Transverse modulational dynamics of quenched patterns.

We study the modulational dynamics of striped patterns formed in the wake of a planar directional quench. Such quenches, which move across a medium and nucleate pattern-forming instabilities in their wake, have been shown in numerous applications to control and select the wavenumber and orientation of striped phases. In the context of the prototypical complex Ginzburg-Landau and Swift-Hohenberg equations, we use a multiple-scale analysis to derive a one-dimensional viscous Burgers' equation, which describes the long-wavelength modulational and defect dynamics in the direction transverse to the quenching motion, that is, along the quenching line. We show that the wavenumber selecting properties of the quench determine the nonlinear flux parameter in the Burgers' modulation equation, while the viscosity parameter of the Burgers' equation is naturally determined by the transverse diffusivity of the pure stripe state. We use this approximation to accurately characterize the transverse dynamics of several types of defects formed in the wake, including grain boundaries and phase-slips.

Sequential rupture of two concomitant cerebral aneurysms.

The diagnosis of multiple cerebral aneurysms in patients with a spontaneous aneurysmal subarachnoid haemorrhage is not uncommon. The incidence of rupture from a second aneurysm, whilst the patient is recovering from a first bleed is however extremely rare. We report a 21-year-old female with a WFNS grade 1 subarachnoid haemorrhage secondary to a ruptured 5mm right posterior communicating artery aneurysm which was secured with clipping. Sixteen days later, whilst an in-patient, she suffered a second SAH from a left anterior choroidal artery aneurysm which was subsequently coiled. Comparison of digital subtraction angiography showed an almost doubling of the aneurysm from 2.7x2 mm to 4.4x2.3 mm. We review the literature of previously reported simultaneous and sequential aneurysmal subarachnoid haemorrhage and add to the sparse literature on this rare phenomena.

Obstacles for T-lymphocytes in the tumour microenvironment: Therapeutic challenges, advances and opportunities beyond immune checkpoint.

The tumour microenvironment (TME) imposes a major obstacle to infiltrating T-lymphocytes and suppresses their function. Several immune checkpoint proteins that interfere with ligand/receptor interactions and impede T-cell anti-tumour responses have been identified. Immunotherapies that block immune checkpoints have revolutionized the treatment paradigm for many patients with advanced-stage tumours. However, metabolic constraints and soluble factors that exist within the TME exacerbate the functional exhaustion of tumour-infiltrating T-cells. Here we review these multifactorial constraints and mechanisms - elevated immunosuppressive metabolites and enzymes, nutrient insufficiency, hypoxia, increased acidity, immense amounts of extracellular ATP and adenosine, dysregulated bioenergetic and purinergic signalling, and ionic imbalance - that operate in the TME and collectively suppress T-cell function. We discuss how scientific advances could help overcome the complex TME obstacles for tumour-infiltrating T-lymphocytes, aiming to stimulate further research for developing new therapeutic strategies by harnessing the full potential of the immune system in combating cancer.

Subtarsal Versus Transconjunctival Approach: A Long-Term Follow-Up of Esthetic Outcomes and Complications.

PURPOSE: There is limited data that compares the long-term esthetic outcomes in patients who undergo traumatic orbital reconstruction with the subtarsal (STA) and transconjunctival approaches. The purpose of this study is to determine the long-term differences in scarring, cosmesis, and complications between the 2 approaches. MATERIALS AND METHODS: Sixty-seven patients were examined on average 39 months after surgery. Each patient was evaluated for satisfaction in surgical scarring and complications including diplopia, nerve paresthesia, lid malposition, and epiphora. Photographic images of each patient were reviewed by 3 experienced maxillofacial surgeons and 3 nonmedical personnel to determine if scarring was present and quantify it using the Manchester scar scale (MSS). Scarring was then compared using 3 different objective scales; MSS, modified Vancouver scar scale and the modified Stony Brook scar evaluation scale. Recorded data were analyzed using the χ2 test and Fisher exact test to determine statistical significance (P < .05). RESULTS: No visible scar formation was seen in 61 to 76.5% of patients who had an STA using either of the 3 scales, although the MSS proved to be significantly more accurate when assessing linear periorbital scars than the modified Vancouver scar scale and Stony Brook scar evaluation scale (P < .001). Surgeons were able to correctly identify subtarsal scars in 26.3% of patients, in comparison with the nonmedically trained people identifying just 10.6% of scars. Most of these showed only mild scar formation and are unlikely to have any significant effect on patient's quality-of-life. Overall, 93.3% of patients who had an STA were satisfied with the scar formation. CONCLUSIONS: While the transconjunctival approach is a useful technique that offers a surgical approach with no scarring, over the long-term, only a small proportion of STA scars are visible to the average person. Surgeons should consider both approaches and their clinical advantages when treating patients with traumatic orbital injuries.

Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids.

During gastrulation, the pluripotent epiblast self-organizes into the 3 germ layers-endoderm, mesoderm and ectoderm, which eventually form the entire embryo. Decades of research in the mouse embryo have revealed that a signaling cascade involving the Bone Morphogenic Protein (BMP), WNT, and NODAL pathways is necessary for gastrulation. In vivo, WNT and NODAL ligands are expressed near the site of gastrulation in the posterior of the embryo, and knockout of these ligands leads to a failure to gastrulate. These data have led to the prevailing view that a signaling gradient in WNT and NODAL underlies patterning during gastrulation; however, the activities of these pathways in space and time have never been directly observed. In this study, we quantify BMP, WNT, and NODAL signaling dynamics in an in vitro model of human gastrulation. Our data suggest that BMP signaling initiates waves of WNT and NODAL signaling activity that move toward the colony center at a constant rate. Using a simple mathematical model, we show that this wave-like behavior is inconsistent with a reaction-diffusion-based Turing system, indicating that there is no stable signaling gradient of WNT/NODAL. Instead, the final signaling state is homogeneous, and spatial differences arise only from boundary effects. We further show that the durations of WNT and NODAL signaling control mesoderm differentiation, while the duration of BMP signaling controls differentiation of CDX2-positive extra-embryonic cells. The identity of these extra-embryonic cells has been controversial, and we use RNA sequencing (RNA-seq) to obtain their transcriptomes and show that they closely resemble human trophoblast cells in vivo. The domain of BMP signaling is identical to the domain of differentiation of these trophoblast-like cells; however, neither WNT nor NODAL forms a spatial pattern that maps directly to the mesodermal region, suggesting that mesoderm differentiation is controlled dynamically by the combinatorial effect of multiple signals. We synthesize our data into a mathematical model that accurately recapitulates signaling dynamics and predicts cell fate patterning upon chemical and physical perturbations. Taken together, our study shows that the dynamics of signaling events in the BMP, WNT, and NODAL cascade in the absence of a stable signaling gradient control fate patterning of human gastruloids.

Perineal tears - A review

BACKGROUND: The female perineum is the diamond-shaped inferior outlet of the pelvis. This structure is at risk of trauma during labour because of spontaneous perineal tears of varying degrees or iatrogenic episiotomies. These injuries can result in disabling immediate and long-term complications in the woman. OBJECTIVE: The aim of this article is to provide general practitioners (GPs) with a good understanding of perineal tears by discussing the different classifications, immediate and long-term management, and recommendations for future deliveries. DISCUSSION: Although the majority of perineal tears are managed by obstetricians and gynaecologists, it is important for GPs to understand their management in the event that a patient presents to general practice with concerns during the antenatal or postpartum period.

Universal wave-number selection laws in apical growth.

We study pattern-forming dissipative systems in growing domains. We characterize classes of boundary conditions that allow for defect-free growth and derive universal scaling laws for the wave number in the bulk of the domain. Scalings are based on a description of striped patterns in semibounded domains via strain-displacement relations. We compare predictions with direct simulations in the Swift-Hohenberg, the complex Ginzburg-Landau, the Cahn-Hilliard, and reaction-diffusion equations.

Management of dental infections by medical practitioners.

BACKGROUND: Patients with dental infections frequently present to primary care practitioners such as emergency physicians or general practitioners. It is important for these healthcare professionals to understand how to assess and treat such conditions, including when to refer and to whom. OBJECTIVE: This article aims to cover basic principles of managing patients with dental infections who present to emergency departments or general practice surgeries. DISCUSSION: Maxillofacial surgeons frequently see serious cases of facial and neck infections that can easily be prevented if appropriately managed early.