the results obtained using a globally coarse (GC) grid. The LGR simulations required one to two orders of magnitude longer run times than the GC model. However, the improvements of the numerical resolution around the buried valley substantially increased the accuracy of simulated heads and flows compared with the GC simulation. Accuracy further increased locally around the valley flanks when improving the geological resolution using the refined grid. Finally, comparing MODFLOW-LGR simulation with a globally refined (GR) grid showed that the refinement proportion of the model should not exceed 10% to 15% in order to secure method efficiency.

Examination of transcript amounts and activity of protein kinase CK2 in muscle lysates of different types of human muscle pathologies.

Motoneurons release the heparansulfate proteoglycan agrin and thereby activate the muscle-specific receptor tyrosine kinase (MuSK), which is the main organizer of subsynaptic specializations at the neuromuscular junction. Recently, we showed that (1) the protein kinase CK2 interacts with the intracellular region of MuSK; (2) the CK2 protein is enriched and co-localized with MuSK at postsynaptic specializations; (3) CK2-mediated phosphorylation of serine residues within a specific MuSK epitope, named the kinase insert, regulates acetylcholine receptor (AChR) clustering; (4) muscle-specific CK2beta knockout mice develop a myasthenic phenotype due to impaired muscle endplate structure and function (see Genes Dev 20(13):1800-1816, 2006). Here, we investigated for the first time if CK2 is modulated in biopsies from human patients. To this end, we measured transcript amounts of the subunits CK2alpha and CK2beta and determined holoenzyme CK2 activity in 34 muscle biopsies of human patients with different muscle pathologies.

Hypersonic acoustic excitations in binary colloidal crystals: big versus small hard sphere control.

The phononic band structure of two binary colloidal crystals, at hypersonic frequencies, is studied by means of Brillouin light scattering and analyzed in conjunction with corresponding dispersion diagrams of the single colloidal crystals of the constituent particles. Besides the acoustic band of the average medium, the authors' results show the existence of narrow bands originating from resonant multipole modes of the individual particles as well as Bragg-type modes due to the (short-range) periodicity. Strong interaction, leading to the occurrence of hybridization gaps, is observed between the acoustic band and the band of quadrupole modes of the particles that occupy the largest fractional volume of the mixed crystal; the effective radius is either that of the large (in the symmetric NaCl-type crystalline phase) or the small (in the asymmetric NaZn(13)-type crystalline phase) particles. The possibility to reveal a universal behavior of the phononic band structure for different single and binary colloidal crystalline suspensions, by representing in the dispersion diagrams reduced quantities using an appropriate length scale, is discussed.

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.

A microtubule-based, dynein-dependent force induces local cell protrusions: Implications for neurite initiation.

A key event in neurite initiation is the accumulation of microtubule bundles at the neuron periphery. We hypothesized that such bundled microtubules may generate a force at the plasma membrane that facilitates neurite initiation. To test this idea we observed the behavior of microtubule bundles that were induced by the microtubule-associated protein MAP2c. Endogenous MAP2c contributes to neurite initiation in primary neurons, and exogeneous MAP2c is sufficient to induce neurites in Neuro-2a cells. We performed nocodazol washout experiments in primary neurons, Neuro-2a cells and COS-7 cells to investigate the underlying mechanism. During nocodazol washout, small microtubule bundles formed rapidly in the cytoplasm and immediately began to move toward the cell periphery in a unidirectional manner. In neurons and Neuro-2a cells, neurite-like processes extended within minutes and concurrently accumulated bundles of repolymerized microtubules. Speckle microscopy in COS-7 cells indicated that bundle movement was due to transport, not treadmilling. At the periphery bundles remained under a unidirectional force and induced local cell protrusions that were further enhanced by suppression of Rho kinase activity. Surprisingly, this bundle motility was independent of classical actin- or microtubule-based tracks. It was, however, reversed by function-blocking antibodies against dynein. Suppression of dynein expression in primary neurons by RNA interference severely inhibited the generation of new neurites, but not the elongation of existing neurites formed prior to dynein knockdown. Together, these cell biological data suggest that neuronal microtubule-associated proteins induce microtubule bundles that are pushed outward by dynein and locally override inward contraction to initiate neurite-like cell protrusions. A similar force-generating mechanism might participate in spontaneous initiation of neurites in developing neurons.

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.

Three-dimensional reconstruction of the dynactin complex by single-particle image analysis.

Dynactin is a large complex of at least nine distinct proteins that co-complexes with cytoplasmic dynein within cells, where it plays a major role as a regulator of the motor's function. Owing to its large size and complexity, relatively little is known about dynactin's 3D structure or the structural basis of its function. Use of single-particle image analysis techniques has enabled us to produce the first 3D reconstruction of the dynactin complex, to a resolution of 3 nm. The actin-related protein (Arp) backbone of the filament has been clearly visualized. Fitting of models of the Arp backbone showed that it consists of 10 subunits. Additional mass, not part of the Arp backbone, was also seen. A preliminary fitting of the capping protein CapZ structure into our 3D reconstruction of the dynactin complex suggests that it is optimally placed to perform its proposed function as a stabilizer of the Arp1 backbone and gives clues as to likely interaction points between the capping protein and Arp subunits. The results provide the first detailed visualization of the dynactin complex and shed light on the mode of interaction between several of its constituent proteins and their possible functions.

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.

Structure of amorphous poly-(ethylmethacrylate): a wide-angle x-ray scattering study.

The local, temperature dependent structure of poly-(ethylmethacrylate) was studied with wide-angle x-ray scattering. The results were set into context to recent wide-angle neutron scattering results as well as to the results from a multitude of studies of the dynamics of this polymer. The temperature dependence of the wide angle x-ray results point to the development of local order which is backed by the neutron scattering results and which is connected to characteristic temperatures of the relaxation dynamic T(g) and T(c). The poly-(ethylmethacrylate) was studied in its predominantly syndiotactic as well as predominantly isotactic state displaying vastly different local structures as manifested in the x-ray results.

The spectrum of vibration modes in soft opals.

Numerous vibrational modes of spherical submicrometer particles in fabricated soft opals are experimentally detected by Brillouin light scattering and theoretically identified by their spherical harmonics by means of single-phonon scattering-cross-section calculations. The particle size polydispersity is reflected in the line shape of the low-frequency modes, whereas lattice vibrations are probably responsible for the observed overdamped transverse mode.

Interaction, cooperative promoter modulation, and renal colocalization of GCMa and Pitx2.

The transcription factor GCMa is a member of a new small family of transcription factors with a conserved zinc-containing DNA-binding domain. All members of this transcription factor family play crucial roles as master regulators during development. GCMa is restricted to placenta during development and to kidney and thymus at postnatal stages. It is essential for the formation of the placental labyrinth and as a consequence for survival of the embryo from mid-embryogenesis onwards. Here, we identify Pitx transcription factors as GCMa-interacting proteins. We show that Pitx proteins interact via their conserved homeodomain with the DNA-binding domain of GCMa. As a consequence, Pitx proteins and GCMa exhibit cooperative DNA binding. Furthermore, Pitx proteins influence GCMa-dependent promoter activation in a cell-specific manner. One of the three Pitx paralogues in mice, Pitx2, is the predominant Pitx member present in the placenta and colocalizes on the cellular level with GCMa in the kidney. This is the first description of a regulatory cross-talk between a transcription factor of the GCM family and a homeodomain protein.

Slow dynamics of salol: a pressure- and temperature-dependent light scattering study.

We study the slow dynamics of salol by varying both temperature and pressure using photon correlation spectroscopy and pressure-volume-temperature measurements, and compare the behavior of the structural relaxation time with equations derived within the Adam-Gibbs entropy theory and the Cohen-Grest free volume theory. We find that pressure-dependent data are crucial to assess the validity of these model equations. Our analysis supports the entropy-based equation, and estimates the configurational entropy of salol at ambient pressure approximately 70% of the excess entropy. Finally, we investigate the evolution of the shape of the structural relaxation process, and find that a time-temperature-pressure superposition principle holds over the range investigated.