Synchronization crossover of polariton condensates in weakly disordered lattices

We demonstrate that the synchronization of a lattice of solid-state condensates when intersite tunneling is switched on depends strongly on the weak local disorder. This finding is vital for implementation of condensate arrays as computation devices. The condensates here are nonlinear bosonic fluids of exciton-polaritons trapped in a weakly disordered Bose-Hubbard potential, where the nearest-neighboring tunneling rate (Josephson coupling) can be dynamically tuned. The system can thus be tuned from a localized to a delocalized fluid as the number density or the Josephson coupling between nearest neighbors increases. The localized fluid is observed as a lattice of unsynchronized condensates emitting at different energies set by the disorder potential. In the delocalized phase, the condensates synchronize and long-range order appears, evidenced by narrowing of momentum and energy distributions, new diffraction peaks in momentum space, and spatial coherence between condensates. Our paper identifies similarities and differences of this nonequilibrium crossover to the traditional Bose-glass to superfluid transition in atomic condensates

ImmunoCluster provides a computational framework for the non-specialist to profile high- dimensional cytometry data

High dimensional cytometry is an innovative tool for immune monitoring in health and disease, it has provided novel insight into the underlying biology as well as biomarkers for a variety of diseases. However, the analysis of large multiparametric datasets usually requires specialist computational knowledge. Here we describe ImmunoCluster (https://github.com/kordastilab/ImmunoCluster) an R package for immune profiling cellular heterogeneity in high dimensional liquid and imaging mass cytometry, and flow cytometry data, designed to facilitate computational analysis by a non-specialist. The analysis framework implemented within ImmunoCluster is readily scalable to millions of cells and provides a variety of visualization and analytical approaches, as well as a rich array of plotting tools that can be tailored to users' needs. The protocol consists of three core computational stages: 1, data import and quality control; 2, dimensionality reduction and unsupervised clustering; and 3, annotation and differential testing, all contained within an R-based open-source framework

A core outcome set for localised prostate cancer effectiveness trials

$\textbf{OBJECTIVE}$: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio; which is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. $\textbf{PATIENTS, SUBJECTS AND METHODS}$: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 patients with prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs; cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and eight patients. $\textbf{RESULTS}$: The final COS included 19 outcomes. In all, 12 apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, and sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side-effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. $\textbf{CONCLUSION}$: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions that should be measured in all localised prostate cancer effectiveness trials

Expert Opinion on Laparoscopic Surgery for Colorectal Cancer Parallels Evidence from a Cumulative Meta-Analysis of Randomized Controlled Trials

PMID: 22532846 [PubMed - indexed for MEDLINE] PMCID: PMC3332109 Free PMC ArticlePeer reviewedPublisher PD

Rad21-Cohesin Haploinsufficiency Impedes DNA Repair and Enhances Gastrointestinal Radiosensitivity in Mice

Approximately half of cancer-affected patients receive radiotherapy (RT). The doses delivered have been determined upon empirical experience based upon average radiation responses. Ideally higher curative radiation doses might be employed in patients with genuinely normal radiation responses and importantly radiation hypersensitive patients would be spared the consequences of excessive tissue damage if they were indentified before treatment. Rad21 is an integral subunit of the cohesin complex, which regulates chromosome segregation and DNA damage responses in eukaryotes. We show here, by targeted inactivation of this key cohesin component in mice, that Rad21 is a DNA-damage response gene that markedly affects animal and cell survival. Biallelic deletion of Rad21 results in early embryonic death. Rad21 heterozygous mutant cells are defective in homologous recombination (HR)-mediated gene targeting and sister chromatid exchanges. Rad21+/− animals exhibited sensitivity considerably greater than control littermates when challenged with whole body irradiation (WBI). Importantly, Rad21+/− animals are significantly more sensitive to WBI than Atm heterozygous mutant mice. Since supralethal WBI of mammals most typically leads to death via damage to the gastrointestinal tract (GIT) or the haematopoietic system, we determined the functional status of these organs in the irradiated animals. We found evidence for GIT hypersensitivity of the Rad21 mutants and impaired bone marrow stem cell clonogenic regeneration. These data indicate that Rad21 gene dosage is critical for the ionising radiation (IR) response. Rad21 mutant mice thus represent a new mammalian model for understanding the molecular basis of irradiation effects on normal tissues and have important implications in the understanding of acute radiation toxicity in normal tissues

Bone marrow stromal cells attenuate sepsis via prostaglandin E2— dependent reprogramming of host macrophages to increase their interleukin-10 production

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs—also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/ or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-α) reprogram macrophages by releasing prostaglandin E2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.Sepsis, a serious medical condition that affects 18 million people per year worldwide, is characterized by a generalized inflammatory state caused by infection. Widespread activation of inflammation and coagulation pathways progresses to multiple organ dysfunction, collapse of the circulatory system (septic shock) and death. Because as many people die of sepsis annually as from acute myocardial infarction1, a new treatment regimen is desperately needed. In the last few years, it has been discovered that BMSCs are potent modulators of immune responses2-5. We wondered whether such cells could bring the immune response back into balance, thus attenuating the underlying pathophysiology that eventually leads to severe sepsis, septic shock and death6,7. As a model of sepsis, we chose cecal ligation and puncture (CLP), a procedure that has been used for more than two decades8. This mouse model closely resembles the human disease: it has a focal origin (cecum), is caused by multiple intestinal organisms, and results in septicemia with release of bacterial toxins into the circulation. With no treatment, the majority of the mice die 24-48 h postoperatively. Originally published Nature Medicine, Vol. 15, No. 1, Jan 200