The TORCH PMT: a close packing, multi-anode, long life MCP-PMT for Cherenkov applications

Photek (U.K.) and the TORCH collaboration are undertaking a three year development program to produce a novel square MCP-PMT for single photon detection. The TORCH detector aims to provide particle identification in the 2–10 GeV/c momentum range, using a Time-of-Flight method based on Cherenkov light. It is a stand-alone R&D project with possible application in LHCb, and has been proposed for the LHCb Upgrade. The Microchannel Plate (MCP) detector will provide a single photon timing accuracy of 40 ps, and its development will include the following properties: (i) Long lifetime up to at least 5 C/cm2; (ii) Multi-anode output with a spatial resolution of 6 mm and 0.4 mm respectively in the horizontal and vertical directions, incorporating a novel charge-sharing technique; (iii) Close packing on two opposing sides with an active area fill factor of 88% in the horizontal direction. Results from simulations modelling the MCP detector performance factoring in the pulse height variation from the detector, NINO threshold levels and potential charge sharing techniques that enhance the position resolution beyond the physical pitch of the pixel layout will be discussed. Also, a novel method of coupling the MCP-PMT output pads using Anisotropic Conductive Film (ACF) will be described. This minimises parasitic input capacitance by allowing very close proximity between the frontend electronics and the MCP detector

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Antipsychotics and Identity:The Adverse Effect No One is Talking About

People who take antipsychotics, and people who are prescribed antipsychotics without taking them, experience effects which are not frequently discussed: effects on their identity and sense of self. Qualitative research indicates the relationship between taking APs and identity is multilayered, and changeable. Taking APs can restore people to their earlier, pre-symptom sense of self. Being prescribed and taking APs can also, on the other hand, be experienced as damaging, erasing and dulling people’s sense of who they are. This complexity deserves exploration in clinical practice, which we believe is currently not done routinely. More work is needed to understand whether, and how, the relationship between identity and APs is being addressed. We outline the importance of having discussions in a clinical space around identity, and a sense of agency, on the grounds that true recovery-oriented care, which enacts shared decision-making principles, demands it. Further, we argue that it will allow for better therapeutic alliance and trust to be forged between clinician and client, ultimately leading to better care.</p

Minimal, superficial DNA damage in human skin from filtered far-ultraviolet C

Funding: This study was funded in part by MR/P012248/1 to R.P.H. from the Medical Research Council.Publisher PDFPeer reviewe

A longitudinal study of DNA methylation as a potential mediator of age-related diabetes risk

DNA methylation (DNAm) has been found to show robust and widespread age-related changes across the genome. DNAm profiles from whole blood can be used to predict human aging rates with great accuracy. We sought to test whether DNAm-based predictions of age are related to phenotypes associated with type 2 diabetes (T2D), with the goal of identifying risk factors potentially mediated by DNAm. Our participants were 43 women enrolled in the Women's Health Initiative. We obtained methylation data via the Illumina 450K Methylation array on whole blood samples from participants at three timepoints, covering on average 16 years per participant. We employed the method and software of Horvath, which uses DNAm at 353 CpGs to form a DNAm-based estimate of chronological age. We then calculated the epigenetic age acceleration, or Δage, at each timepoint. We fit linear mixed models to characterize how Δage contributed to a longitudinal model of aging and diabetes-related phenotypes and risk factors. For most participants, Δage remained constant, indicating that age acceleration is generally stable over time. We found that Δage associated with body mass index (p = 0.0012), waist circumference (p = 0.033), and fasting glucose (p = 0.0073), with the relationship with BMI maintaining significance after correction for multiple testing. Replication in a larger cohort of 157 WHI participants spanning 3 years was unsuccessful, possibly due to the shorter time frame covered. Our results suggest that DNAm has the potential to act as a mediator between aging and diabetes-related phenotypes, or alternatively, may serve as a biomarker of these phenotypes

Analyzing who is relevant to engage in environmental decision-making processes by interests, influence and impact:The 3i framework

Outcomes in participatory environmental processes are strongly affected by choices about who is engaged. Inclusive engagement diversifies the range of interests and perspectives represented, including those from vulnerable and marginalized groups, ultimately contributing to more socially and environmentally sustainable and equitable outcomes. However, existing “stakeholder analysis” methods often bias participant identification away from disenfranchised groups with limited pre-existing interest or influence, instead favoring the most easily accessed and influential stakeholders. This paper draws on research impact theory and practice to propose a new, more inclusive approach, adding impact to the existing interest and influence criteria (which each begin with the letter “i", hence the 3i framework) that are typically used to identify, categorize and prioritize those who are relevant to be included or excluded from engagement processes. As part of this proposed 3i analysis approach, we articulate a new typology of relevant parties to engage in environmental decision-making processes, including: uninterested; uninterested and impacted; uninterested influencers; disinterested, influential and impacted; only interested; interested and impacted; interested influencers; and interested, influential and impacted. Except for the first group, all types of relevant parties should be considered for engagement wherever possible, with participation strategies tailored to their specific 3i profile. The approach was developed and refined through a series of workshops before developing it into a survey instrument that was piloted to gather 3i data efficiently across several national contexts. Survey findings are presented for a case study identifying those relevant to wetland and peatland restoration in a Scottish catchment. If widely adopted, the 3i framework would be the most consequential change in stakeholder analysis methods since the introduction of interest-influence matrices in the 1980s.</p

Analyzing who is relevant to engage in environmental decision-making processes by interests, influence and impact: The 3i framework

\ua9 2024 The AuthorsOutcomes in participatory environmental processes are strongly affected by choices about who is engaged. Inclusive engagement diversifies the range of interests and perspectives represented, including those from vulnerable and marginalized groups, ultimately contributing to more socially and environmentally sustainable and equitable outcomes. However, existing “stakeholder analysis” methods often bias participant identification away from disenfranchised groups with limited pre-existing interest or influence, instead favoring the most easily accessed and influential stakeholders. This paper draws on research impact theory and practice to propose a new, more inclusive approach, adding impact to the existing interest and influence criteria (which each begin with the letter “i", hence the 3i framework) that are typically used to identify, categorize and prioritize those who are relevant to be included or excluded from engagement processes. As part of this proposed 3i analysis approach, we articulate a new typology of relevant parties to engage in environmental decision-making processes, including: uninterested; uninterested and impacted; uninterested influencers; disinterested, influential and impacted; only interested; interested and impacted; interested influencers; and interested, influential and impacted. Except for the first group, all types of relevant parties should be considered for engagement wherever possible, with participation strategies tailored to their specific 3i profile. The approach was developed and refined through a series of workshops before developing it into a survey instrument that was piloted to gather 3i data efficiently across several national contexts. Survey findings are presented for a case study identifying those relevant to wetland and peatland restoration in a Scottish catchment. If widely adopted, the 3i framework would be the most consequential change in stakeholder analysis methods since the introduction of interest-influence matrices in the 1980s

A proposed mechanism for progesterone regulation of trophoblast MMP2 transcription independent of classical progesterone response elements on its promoter

BACKGROUND: Progesterone receptor act as ligand-inducible transcription factor in the respective target cells by binding to specific progesterone response elements in the promoter of the target genes. However, despite the lack of the classical progesterone response elements on matrix-metalloproteinase-2 promoter, progesterone has been shown to decrease the activity of this promoter PRESENTATION OF THE HYPOTHESIS: It has recently been suggested that in addition to interacting with their classical co-activators and co-repressors, progesterone receptor are capable of binding to several transcription factors. By interacting with other classes of transcription factors, progesterone receptor is capable of transcriptional activation through the transcription factors cognate DNA binding site. TESTING THE HYPOTHESIS: Exploring transcription factors and transcription binding sites, interacting with the progesterone receptor in modulation of the matrix-metalloproteinase promoter. IMPLICATIONS OF THE HYPOTHESIS: Identification of additional endogenous progesterone target genes makes it possible to further explore the signaling mechanisms by which the hormone regulates biological actions. Furthermore, the concepts of ligand-driven conformational diversity and selective tissue actions can be exploited in the future for drug development which selectively regulate orphan receptors from the nuclear receptor family

TORCH: A large area time-of-flight detector for particle identification

TORCH is a time-of-flight detector that is being developed for the Upgrade II of the LHCb experiment, with the aim of providing charged particle identification over the momentum range 2–10 GeV/. A small-scale TORCH demonstrator with customised readout electronics has been operated successfully in beam tests at the CERN PS. Preliminary results indicate that a single-photon resolution better than 100 ps can be achieved