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The article examines automation of data science processes including data engineering, model building, and data exploration. The automation of machine learning processes used by data scientists is described along with elements of data engineering including data organization, data quality, and data transformation and the automation of computer model maintenance and monitoring is called for.

Cell therapy is one of the fastest growing areas in the pharmaceutical industry, with considerable therapeutic potential. However, substantial challenges regarding the utility of these therapies will need to be addressed before they can become mainstream medicines with applicability similar to that of small molecules or monoclonal antibodies. Engineered T cells have achieved success in the treatment of blood cancers, with four chimeric antigen receptor (CAR)-T cell therapies now approved for the treatment of B cell malignancies based on their unprecedented efficacy in clinical trials. However, similar results have not yet been achieved in the treatment of the much larger patient population with solid tumours. For cell therapies to become mainstream medicines, they may need to offer transformational clinical effects for patients and be applicable in disease settings that remain unaddressed by simpler approaches. This Perspective provides an industry perspective on the progress achieved by engineered T cell therapies to date and the opportunities and current barriers for accessing broader patient populations, and discusses the solutions and new development strategies required to fully industrialize the therapeutic potential of engineered T cells as medicines.

Toxicological information as needed for risk assessments of chemical compounds is often sparse. Unfortunately, gathering new toxicological information experimentally often involves animal testing. Simulated alternatives, e.g., quantitative structure–activity relationship (QSAR) models, are preferred to infer the toxicity of new compounds. Aquatic toxicity data collections consist of many related tasks─each predicting the toxicity of new compounds on a given species. Since many of these tasks are inherently low-resource, i.e., involve few associated compounds, this is challenging. Meta-learning is a subfield of artificial intelligence that can lead to more accurate models by enabling the utilization of information across tasks. In our work, we benchmark various state-of-the-art meta-learning techniques for building QSAR models, focusing on knowledge sharing between species. Specifically, we employ and compare transformational machine learning, model-agnostic meta-learning, fine-tuning, and multi-task models. Our experiments show that established knowledge-sharing techniques outperform single-task approaches. We recommend the use of multi-task random forest models for aquatic toxicity modeling, which matched or exceeded the performance of other approaches and robustly produced good results in the low-resource settings we studied. This model functions on a species level, predicting toxicity for multiple species across various phyla, with flexible exposure duration and on a large chemical applicability domain.

An interview with Keyla Haynes, a stylist from Naturally Chic Salon, Sarah White, a curl specialist from Cornwall Curl Specialist and Christine McMillan from Rock Paper Scissors Buford is presented. They share their favorite quotes, celebrity curl crushes, impactful books, and inspirational messages for curly women, emphasizing the importance of confidence, embracing individuality, and finding beauty in one's natural curls.

Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan-Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. J Natl Cancer Inst 2010;102:1388-1397 DOI: 10.1093/jnci/djq310

FULL DENTURE IMPRESSIONS The denture impressions technique used by most dentists involves doing a first impression with a stock tray using an alginate impression material. After the high-durometer VPS sets, the patient opens while your fingers retain the impression on the opposing arch. Patient comfort PARTIAL DENTURE IMPRESSIONS In my experience working with complex partial dentures, it's very difficult to create an accurate major connector and minor connectors and to capture the soft tissue using digital impressions. A single impression was taken for the crown, similar to how a copper band impression is taken, and then a master impression was taken using a high-durometer VPS impression and a light-body impression material to pick up all of the details. [Extracted from the article]

OBJECTIVE--FFAR1/GPR40 is a G-protein-coupled receptor expressed predominantly in pancreatic islets mediating free fatty acid--induced insulin secretion. However, the physiological role of FFAR1 remains controversial. It was previously reported that FFAR1 knockout ([Ffar1.sup.-/-]) mice were resistant to high-fat diet--induced hyperinuslinemia, hyperglycemia, hypertriglyceridemia, and hepatic steatosis. A more recent report suggested that although FFAR1 was necessary for fatty acid--induced insulin secretion in vivo, deletion of FFAR1 did not protect pancreatic islets against fatty acid--induced islet dysfunction. This study is designed to investigate FFAR1 function in vivo using a third line of independently generated [Ffar1.sup.-/-] mice in the C57BL/6 background. RESEARCH DESIGN AND METHODS--We used CL-316,243, a β3 adrenergic receptor agonist, to acutely elevate blood free fatty acids and to study its effect on insulin secretion in vivo. [Ffar1.sup.+/+] (wild-type) and [Ffar1.sup.-/-] (knockout) mice were placed on two distinct high-fat diets to study their response to diet-induced obesity. RESULTS--Insulin secretion was reduced by ~50% in [Ffar1.sup.-/-] mice, confirming that FFAR1 contributes significantly to [Ffar1.sup.+/+] acid stimulation of insulin secretion in vivo. However, [Ffar1.sup.+/+] and [Ffar1.sup.-/-] mice had similar weight, adiposity, and hyperinsulinemia on high-fat diets, and [Ffar1.sup.-/-] mice showed no improvement in glucose or insulin tolerance tests. In addition, high-fat diet induced comparable levels of lipid accumulation in livers of [Ffar1.sup.+/+] and [Ffar1.sup.-/-] mice. CONCLUSIONS--FFAR1 is required for normal insulin secretion in response to fatty acids; however, [Ffar1.sup.-/-] mice are not protected from high-fat diet-induced insulin resistance or hepatic steatosis., Fatty acids are involved in a diverse array of physiological functions in a variety of tissues. Many of the effects of fatty acids are thought to be mediated by intracellular [...]

The dentist can provide the highest quality restorations that are the most beautiful in the world, but if the patient experience is not great, you will fail. I did find a tech answer: an automated system (apedental.com) that contacts patients via texts-not only post-op but also when welcoming new patients, reminding people that they didn't schedule their next followup or recall, and more. Consultants have been working with dental practices for years, teaching and training staffs to provide the highest quality patient experience. [Extracted from the article]

The article discusses the effect of mandatory sustainability reporting on small and medium-sized enterprises (SMEs) worldwide, even if they are not directly affected by new regulations. Although only large companies are mandated to report environmental, social, and governance (ESG) data, SMEs in their value chain will be pressured to do so by large buyers of their products and services. This will be the case with new EU regulations and instruments covering value chains.

BRITS AROUND THE WORLD Terry Ellis brought along his well-appointed luggage to last summer's annual general meeting of the British Phonographic Industry in London. Not literally, of course, but figuratively. […]

The potential of artificial intelligence (AI) applied to clinical data from electronic health records (EHRs) to improve early detection for pancreatic and other cancers remains underexplored. The Kenner Family Research Fund, in collaboration with the Cancer Biomarker Research Group at the National Cancer Institute, organized the workshop entitled: “Early Detection of Pancreatic Cancer: Opportunities and Challenges in Utilizing Electronic Health Records (EHR)” in March 2021. The workshop included a select group of panelists with expertise in pancreatic cancer, EHR data mining, and AI-based modeling. This review article reflects the findings from the workshop and assesses the feasibility of AI-based data extraction and modeling applied to EHRs. It highlights the increasing role of data sharing networks and common data models in improving the secondary use of EHR data. Current efforts using EHR data for AI-based modeling to enhance early detection of pancreatic cancer show promise. Specific challenges (biology, limited data, standards, compatibility, legal, quality, AI chasm, incentives) are identified, with mitigation strategies summarized and next steps identified.

The article discusses the authors' research into the behavior of algorithms for solving NP-complete problems, focusing on the argument that statistical methods can predict algorithm runtimes to a high level of confidence. Topics include analysis of research into empirical hardness models (EHMs), theoretical insights to be gained by use of models to understand algorithms, and practical applications of EHMs for computer scientists. Example problems and graphs of runtime findings and other data results are provided.

Kinases are frequently studied in the context of anticancer drugs. Their involvement in cell responses, such as proliferation, differentiation, and apoptosis, makes them interesting subjects in multitarget drug design. In this study, a workflow is presented that models the bioactivity spectra for two panels of kinases: (1) inhibition of RET, BRAF, SRC, and S6K, while avoiding inhibition of MKNK1, TTK, ERK8, PDK1, and PAK3, and (2) inhibition of AURKA, PAK1, FGFR1, and LKB1, while avoiding inhibition of PAK3, TAK1, and PIK3CA. Both statistical and structure-based models were included, which were thoroughly benchmarked and optimized. A virtual screening was performed to test the workflow for one of the main targets, RET kinase. This resulted in 5 novel and chemically dissimilar RET inhibitors with remaining RET activity of <60% (at a concentration of 10 μM) and similarities with known RET inhibitors from 0.18 to 0.29 (Tanimoto, ECFP6). The four more potent inhibitors were assessed in a concentration range and proved to be modestly active with a pIC50value of 5.1 for the most active compound. The experimental validation of inhibitors for RET strongly indicates that the multitarget workflow is able to detect novel inhibitors for kinases, and hence, this workflow can potentially be applied in polypharmacology modeling. We conclude that this approach can identify new chemical matter for existing targets. Moreover, this workflow can easily be applied to other targets as well.

ABSTRACTThe present study examines the influence of a 10 km race of runners with different performance levels on time-domain measures and non-linear dynamics of HRV. Twenty-two male recreational to elite runners performed a self-paced 10 km race on asphalt with flat profile. The participants were divided into two performance groups based on their 10 km total time with a split at 40 min (fTT: fast total times, sTT: slow total times). During the race (Begin, Mid-Point, End), heart rate and RR-intervals were recorded continuously. Besides HRV time-domain measurements, fractal correlation properties using short-term scaling exponent alpha1 of Detrended Fluctuation Analysis (DFA) were calculated. Mean total time from fTT was significant faster compared to sTT (35:14 ± 03:15 min:sec vs. 46:34 ± 05:46 min:sec). While RMSSD and SDNN diminished strongly during the race with no differences between groups, we observed significant lower values in DFA-alpha1 at Begin for fTT. In comparison of Begin vs. Mid-Point as well as Begin vs. End a significant decrease could be determined in DFA-alpha1 for sTT. The earlier loss of correlation properties during Begin in fTT implies a fastened alteration of cardiac autonomic regulation in order to match an all-out performance attractor for maximal endurance performance.

For food emulsions containing enzymatically modified egg yolk, the conventional Folch extraction does not fully recover the polar lysophospholipids. This can be overcome by repeated methanol extractions. After solvent evaporation, the extracted (lyso)phospholipids are solubilized into mixed micelles with cholate as a detergent. The solubilized (lyso)phospholipids can be accurately quantified by 31P NMR with recoveries ranging between 96% and 108%. Detection at a high (16.4 T) relative to a mainstream (9.4 T) magnetic field strength did not offer a significant advantage since the slow molecular tumbling of the mixed micelles increased line widths. This was due to field-strength-dependent chemical shift anisotropy relaxation. Method precision is similar at 9.4 and 16.4 T, with within-laboratory reproducibilities of 7–22% and 12–25%, respectively. The method can be implemented as a routine analytical procedure at 9.4 T (400 MHz NMR spectrometer), and the limits of detection and quantification are adequate for the verification of the standard of identity of a mayonnaise prepared with enzymatically modified egg yolk.

Avoid premature commitment, seek design alternatives, and automatically generate performance-optimized software. [ABSTRACT FROM AUTHOR]

Doubly labeled water is gold standard for measuring total energy expenditure (TEE). Measurements using the method are sensitive to the isotope dilution space ratio (DSR). Accuracy and precision of the method might be improved if we could identify factors influencing DSR.

Alzheimer’s disease (AD) is a complex neurodegenerative process that involves altered brain immune, neuronal and metabolic functions. Understanding the underlying mechanisms has relied on mouse models that mimic components of AD pathology. We used gel-free, label-free LC–MS/MS to quantify protein and phosphopeptide levels in brains of APPSwDI/NOS2–/– (CVN–AD) mice. CVN–AD mice show a full spectrum of AD-like pathology, including amyloid deposition, hyperphosphorylated and aggregated tau, and neuronal loss that worsens with age. Tryptic digests, with or without phosphopeptide enrichment on an automated titanium dioxide LC system, were separated by online two-dimensional LC and analyzed on a Waters Synapt G2 HDMS, yielding relative expression for >950 proteins and >1100 phosphopeptides. Among differentially expressed proteins were known markers found in humans with AD, including GFAP and C1Q. Phosphorylation of connexin 43, not previously described in AD, was increased at 42 weeks, consistent with dysregulation of gap junctions and activation of astrocytes. Additional alterations in phosphoproteins suggests dysregulation of mitochondria, synaptic transmission, vesicle trafficking, and innate immune pathways. These data validate the CVN–AD mouse model of AD, identify novel disease and age-related changes in the brain during disease progression, and demonstrate the utility of integrating unbiased and phosphoproteomics for understanding disease processes in AD.

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IntroductionMeaningful patient engagement (PE) can enhance medicines’ development. However, the current PE landscape is fragmentary and lacking comprehensive guidance.MethodsWe systematically searched for PE initiatives (SYNaPsE database/publications). Multistakeholder groups integrated these with their own PE expertise to co-create draft PE Quality Guidance which was evaluated by public consultation. Projects exemplifying good PE practice were identified and assessed against PE Quality Criteria to create a Book of Good Practices (BOGP).ResultsSeventy-six participants from 51 organisations participated in nine multistakeholder meetings (2016–2018). A shortlist of 20relevant PE initiatives (from 170 screened) were identified. The co-created INVOLVE guidelines provided the main framework for PE Quality Guidance and was enriched with the analysis of the PE initiatives and the PE expertise of stakeholders. Seven key PE Quality Criteria were identified. Public consultation yielded 67 responses from diverse backgrounds. The PE Quality Guidance was agreed to be useful for achieving quality PE in practice, understandable, easy to use, and comprehensive. Overall, eight initiatives from the shortlist and from meeting participants were selected for inclusion in the BOGP based on demonstration of PE Quality Criteria and willingness of initiative owners to collaborate.DiscussionThe PE Quality Guidance and BOGP are practical resources which will be continually updated in response to user feedback. They are not prescriptive, but rather based on core principles, which can be applied according to the unique needs of each interaction and initiative. Implementation of the guidance will facilitate improved and systematic PE across the medicines’ development lifecycle.

The article reports on electronic data processing (EDP) and the outlook for office automation in the United States. An EDP study in the San Francisco Bay Area found that the introduction of computers in organizations affects all job categories quantitatively and qualitatively. Statistics show that only one job is created for the five jobs eliminated by office automation. Topics include the salaries of programmers, the trend toward recentralization, short-term displacement effects from EDP, growth in the position of key-punch operators, stagnation at the middle management level, and changes in organizational structure and communication channels.

The AAAI-2000 Workshop Program was held Sunday and Monday, 30-31 July 2000 at the Hyatt Regency Austin and the Austin Convention Center in Austin, Texas. The 15 workshops held were […], The AAAI-2000 Workshop Program was held Sunday and Monday, 30-31 July 2000 at the Hyatt Regency Austin and the Austin Convention Center in Austin, Texas. The 15 workshops held were (1) "Agent-Oriented Information Systems," (2) "Artificial Intelligence and Music," (3) "Artificial Intelligence and Web Search," (4) "Constraints and AI Planning," (5) "Integration of AI and OR: Techniques for Combinatorial Optimization," (6) "Intelligent Lessons Learned Systems," (7) "Knowledge-Based Electronic Markets," (8) "Learning from Imbalanced Data Sets," (9) "Learning Statistical Models from Relational Data," (10) "Leveraglng Probability and Uncertainty in Computation, (11) "Mobile Robotic Competition and Exhibition,' (12) "New Research Problems for Machine Learning," (13) "Parallel and Distributed Search for Reasoning," (14) "Representational Issues for Real-World Planning Systems," and (15) "Spatial and Temporal Granularity."

Background: Exercise intensities are prescribed using specific intensity zones (moderate, heavy, and severe) determined by a ‘lower’ and a ‘higher’ threshold. Typically, ventilatory (VT) or blood lactate thresholds (LT), and critical power/speed concepts (CP/CS) are used. Various heart rate variability-derived thresholds (HRVTs) using different HRV indices may constitute applicable alternatives, but a systematic review of the proximity of HRVTs to established threshold concepts is lacking. Objective: This systematic review aims to provide an overview of studies that determined HRVTs during endurance exercise in healthy adults in comparison with a reference VT and/or LT concept. Methods: A systematic literature search for studies determining HRVTs in healthy individuals during endurance exercise and comparing them with VTs or LTs was conducted in Scopus, PubMed and Web of Science (until January 2022). Studies claiming to describe similar physiological boundaries to delineate moderate from heavy (HRVTlow vs. VTlow and/or LTlow), and heavy from severe intensity zone (HRVThigh vs. VThigh and/or LThigh) were grouped and their results synthesized. Results: Twenty-seven included studies (461 participants) showed a mean difference in relative HR between HRVTlow and VTlow of − 0.6%bpm in weighted means and 0.02%bpm between HRVTlow and LTlow. Bias between HR at HRVTlow and VTlow was 1 bpm (limits of agreement (LoA): − 10.9 to 12.8 bpm) and 2.7 bpm (LoA: − 20.4 to 25.8 bpm) between HRVTlow and LTlow. Mean difference in HR between HRVThigh and VThigh was 0.3%bpm in weighted means and 2.9%bpm between HRVThigh and LThigh while bias between HR at HRVThigh and VThigh was − 4 bpm (LoA: − 17.9 to 9.9 bpm) and 2.5 bpm (LoA: − 12.1 to 17.1 bpm) between HRVThigh and LThigh. Conclusion: HRVTlow seems to be a promising approach for the determination of a ‘lower’ threshold comparable to VTlow and potentially for HRVThigh compared to VThigh, although the latter needs further empirical evaluation. LoA for both intensity zone boundaries indicates bias of HRVTs on an individual level. Taken together, HRVTs can be a promising alternative for prescribing exercise intensity in healthy, male athletes undertaking endurance activities but due to the heterogeneity of study design, threshold concepts, standardization, and lack of female participants, further research is necessary to draw more robust and nuanced conclusions.

Accumulation of fibrillar amyloid β protein in blood vessels of the brain, a condition known as cerebral amyloid angiopathy (CAA), is a common pathology of elderly individuals, a prominent comorbidity of Alzheimer disease, and a driver of vascular cognitive impairment and dementia. Although several transgenic mouse strains have been generated that develop varying levels of CAA, consistent models of associated cerebral microhemorrhage and vasculopathy observed clinically have been lacking. Reliable preclinical animal models of CAA and microhemorrhage are needed to investigate the molecular pathogenesis of this condition. Herein, we describe the generation and characterization of a novel transgenic rat (rTg-DI) that produces low levels of human familial CAA Dutch/Iowa E22Q/D23N mutant amyloid β protein in brain and faithfully recapitulates many of the pathologic aspects of human small-vessel CAA. rTg-DI rats exhibit early-onset and progressive accumulation of cerebral microvascular fibrillar amyloid accompanied by early-onset and sustained behavioral deficits. Comparable to CAA in humans, the cerebral microvascular amyloid in rTg-DI rats causes capillary structural alterations, promotes prominent perivascular neuroinflammation, and produces consistent, robust microhemorrhages and small-vessel occlusions that are readily detected by magnetic resonance imaging. The rTg-DI rats provide a new model to investigate the pathogenesis of small-vessel CAA and microhemorrhages, to develop effective biomarkers for this condition and to test therapeutic interventions.

Stimulator of interferon genes (STING) is a receptor in the endoplasmic reticulum that propagates innate immune sensing of cytosolic pathogen-derived and self DNA1. The development of compounds that modulate STING has recently been the focus of intense research for the treatment of cancer and infectious diseases and as vaccine adjuvants2. To our knowledge, current efforts are focused on the development of modified cyclic dinucleotides that mimic the endogenous STING ligand cGAMP; these have progressed into clinical trials in patients with solid accessible tumours amenable to intratumoral delivery3. Here we report the discovery of a small molecule STING agonist that is not a cyclic dinucleotide and is systemically efficacious for treating tumours in mice. We developed a linking strategy to synergize the effect of two symmetry-related amidobenzimidazole (ABZI)-based compounds to create linked ABZIs (diABZIs) with enhanced binding to STING and cellular function. Intravenous administration of a diABZI STING agonist to immunocompetent mice with established syngeneic colon tumours elicited strong anti-tumour activity, with complete and lasting regression of tumours. Our findings represent a milestone in the rapidly growing field of immune-modifying cancer therapies.

Immune cell functions are regulated by co-inhibitory and co-stimulatory receptors. The first two generations of cancer immunotherapy agents consist primarily of antagonist antibodies that block negative immune checkpoints, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte protein 4 (CTLA4). Looking ahead, there is substantial promise in targeting co-stimulatory receptors with agonist antibodies, and a growing number of these agents are making their way through various stages of development. This Review discusses the key considerations and potential pitfalls of immune agonist antibody design and development, their differentiating features from antagonist antibodies and the landscape of agonist antibodies in clinical development for cancer treatment.

Reported are the syntheses, crystal structures, and electronic structures of six rare-earth metal–lithium stannides with the general formulas RE3Li4–xSn4+x(RE = La–Nd, Sm) and Eu7Li8–xSn10+x. These new ternary compounds have been synthesized by high-temperature reactions of the corresponding elements. Their crystal structures have been established using single-crystal X-ray diffraction methods. The RE3Li4–xSn4+xphases crystallize in the orthorhombic body-centered space group Immm(No. 71) with the Zr3Cu4Si4structure type (Pearson code oI22), and the Eu7Li8–xSn10+xphase crystallizes in the orthorhombic base-centered space group Cmmm(No. 65) with the Ce7Li8Ge10structure type (Pearson code oC50). Both structures can be consdered as part of the [RESn2]n[RELi2Sn]mhomologous series, wherein the structures are intergrowths of imaginary RESn2(AlB2-like structure type) and RELi2Sn (MgAl2Cu-like structure type) fragments. Close examination the structures indicates complex occupational Li–Sn disorder, apparently governed by the drive of the structure to achieve an optimal number of valence electrons. This conclusion based on experimental results is supported by detailed electronic structure calculations, carried out using the tight-binding linear muffin-tin orbital method.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decrease in the degree of GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Patient Focused Medicines Development (PFMD) is a not-for-profit independent multinational coalition of patients, patient stakeholders, and the pharmaceutical industry with interests across diverse disease areas and conditions. PFMD aims to facilitate an integrated approach to medicines development with all stakeholders involved early in the development process. A key strength of the coalition that differentiates it from other groups that involve patients or patient groups is that PFMD has patient organizations as founding members, ensuring that the patient perspective is the starting point when identifying priorities and developing solutions to meet patients’ needs. In addition, PFMD has from inception been formed as an equal collaboration among patient groups, patients, and pharmaceutical industry and has adopted a unique trans-Atlantic setup and scope that reflects its global intent. This parity extends to its governance model, which ensures at least equal or greater share of voice for patient group members. PFMD is actively inviting additional members and aims to expand the collaboration to include stakeholders from other sectors. The establishment of PFMD is particularly timely as patient engagement (PE) has become a priority for many health stakeholders and has led to a surge of mostly disconnected activities to deliver this. Given the current plethora of PE initiatives, an essential first step has been to determine, based on a comprehensive mapping, those strategic areas of most need requiring a focused initial effort from the perspective of all stakeholders. PFMD has identified four priority areas that will need to be addressed to facilitate implementation of PE. These are (1) culture and process change, (2) development of a global meta-framework for PE, (3) information exchange, and (4) training. This article discusses these priority themes and ongoing or planned PFMD activities within each.

Several letters to the editor are presented in response to articles in previous issues including an opposition to possible Republican presidential candidates, an appreciation of an article in the June 4, 1951 issue on the 43rd Division of the U.S. Army at Camp Pickett, Virginia, and a call on the revival of the U.S. cavalry in the Korean war.

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Uniformly adopted response criteria are essential for assessment of therapies incorporating conventional chemotherapy and chemoimmunotherapy regimens. Recently, immunomodulatory agents, such as immune checkpoint inhibitors, have demonstrated impressive activity in a broad range of lymphoma histologies. However, these agents may be associated with clinical and imaging findings during treatment suggestive of progressive disease (PD) despite evidence of clinical benefit (eg, tumor flare or pseudo-progression). Considering this finding as PD could lead to patients being prematurely removed from a treatment from which they actually stand to benefit. This phenomenon has been well described with checkpoint blockade therapy in solid tumors and anecdotally seen in lymphoma as well. To address this issue in the context of lymphoma immunomodulatory therapy, a workshop was convened to provide provisional recommendations to modify current response criteria in patients receiving these and future agents in clinical trials. The term “indeterminate response” was introduced to identify such lesions until confirmed as flare/pseudo-progression or true PD by either biopsy or subsequent imaging.