Systems thinking and efficiency under emissions constraints: Addressing rebound effects in digital innovation and policy.

Innovations and efficiencies in digital technology have lately been depicted as paramount in the green transition to enable the reduction of greenhouse gas emissions, both in the information and communication technology (ICT) sector and the wider economy. This, however, fails to adequately account for rebound effects that can offset emission savings and, in the worst case, increase emissions. In this perspective, we draw on a transdisciplinary workshop with 19 experts from carbon accounting, digital sustainability research, ethics, sociology, public policy, and sustainable business to expose the challenges of addressing rebound effects in digital innovation processes and associated policy. We utilize a responsible innovation approach to uncover potential ways forward for incorporating rebound effects in these domains, concluding that addressing ICT-related rebound effects ultimately requires a shift from an ICT efficiency-centered perspective to a "systems thinking" model, which aims to understand efficiency as one solution among others that requires constraints on emissions for ICT environmental savings to be realized.

The Feasibility and Impact of Practising Online Forest Bathing to Improve Anxiety, Rumination, Social Connection and Long-COVID Symptoms: A Pilot Study.

BACKGROUND: Long-COVID affects over 144 million people globally. In the absence of treatments, there is a need to establish the efficacy of therapies that improve patient outcomes. Forest bathing has been demonstrated to improve physical and mental outcomes but there is no evidence in Long-COVID patients. Accordingly, this pilot study sought to determine the feasibility and effectiveness of online forest bathing in adults with Long-COVID. METHODS: Feasibility was assessed by monitoring retention rates and participant feedback. In a waitlist controlled, repeated measures design, 22 Long-COVID patients completed weekly online surveys during a four-week waitlist control period, before engaging in four weekly online forest bathing sessions, completing post-intervention surveys following each session. RESULTS: In terms of retention, 27% did not provide post-intervention data, reasons for non-adherence were: feeling too ill, having medical appointments, or having career responsibilities. Compared with the waitlist control period, there were statistically significant improvements in Anxiety (49% decrease), Rumination (48% decrease), Social Connection (78% increase), and Long-COVID symptoms (22% decrease). Written qualitative comments indicated that participants experienced feelings of calm and joy, felt more connected socially and with nature, and experienced a break from the pain and rumination surrounding their illness. CONCLUSIONS: Online Forest bathing resulted in significant improvements in well-being and symptom severity and could be considered an accessible and inexpensive adjunct therapy for Long-COVID patients. Where people have limited access to in-person nature, virtual nature may offer an alternative to improve health and well-being outcomes.

Iron-dependent gene expression in Actinomyces oris.

BACKGROUND: Actinomyces oris is a Gram-positive bacterium that has been associated with healthy and diseased sites in the human oral cavity. Most pathogenic bacteria require iron to survive, and in order to acquire iron in the relatively iron-scarce oral cavity A. oris has been shown to produce iron-binding molecules known as siderophores. The genes encoding these siderophores and transporters are thought to be regulated by the amount of iron in the growth medium and by the metal-dependent repressor, AmdR, which we showed previously binds to the promoter of proposed iron-regulated genes. OBJECTIVE: The purpose of this study was to characterize siderophore and associated iron transport systems in A. oris. DESIGN: We examined gene expression of the putative iron transport genes fetA and sidD in response to low- and high-iron environments. One of these genes, sidD, encoding a putative Fe ABC transporter protein, was insertionally inactivated and was examined for causing growth defects. To gain a further understanding of the role of iron metabolism in oral diseases, clinical isolates of Actinomyces spp. were examined for the presence of the gene encoding AmdR, a proposed global regulator of iron-dependent gene expression in A. oris. RESULTS: When A. oris was grown under iron-limiting conditions, the genes encoding iron/siderophore transporters fetA and sidD showed increased expression. One of these genes (sidD) was mutated, and the sidD::Km strain exhibited a 50% reduction in growth in late log and stationary phase cells in media that contained iron. This growth defect was restored when the sidD gene was provided in a complemented strain. We were able to isolate the AmdR-encoding gene in seven clinical isolates of Actinomyces. When these protein sequences were aligned to the laboratory strain, there was a high degree of sequence similarity. CONCLUSIONS: The growth of the sidD::Km mutant in iron-replete medium mirrored the growth of the wild-type strain grown in iron-limiting medium, suggesting that the sidD::Km mutant was compromised in iron uptake. The known iron regulator AmdR is well conserved in clinical isolates of A. oris. This work provides additional insight into iron metabolism in this important oral microbe.

Pyrazolopyridines as potent PDE4B inhibitors: 5-heterocycle SAR.

Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-α production from isolated human peripheral blood mononuclear cells.

Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors.

Optimisation of a high-throughput screening hit resulted in the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective inhibitors of Phosphodiesterase 4 (PDE4). Herein, we describe early SAR studies around this novel template highlighting preferred substituents and rationalization of SAR through X-ray crystal structures of analogues bound to the PDE4 active site. Pyrazolopyridine 20a was found to be a potent and selective PDE4 inhibitor which also inhibits LPS induced TNF-alpha production from isolated human peripheral blood mononuclear cells and has an encouraging rat PK profile suitable for oral dosing.

Do textbooks of clinical examination contain information regarding the assessment of critically ill patients?

We postulated that some of the reported deficiencies in trainee doctors' knowledge of acute care might be due to the quantity and quality of available information about the examination and clinical assessment of critically ill patients in commonly used medical textbooks. Using an agreed assessment system, 30 routinely available texts of clinical examination were reviewed. None of these contained a section devoted specifically to "assessing the critically ill patient" and few could be regarded as giving a comprehensive, systematic description of an assessment system suitable for use with the acutely ill. In general, descriptions of how to assess airway patency were rare, with only one describing how to differentiate partial from complete airway obstruction. Only four of the texts mentioned that measuring the respiratory rate would be useful in critically ill patients and the assessment of capillary refill time was poorly covered. Use of the AVPU scale to describe neurological status was found in only 3% of texts, and there was poor description of the clinical significance of hypotension, tachycardia, oliguria, hypothermia and pyrexia. We conclude that the current texts available to medical students and junior doctors do not provide sufficient information regarding the assessment of critically ill patients.