Responsible Brains: Neuroscience, Law, and Human Culpability

[This download includes the table of contents and chapter 1.] When we praise, blame, punish, or reward people for their actions, we are holding them responsible for what they have done. Common sense tells us that what makes human beings responsible has to do with their minds and, in particular, the relationship between their minds and their actions. Yet the empirical connection is not necessarily obvious. The “guilty mind” is a core concept of criminal law, but if a defendant on trial for murder were found to have serious brain damage, which brain parts or processes would have to be damaged for him to be considered not responsible, or less responsible, for the crime? The authors argue that evidence from neuroscience and the other cognitive sciences can illuminate the nature of responsibility and agency. They go on to offer a novel and comprehensive neuroscientific theory of human responsibility

Torque control system

System stabilizes aximuth of gondolas which are carried by high-altitude balloons as platforms for tracking telescopes. When telescopes must be constantly aimed at specific targets, control system stabilizes gondola to within 5 arc-seconds

IL-15 sustains IL-7R-independent ILC2 and ILC3 development

The signals that maintain tissue-resident innate lymphoid cells (ILC) in different microenvironments are incompletely understood. Here we show that IL-7 receptor (IL-7R) is not strictly required for the development of any ILC subset, as residual cells persist in the small intestinal lamina propria (siLP) of adult and neonatal Il7ra(−/−) mice. Il7ra(−/−) ILC2 primarily express an ST2(−) phenotype, but are not inflammatory ILC2. CCR6(+) ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra(−/−) siLP. All ILC subsets are functionally competent in vitro, and are sufficient to provide enhanced protection to infection with C. rodentium. IL-15 equally sustains wild-type and Il7ra(−/−) ILC survival in vitro and compensates for IL-7R deficiency, as residual ILCs are depleted in mice lacking both molecules. Collectively, these data demonstrate that siLP ILCs are not completely IL-7R dependent, but can persist partially through IL-15 signalling

Enantioselective Total Synthesis of Macfarlandin C, a Spongian Diterpenoid Harboring a Concave-Substituted cis-Dioxabicyclo[3.3.0]octanone Fragment.

The enantioselective total synthesis of the rearranged spongian diterpenoid (-)-macfarlandin C is reported. This is the first synthesis of a rearranged spongian diterpenoid in which the bulky hydrocarbon fragment is joined via a quaternary carbon to the highly hindered concave face of the cis-2,8-dioxabicyclo[3.3.0]octan-3-one moiety. The strategy involves a late-stage fragment coupling between a tertiary carbon radical and an electrophilic butenolide resulting in the stereoselective formation of vicinal quaternary and tertiary stereocenters. A stereoselective Mukaiyama hydration that orients a pendant carboxymethyl side chain cis to the bulky octahydronapthalene substituent was pivotal in fashioning the challenging concave-substituted cis-dioxabicyclo[3.3.0]octanone fragment

Language-related domain-specific and domain-general systems in the human brain.

While a long history of neuropsychological research places language function within a primarily left-lateralized frontotemporal system, recent neuroimaging work has extended this language network to include a number of regions traditionally thought of as 'domain-general'. These include dorsal frontal, parietal, and medial temporal lobe regions known to underpin cognitive functions such as attention and memory. In this paper, we argue that these domain-general systems are not required for language processing and are instead an artefact of the tasks typically used to study language. Recent work from our lab shows that when syntactic processing - arguably the only domain-specific language function - is measured in a task-free, naturalistic manner, only the left-lateralized frontotemporal syntax system and auditory network are activated. When syntax is measured within the context of a task, several other domain-general networks come online and are functionally connected to the frontotemporal system. While we have long argued that syntactic processing does not occur in isolation but is processed in parallel with semantics and pragmatics - functions of the wider language system - our recent work makes a strong case for the domain-specificity of the frontotemporal syntax system and its autonomy from domain-general networks

Chromatin proteins and RNA are associated with DNA during all phases of mitosis.

Mitosis brings about major changes to chromosome and nuclear structure. We used recently developed proximity ligation assay-based techniques to investigate the association with DNA of chromatin-associated proteins and RNAs in Drosophila embryos during mitosis. All groups of tested proteins, histone-modifying and chromatin-remodeling proteins and methylated histones remained in close proximity to DNA during all phases of mitosis. We also found that RNA transcripts are associated with DNA during all stages of mitosis. Reduction of H3K27me3 levels or elimination of RNAs had no effect on the association of the components of PcG and TrxG complexes to DNA. Using a combination of proximity ligation assay-based techniques and super-resolution microscopy, we found that the number of protein-DNA and RNA-DNA foci undergoes significant reduction during mitosis, suggesting that mitosis may be accompanied by structural re-arrangement or compaction of specific chromatin domains

Royal College of Obstetricians and Gynaecologists guidelines: How evidence-based are they?

Evidence-based medicine aims to translate scientific research into good medical practice. The Royal College of Obstetricians and Gynaecologists publishes recommendations and guidelines to guide clinicians in decision-making. In this study, the evidence base underlying the ‘Green-top Guidelines’ has been analysed in order to establish the quality of research underlying recommendations. During this descriptive study of 1,682 individual recommendations, the authors found that only 9–12% of the guidelines were based on the best quality (Grade A) evidence. The authors believe that this type of analysis serves to provide greater clarity for clinicians and patients using guidelines and recommendations in the field of obstetrics and gynaecology to make collaborative clinical decisions

Strain‐Release Driven Spirocyclization of Azabicyclo[1.1.0]butyl Ketones

Due to their intrinsic rigidity, three‐dimensionality and structural novelty, spirocyclic molecules have become increasingly sought‐after moieties in drug discovery. Herein, we report a strain‐release driven synthesis of azetidine‐containing spirocycles by harnessing the inherent ring strain of the azabicyclo[1.1.0]butane (ABB) fragment. Novel ABB‐ketone precursors bearing silyl‐protected alcohols were synthesized in a single step and shown to engage in electrophile‐induced spirocyclization‐desilylation reactions. Primary, secondary and tertiary silyl ethers were effectively transformed into a library of new spiro‐azetidines, with a range of substituents and ring sizes. In addition, the products are generated with synthetically useful ketone and protected‐amine functional groups, which provides the potential for further elaboration and for this chemistry to be utilized in the rapid assembly of medicinally relevant compounds

What makes for a 'good' or 'bad' paediatric diabetes service from the viewpoint of children, young people, carers and clinicians? A synthesis of qualitative findings

Background: There is mounting evidence that experience of care is a crucial part of the pathway for successful management of long-term conditions. Design and objectives: To carry out (1) a systematic mapping of qualitative evidence to inform selection of studies for the second stage of the review; and (2) a narrative synthesis addressing the question, What makes for a ‘good’ or a ‘bad’ paediatric diabetes service from the viewpoint of children, young people, carers and clinicians? Results: The initial mapping identified 38 papers. From these, the findings of 20 diabetes-focused papers on the views on care of ≥650 children, parents and clinicians were synthesised. Only five studies included children under 11 years. Children and young people across all age groups valued positive, non-judgemental and relationship-based care that engaged with their social, as well as physical, health. Parents valued provision responsive to the circumstances of family life and coordinated across services. Clinicians wanting to engage with families beyond a child's immediate physical health described finding this hard to achieve in practice. Limitations: Socioeconomic status and ethnicity were poorly reported in the included studies. Conclusions: In dealing with diabetes, and engaging with social health in a way valued by children, parents and clinicians, not only structural change, such as more time for consultation, but new skills for reworking relations in the consultation may be required