Analysis for Science Librarians of the 2018 Nobel Prize in Physiology or Medicine: The Life and Work of James P. Allison and Tasuku Honjo

On October 1, 2018, James P. Allison and Tasuku Honjo were awarded the 2018 Physiology or Medicine Nobel for their work leading to Immune Checkpoint Inhibition (ICI). ICI is the fourth pillar of cancer treatment and has been used to treat previously un-treatable cancers. Allison discovered that the protein CTLA-4 acts as a T cell brake while Honjo discovered another T cell brake, PD-1. Releasing these brakes allows the immune system to attack tumors, sometimes leading to complete elimination. While there is still more research to be done, Allison’s and Honjo’s work is a breakthrough in cancer immunotherapy

Non-invasive analysis of intestinal development in preterm and term infants using RNA-Sequencing

The state and development of the intestinal epithelium is vital for infant health, and increased understanding in this area has been limited by an inability to directly assess epithelial cell biology in the healthy newborn intestine. To that end, we have developed a novel, noninvasive, molecular approach that utilizes next generation RNA sequencing on stool samples containing intact epithelial cells for the purpose of quantifying intestinal gene expression. We then applied this technique to compare host gene expression in healthy term and extremely preterm infants. Bioinformatic analyses demonstrate repeatable detection of human mRNA expression, and network analysis shows immune cell function and inflammation pathways to be up-regulated in preterm infants. This study provides incontrovertible evidence that whole-genome sequencing of stool-derived RNA can be used to examine the neonatal host epithelial transcriptome in infants, which opens up opportunities for sequential monitoring of gut gene expression in response to dietary or therapeutic interventions

Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns

Hydrogen Macro System Model User Guide, Version 1.2.1

The Hydrogen Macro System Model (MSM) is a simulation tool that links existing and emerging hydrogen-related models to perform rapid, cross-cutting analysis. It allows analysis of the economics, primary energy-source requirements, and emissions of hydrogen production and delivery pathways

Family doctor-driven follow-up for adult childhood cancer survivors supported by a web-based survivor care plan

To facilitate family doctor-driven follow-up for adult childhood cancer survivors, we developed a survivor care plan (SCP) for adult survivors and their family doctors. The SCP was accessible for survivors and their family doctors on a secure website and as a printed booklet. It included data on diagnosis, treatment and potential risks as well as recommendations for follow-up. Childhood cancer survivors who were off-treatment >= 5 years, aged >= 18 years and not involved in a long-term follow-up program were eligible. They were advised to visit their family doctor. The endpoints were numbers of participants, adherence of family doctors to the guidelines and satisfaction ratings. The eligibility criteria were fulfilled by 108 survivors. Three family doctors and 15 survivors refused, 10 survivors were non-responders. Of the remaining 80 survivors, 73 survivors visited 72 family doctors. Sixty-nine (96%) family doctors returned data of whom 60 (83%) fully adhered to the recommended tests. The majority of survivors and family doctors were satisfied about the SCP. A (web-based) SCP for survivors and family doctors can serve as an effective communication vehicle to provide adequate shared care by the long-term follow-up clinic and family doctors

Dislocation interactions during low-temperature plasticity of olivine and their impact on the evolution of lithospheric strength

The strength of the lithosphere is typically modelled based on constitutive equations for steady-state flow. However, strain hardening may cause significant evolution of strength in the colder load-bearing portion of the lithosphere. Recent rheological data from low-temperature deformation experiments on olivine suggest that strain hardening occurs due to the presence of temperature-independent back stresses generated by long-range elastic interactions among dislocations. These interpretations provided the basis for a flow law that incorporates hardening by the development of back stress. Here, we test this dislocation-interaction hypothesis by examining the microstructures of olivine samples deformed plastically at room temperature either in a deformation-DIA apparatus at differential stresses of ≤4.3GPa or in a nanoindenter at applied contact stresses of ≥10.2GPa. High-angular resolution electron backscatter diffraction maps reveal the presence of geometrically necessary dislocations with densities commonly above 1014m−2 and intragranular heterogeneities in residual stress on the order of 1 GPa in both sets of samples. Scanning transmission electron micrographs reveal straight dislocations aligned in slip bands and interacting with dislocations of other types that act as obstacles. The resulting accumulations of dislocations in their slip planes, and associated stress heterogeneities, are consistent with strain hardening resulting from long-range back-stresses acting among dislocations and thereby support the form of the flow law for low-temperature plasticity. Based on these observations, we predict that back stresses among dislocations will impart significant mechanical anisotropy to deformed lithosphere by enhancing or reducing the effective stress. Therefore, strain history, with associated microstructural and micromechanical evolution, is an important consideration for models of lithospheric strength. The microstructural observations also provide new criteria for identifying the operation of back-stress induced strain hardening in natural samples and therefore provide a means to test the applicability of the flow law for low-temperature plasticity.This research was supported by Natural Environment Research Council grants NE/M000966/1 to LNH, AJW, and DW and 1710DG008/JC4 to LNH and AJW; European Plate Observing System Transnational Access grant EPOS-TNA-MSL 2018-022 to LNH; Advanced Photon Source General User Proposal 55176 to LNH, DLG, and WBD; and National Science Foundation Awards EAR-1361319 to WBD, EAR-1625032 to JMW, and EAR-1806791 to KMK

Osteoid osteoma of the femur in a 7-month-old infant treated with radiofrequency ablation

Osteoid osteoma occurs most commonly in children, adolescents, and young adults between the ages of 5 and 30 years. In the preschool age group, it is quite uncommon, accounting for only 3–8% of all osteoid osteoma cases. We report a case of osteoid osteoma in a 7-month-old infant, who presented with decreased use of the right lower extremity due to pain. Magnetic resonance imaging (MRI) showed an atypical appearance. A biopsy of the lesion, with histopathological examination, confirmed the diagnosis of osteoid osteoma. Radiofrequency ablation (RFA) of the nidus under computed tomography (CT) guidance was performed. The patient developed a recurrence after 3 months, which was treated with a second RFA. On subsequent follow-up, the infant did not show signs of pain after 1 month. In summary, this case report shows that osteoid osteoma can present in early infancy and can be successfully treated with RFA at this age, however, recurrence after the procedure can occur and close follow-up is recommended

Stage 4 neuroblastoma: sequential hemi-body irradiation or high-dose chemotherapy plus autologous haemopoietic stem cell transplantation to consolidate primary treatment

The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988–June 1994) and sequential high-dose cyclophosphamide, etoposide, mitoxantrone+L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994–1999). Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P=0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted