Overcoming provider barriers to therapeutic drug monitoring of tumour necrosis factor inhibitors for rheumatoid arthritis:a qualitative analysis

ObjectiveTherapeutic drug monitoring (TDM) of tumour necrosis factor-α inhibitors (TNFi), by measuring drug levels and/or anti-drug antibodies, is being considered by various international bodies to improve patient health outcomes and the value of care for people with rheumatoid arthritis. Rheumatology care providers may perceive barriers to adopting TNFi TDM within their own clinical practice, limiting the potential for patients and health care systems to benefit. This study aimed to explore the barriers perceived by rheumatologists that may reduce their uptake of TNFi TDM for rheumatoid arthritis.MethodSemi-structured one-to-one telephone interviews were performed with a convenience sample of senior rheumatologists with experience of managing people with rheumatoid arthritis. The interviews explored the rheumatologists’ understanding of TDM and their beliefs about how it can be integrated into their own routine practice. Interviews were audio recorded, transcribed verbatim and anonymized. Transcripts were coded inductively and barriers to using TNFi TDM were identified by thematic framework analysis.ResultA sample of eleven senior rheumatologists were interviewed. The rheumatologists described five barriers to adopting TNFi TDM in routine practice: (i) observing clinical need; (ii) understanding how testing can improve practice; (iii) insufficient clinical evidence; (iv) insufficient resources to pay for testing; and (v) insufficient capability to deliver testing.ConclusionBarriers to adopting TNFi TDM in routine care settings will restrict the ability for patients to benefit from effective monitoring strategies as they begin to emerge. Strategies to overcome these barriers are suggested which will require a coordinated response from stakeholders across health care systems

Lateral hypothalamus is required for context-induced reinstatement of extinguished reward seeking

We studied the role of lateral hypothalamus (LH) in context-induced reinstatement (renewal) of reward seeking. Rats were trained to respond for 4% (v/v) alcoholic beer or 10% (w/v) sucrose reward in one context (Context A) before extinction training in a second context (Context B). On test, rats were returned to the training context, A (ABA), or the extinction context, B (ABB). Return to the training context (ABA) produced robust reinstatement. Reversible inactivation of LH via baclofen/muscimol infusion prevented context-induced reinstatement of beer and sucrose seeking. This prevention was specific to bilateral infusions into LH. We then used the retrograde neuronal tracer cholera toxin b subunit (CTb) combined with detection of the c-Fos protein to identify activated afferents to LH during context-induced reinstatement of beer seeking. Double labeling for c-Fos and CTb revealed a significant recruitment of LH-projecting neurons in nucleus accumbens shell (AcbSh) during reinstatement. These afferents could be classified into two anatomically and functionally distinct groups. First, afferents in the ventral AcbSh projecting to LH were activated during reinstatement. Second, afferents in the dorsomedial AcbSh projecting to LH were activated during test in the extinction context. These recruitments were specific to an AcbSh–LH pathway because they were not observed following CTb injection into the immediately adjacent perifornical hypothalamus. These results show that LH is critical for context-induced reinstatement of reward seeking and that parallel striatal-hypothalamic pathways are recruited following return to the training versus extinction contexts

Eduardo Mujica con Universidad Católica de Chile -Corporación de Televisión

<p>Mean (SEM) percent pre-CS freezing for Experiment 1.</p

Real-time forecasting of pesticide concentrations in soil

peer-reviewedForecasting pesticide residues in soils in real time is essential for agronomic purposes, to manage phytotoxic effects, and in catchments to manage surface and ground water quality. This has not been possible in the past due to both modelling and measurement constraints. Here, the analytical transient probability distribution (pdf) of pesticide concentrations is derived. The pdf results from the random ways in which rain events occur after pesticide application. First-order degradation kinetics and linear equilibrium sorption are assumed. The analytical pdfs allow understanding of the relative contributions that climate (mean storm depth and mean rainfall event frequency) and chemical (sorption and degradation) properties have on the variability of soil concentrations into the future. We demonstrated the two uncertain reaction parameters can be constrained using Bayesian methods. An approach to a Bayesian informed forecast is then presented. With the use of new rapid tests capable of providing quantitative measurements of soil concentrations in the field, real-time forecasting of future pesticide concentrations now looks possible for the first time. Such an approach offers new means to manage crops, soils and water quality, and may be extended to other classes of pesticides for ecological risk assessment purposes

Globally Universal Fractal Pattern of Human Settlements in River Networks

River networks play a key role in the spatial organization of human settlements. Both river networks and human settlements have been found to exhibit regular self-similar patterns, but little is known about the generalized spatial patterns of human settlements embedded within river networks. Here based on night light data, we find a universal fractal structure at the global scale, with both robust Hortonian scaling relationships with the extent of human settlements and statistically significant power law scaling of the power spectra of human area functions. Globally, we find consistent patterns of power law preferential downstream clustering of human settlements across all six populated continents, typically up to 40% of the maximum flow length. This downstream clustering suggests an optimum distribution of humans in large river basins for trade, transport, and natural resource utilization but with attendant implications for human impacts on rivers. Recognition of such spatial patterns helps generalize assessments of human impacts on rivers, with direct implications for management of water quality and biological diversity in river networks

A cognitive pathway to punishment insensitivity

Individuals differ in their sensitivity to the adverse consequences of their actions, leading some to persist in maladaptive behaviors. Two pathways have been identified for this insensitivity: a motivational pathway based on excessive reward valuation and a behavioral pathway based on autonomous stimulus–response mechanisms. Here, we identify a third, cognitive pathway based on differences in punishment knowledge and use of that knowledge to suppress behavior. We show that distinct phenotypes of punishment sensitivity emerge from differences in what people learn about their actions. Exposed to identical punishment contingencies, some people (sensitive phenotype) form correct causal beliefs that they use to guide their behavior, successfully obtaining rewards and avoiding punishment, whereas others form incorrect but internally coherent causal beliefs that lead them to earn punishment they do not like. Incorrect causal beliefs were not inherently problematic because we show that many individuals benefit from information about why they are being punished, revaluing their actions and changing their behavior to avoid further punishment (unaware phenotype). However, one condition where incorrect causal beliefs were problematic was when punishment is infrequent. Under this condition, more individuals show punishment insensitivity and detrimental patterns of behavior that resist experience and information-driven updating, even when punishment is severe (compulsive phenotype). For these individuals, rare punishment acted as a “trap,” inoculating maladaptive behavioral preferences against cognitive and behavioral updating