Soft OR and practice : the contribution of the founders of Operation Research

This paper explores the work of some 43 founders of operations research. In particular, it considers the links between soft operations research (OR) and these founders. Several of the founders were direct influencers of the soft OR proponents, whereas others related to the context, process, and content of soft OR. Coupled with the deductive and inductive reasoning approaches of soft OR, it is argued that soft OR is a legitimate branch of OR. The paper also focuses on the embeddedness of the founders, and the soft OR proponents, in practice and argues that, for academics, engagement with practice has been and will continue to be an important driver for the health and development of operations research

Selective phosphodiesterase inhibitors: a promising target for cognition enhancement

# The Author(s) 2008. This article is published with open access at Springerlink.com Rationale One of the major complaints most people face during aging is an impairment in cognitive functioning. This has a negative impact on the quality of daily life and is even more prominent in patients suffering from neurodegenerative and psychiatric disorders including Alzheimer’s disease, schizophrenia, and depression. So far, the majority of cognition enhancers are generally targeting one particular neurotransmitter system. However, recently phosphodiesterases (PDEs) have gained increased attention as a potential new target for cognition enhancement. Inhibition of PDEs increases the intracellular availability of the second messengers cGMP and/or cAMP. Objective The aim of this review was to provide an overvie

Global Patterns and Controls of Nutrient Immobilization On Decomposing Cellulose In Riverine Ecosystems

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature

Patient priorities for fulfilling the principle of respect in research: findings from a modified Delphi study

Abstract Background Standard interpretations of the ethical principle of respect for persons have not incorporated the views and values of patients, especially patients from groups underrepresented in research. This limits the ability of research ethics scholarship, guidance, and oversight to support inclusive, patient-centered research. This study aimed to identify the practical approaches that patients in community-based settings value most for conveying respect in genomics research. Methods We conducted a 3-round, web-based survey using the modified Delphi technique to identify areas of agreement among English-speaking patients at primary care clinics in Washington State and Idaho who had a personal or family history of cancer. In Round 1, respondents rated the importance of 17 items, identified in prior qualitative work, for feeling respected. In Round 2, respondents re-rated each item after reviewing overall group ratings. In Round 3, respondents ranked a subset of the 8 most highly rated items. We calculated each item’s mean and median rankings in Round 3 to identify which approaches were most important for feeling respected in research. Results Forty-one patients consented to the survey, 21 (51%) completed Round 1, and 18 (86% of Round 1) completed each of Rounds 2 and 3. Two sets of rankings were excluded from analysis as speed of response suggested they had not completed the Round 3 ranking task. Respondents prioritized provision of study information to support decision-making (mean ranking 2.6 out of 8; median ranking 1.5) and interactions with research staff characterized by kindness, patience, and a lack of judgment (mean ranking 2.8; median ranking 2) as the most important approaches for conveying respect. Conclusions Informed consent and interpersonal interactions are key ways that research participants experience respect. These can be supported by other approaches to respecting participants, especially when consent and/or direct interactions are infeasible. Future work should continue to engage with patients in community-based settings to identify best practices for research without consent and examine unique perspectives across clinical and demographic groups in different types of research

Additional file 1 of Patient priorities for fulfilling the principle of respect in research: findings from a modified Delphi study

Additional file 1:  Supplemental Material. Survey instruments, Rounds 1-3 (English) and Round 1 (Spanish)

A Randomized Study Comparing the Incidence of Postoperative Pain After Phrenic Nerve Infiltration Vs Nonphrenic Nerve Infiltration During Thoracotomy.

Contains fulltext : 215252.pdf (publisher's version ) (Closed access)Thoracotomy is a common surgical procedure performed worldwide for lung disease. Despite major advances in analgesia, patients still experience severe shoulder, central back and surgical incision site pain in the postoperative period. This study aimed to assess whether intraoperative phrenic nerve infiltration reduces the incidence of postoperative pain and improves peak flow volume measurements during incentive spirometry. 90 patients undergoing open lobectomy were randomly assigned to have phrenic nerve infiltration (n=46) or not (n=44). The phrenic nerve infiltration group received 10 mL of 0.25% bupivacaine into the periphrenic fat pad. Preoperative assessments of spirometry and pain scores were recorded (at rest and with movement). Postoperative assessments included peak flow and pain measurements at intervals up to 72 hours. Less shoulder pain was experienced with phrenic nerve infiltration up to 6 hours postsurgery at rest (P = 0.005) and up to 12 hours with movement (P < 0.001). Reduced back pain was reported in the phrenic nerve infiltration group up to 6 hours after surgery both at rest (P = 0.001) and with movement (P = 0.00). Phrenic nerve infiltration reduced pain at the incision site for up to 3 hours both at rest (P < 0.001) and with movement (P = 0.001). Spirometry readings dropped in both groups with consistently lower readings at baseline and follow-up in the PNI group (P=0.007). Lower analgesic usage of patient controlled analgesia morphine (P < 0.0001), epipleural bupivacaine (P=0.001), and oramorph/zomorph (P=0.0002) were recorded. Our findings indicate that the use of phrenic nerve infiltration significantly reduced patient pain scores during the early postoperative period, particularly during movement. We believe that each technique has advantages and disadvantages; however, further studies with large sample size are warranted

Precise T cell recognition programs designed by transcriptionally linking multiple receptors.

Living cells often identify their correct partner or target cells by integrating information from multiple receptors, achieving levels of recognition that are difficult to obtain with individual molecular interactions. In this study, we engineered a diverse library of multireceptor cell-cell recognition circuits by using synthetic Notch receptors to transcriptionally interconnect multiple molecular recognition events. These synthetic circuits allow engineered T cells to integrate extra- and intracellular antigen recognition, are robust to heterogeneity, and achieve precise recognition by integrating up to three different antigens with positive or negative logic. A three-antigen AND gate composed of three sequentially linked receptors shows selectivity in vivo, clearing three-antigen tumors while ignoring related two-antigen tumors. Daisy-chaining multiple molecular recognition events together in synthetic circuits provides a powerful way to engineer cellular-level recognition

Emergence of a High-Plasticity Cell State during Lung Cancer Evolution.

Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma. The diversity of transcriptional states increases over time and is reproducible across tumors and mice. Cancer cells progressively adopt alternate lineage identities, computationally predicted to be mediated through a common transitional, high-plasticity cell state (HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and human patient-derived xenografts display high capacity for differentiation and proliferation. The HPCS program is associated with poor survival across human cancers and demonstrates chemoresistance in mice. Our study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS.This work was supported by the Transcend Program and Janssen Pharmaceuticals, the Howard Hughes Medical Institute, and, in part, by the NIH/NCI Cancer Center Support Grants P30-CA08748 (MSKCC) and P30-CA14051 (Koch Institute). T.T. is supported by American Cancer Society, Rita Allen, Josie Robertson Scholar, and V Foundation Scholarships and the American Association for Cancer Research Next Generation Transformative Research Award; the American Lung Association; the Stanley and Fiona Druckenmiller Center for Lung Cancer Research; and NCI-CA187317. T.J. is supported by NCI-PO1CA42063. A.R. is supported by the Klarman Cell Observatory. J.E.C is supported by the MSK T32 Investigational Cancer Therapeutics Training Program Grant (NIH MSK ICTTP T32-CA009207). P.P.M. is supported by NCI-CA196405. L.M. is supported by The Alan and Sandra Gerry Foundation. We acknowledge the use of the Integrated Genomics Operation Core, funded by CCSG P30-CA08748, Cycle for Survival, and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology at MSKCC; the Flow Cytometry and Histology Core Facilities at the Swanson Biotechnology Center at the Koch Institute; and the MIT Bio-Micro Center. A.R., T.J.and A.A. are Howard Hughes Medical Institute Investigators; T.J. is a David H. Koch Professor of Biology, and a Daniel K. Ludwig Scholar