Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study.

PURPOSE: Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes. PATIENTS AND METHODS: Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS). RESULTS: High PET score was associated with inferior EFS, before (P .4). CONCLUSION: In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL

Species-specific pace of development is associated with differences in protein stability

Although many molecular mechanisms controlling developmental processes are evolutionarily conserved, the speed at which the embryo develops can vary substantially between species. For example, the same genetic program, comprising sequential changes in transcriptional states, governs the differentiation of motor neurons in mouse and human, but the tempo at which it operates differs between species. Using in vitro directed differentiation of embryonic stem cells to motor neurons, we show that the program runs more than twice as fast in mouse as in human. This is not due to differences in signaling, nor the genomic sequence of genes or their regulatory elements. Instead, there is an approximately two-fold increase in protein stability and cell cycle duration in human cells compared with mouse cells. This can account for the slower pace of human development and suggests that differences in protein turnover play a role in interspecies differences in developmental tempo

Why shit happens : amplifying the voices of frontline WASH professionals to reduce failure in the sector

This record includes an extended abstract and MP4 presentation. Presented at the 42nd WEDC International Conference

On Second-Order Monadic Monoidal and Groupoidal Quantifiers

We study logics defined in terms of second-order monadic monoidal and groupoidal quantifiers. These are generalized quantifiers defined by monoid and groupoid word-problems, equivalently, by regular and context-free languages. We give a computational classification of the expressive power of these logics over strings with varying built-in predicates. In particular, we show that ATIME(n) can be logically characterized in terms of second-order monadic monoidal quantifiers

Study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK): study protocol for a patient-blinded, randomised controlled superiority trial of liposomal bupivacaine

Background: Optimising the management of peri-operative pain and recovery following knee replacement has been identified as a patient priority. Current pain relief strategies use opiate-based analgesia; however, up to 50% of patients experience significant side effects. Local anaesthetic incisional infiltration is one alternative. The length of the duration of action is a major limiting factor of current local anaesthetic techniques. Liposomal bupivacaine has been reported to be effective for up to 72 h. This randomised controlled trial will evaluate the clinical and cost effectiveness of liposomal bupivacaine. Methods: SPAARK is a patient-blinded, multi-centre, active comparator, superiority, two-arm, parallel-group randomised controlled trial. Five hundred patients undergoing knee replacement will be recruited and randomised to liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The co-primary outcomes are the Quality of Recovery 40 measured at 72 h post-surgery and also cumulative pain measured daily using a 0–10 visual analogue scale for the first 3 days following surgery. Secondary outcomes include cumulative opioid consumption, fitness for discharge, functional outcomes assessed using the Oxford Knee Score and American Knee Society Score, the EuroQol five dimensions instrument and complications. A cost utility analysis is also planned. Discussion: The clinical effectiveness and cost effectiveness of liposomal bupivacaine have yet to be evaluated in the National Health Service, making this trial appropriate and timely. Trial registration: ISRCTN registry, ISRCTN54191675. Registered on 14 November 2017

Identity and integration of Russian speakers in the Baltic states: a framework for analysis

Following a review of current scholarship on identity and integration patterns of Russian speakers in the Baltic states, this article proposes an analytical framework to help understand current trends. Rogers Brubaker's widely employed triadic nexus is expanded to demonstrate why a form of Russian-speaking identity has been emerging, but has failed to become fully consolidated, and why significant integration has occurred structurally but not identificationally. By enumerating the subfields of political, economic, and cultural ‘stances’ and ‘representations’ the model helps to understand the complicated integration processes of minority groups that possess complex relationships with ‘external homelands’, ‘nationalizing states’ and ‘international organizations’. Ultimately, it is argued that socio-economic factors largely reduce the capacity for a consolidated identity; political factors have a moderate tendency to reduce this capacity, whereas cultural factors generally increase the potential for a consolidated group identity

Research brief : amplifying local voices to reduce failure in the water, sanitation and hygiene sector

There needs to be a culture shift towards greater responsibility, and particularly shared accountability, for water, sanitation, and hygiene (WASH) failures and challenges