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Over the past 25 years, the World Heritage Committee has become progressively willing to overturn recommendations made by independent technical experts. While the Committee is the ultimate adjudicator on World Heritage listings, there has been a recent surge in decisions that actively depart from expert advice, resulting in a proliferation of decisions that are technically deficient and threaten the credibility of the World Heritage system.

Over the past 25 years, the World Heritage Committee has become progressively willing to overturn recommendations made by independent technical experts. While the Committee is the ultimate adjudicator on World Heritage listings, there has been a recent surge in decisions that actively depart from expert advice, resulting in a proliferation of decisions that are technically deficient and threaten the credibility of the World Heritage system. Advisory Body opinions that are pro-inscription are disproportionately upheld compared with opinions that do not recommend inscription and the most recent World Heritage meeting was almost entirely absent of any 'negative' outcome. The only exception to this was the Rosia Montana Mining Landscape in Romania, which was dually inscribed on the World Heritage List and In Danger List. This article uses the Rosia Montana Mining Landscape as a case study to demonstrate how the precedent of dual inscriptions has gone unchecked, allowing the World Heritage Committee to use diplomatic expertise to overshadow heritage knowledge, predominantly provided by the International Union for Conservation of Nature and the International Council on Monuments and Sites, to justify decisions. The consequence is that conservation is rapidly becoming irrelevant in the eyes of the Committee, with the World Heritage system serving as a vehicle for states to exclusively and indiscreetly prosecute their own political and parochial goals.

Over the past 25 years, the World Heritage Committee has become progressively willing to overturn recommendations made by independent technical experts. While the Committee is the ultimate adjudicator on World Heritage listings, there has been a recent surge in decisions that actively depart from expert advice, resulting in a proliferation of decisions that are technically deficient and threaten the credibility of the World Heritage system. Advisory Body opinions that are pro-inscription are disproportionately upheld compared with opinions that do not recommend inscription and the most recent World Heritage meeting was almost entirely absent of any 'negative' outcome. The only exception to this was the Roșia Montana Mining Landscape in Romania, which was dually inscribed on the World Heritage List and In Danger List. This article uses the Roșia Montana Mining Landscape as a case study to demonstrate how the precedent of dual inscriptions has gone unchecked, allowing the World Heritage Committee to use diplomatic expertise to overshadow heritage knowledge, predominantly provided by the International Union for Conservation of Nature and the International Council on Monuments and Sites, to justify decisions. The consequence is that conservation is rapidly becoming irrelevant in the eyes of the Committee, with the World Heritage system serving as a vehicle for states to exclusively and indiscreetly prosecute their own political and parochial goals.

The rate of cell growth is crucial for bacterial fitness and drives the allocation of bacterial resources, affecting, for example, the expression levels of proteins dedicated to metabolism and biosynthesis 1 , 2 . It is unclear, however, what ultimately determines growth rates in different environmental conditions. Moreover, increasing evidence suggests that other objectives are also important 3 – 7 , such as the rate of physiological adaptation to changing environments 8 , 9 . A common challenge for cells is that these objectives cannot be independently optimized, and maximizing one often reduces another. Many such trade-offs have indeed been hypothesized on the basis of qualitative correlative studies 8 – 11 . Here we report a trade-off between steady-state growth rate and physiological adaptability in Escherichia coli , observed when a growing culture is abruptly shifted from a preferred carbon source such as glucose to fermentation products such as acetate. These metabolic transitions, common for enteric bacteria, are often accompanied by multi-hour lags before growth resumes. Metabolomic analysis reveals that long lags result from the depletion of key metabolites that follows the sudden reversal in the central carbon flux owing to the imposed nutrient shifts. A model of sequential flux limitation not only explains the observed trade-off between growth and adaptability, but also allows quantitative predictions regarding the universal occurrence of such tradeoffs, based on the opposing enzyme requirements of glycolysis versus gluconeogenesis. We validate these predictions experimentally for many different nutrient shifts in E. coli , as well as for other respiro-fermentative microorganisms, including Bacillus subtilis and Saccharomyces cerevisiae . A model of sequential flux bottlenecks explains a universal trade-off between steady-state growth and physiological adaptation time in bacteria exposed to fluctuating growth conditions.

The COVID-19 pandemic has dramatically impacted cancer care worldwide. Disruptions have been seen across all facets of care. While the long-term impact of COVID-19 remains unclear, the immediate impacts on patients, their carers and the healthcare workforce are increasingly evident. This study describes disruptions and reorganisation of cancer services in Australia since the onset of COVID-19, from the perspectives of people affected by cancer and healthcare workers. Two separate online cross-sectional surveys were completed by: a) cancer patients, survivors, carers, family members or friends (n = 852) and b) healthcare workers (n = 150). Descriptive analyses of quantitative survey data were conducted, followed by inductive thematic content analyses of qualitative survey responses relating to cancer care disruption and perceptions of telehealth. Overall, 42% of cancer patients and survivors reported experiencing some level of care disruption. A further 43% of healthcare workers reported atypical delays in delivering cancer care, and 50% agreed that patient access to research and clinical trials had been reduced. Almost three quarters (73%) of patients and carers reported using telehealth following the onset of COVID-19, with high overall satisfaction. However, gaps were identified in provision of psychological support and 20% of participants reported that they were unlikely to use telehealth again. The reorganisation of cancer care increased the psychological and practical burden on carers, with hospital visitation restrictions and appointment changes reducing their ability to provide essential support. COVID-19 has exacerbated a stressful and uncertain time for people affected by cancer and healthcare workers. Service reconfiguration and the adoption of telehealth have been essential adaptations for the pandemic response, offering long-term value. However, our findings highlight the need to better integrate psychosocial support and the important role of carers into evolving pandemic response measures. Learnings from this study could inform service improvements that would benefit patients and carers longer-term.

Zircon crystals from the Jack Hills, Western Australia, are one of the few surviving mineralogical records of Earth’s first 500 million years and have been proposed to contain a paleomagnetic record of the Hadean geodynamo. A prerequisite for the preservation of Hadean magnetization is the presence of primary magnetic inclusions within pristine igneous zircon. To date no images of the magnetic recorders within ancient zircon have been presented. Here we use high-resolution transmission electron microscopy to demonstrate that all observed inclusions are secondary features formed via two distinct mechanisms. Magnetite is produced via a pipe-diffusion mechanism whereby iron diffuses into radiation-damaged zircon along the cores of dislocations and is precipitated inside nanopores and also during low-temperature recrystallization of radiation-damaged zircon in the presence of an aqueous fluid. Although these magnetites can be recognized as secondary using transmission electron microscopy, they otherwise occur in regions that are indistinguishable from pristine igneous zircon and carry remanent magnetization that postdates the crystallization age by at least several hundred million years. Without microscopic evidence ruling out secondary magnetite, the paleomagnetic case for a Hadean–Eoarchean geodynamo cannot yet been made.

Childhood abuse represents one of the most potent risk factors for the development of psychopathology during childhood, accounting for 30–60% of the risk for onset. While previous studies have separately associated reductions in gray matter volume (GMV) with childhood abuse and internalizing psychopathology (IP), it is unclear whether abuse and IP differ in their structural abnormalities, and which GMV features are related to abuse and IP at the individual level. In a pooled multisite, multi-investigator sample, 246 child and adolescent females between the ages of 8–18 were recruited into studies of interpersonal violence (IPV) and/or IP (i.e. posttraumatic stress disorder (PTSD), depression, and/or anxiety). Youth completed assessments for IP, childhood abuse history, and underwent high resolution T1 structural MRI. First, we characterized how differences in GMV associated with childhood abuse exposure depend on the presence or absence of IP using voxel-based morphometry (VBM). Next, we trained convolutional neural networks to predict individual psychopathology and abuse experience and estimated the strength and direction of importance of each structural feature in making individual-level predictions using Shapley values. Shapley values were aggregated across the entire cohort, and the top 1% of feature clusters with the highest importance are reported. At a group-level, VBM analyses identified widespread decreases in GMV across the prefrontal cortex, insula, and hippocampus in youth with IP, while abuse experience was specifically associated with increased GMV in the cingulate cortex and supramarginal gyrus. Further, interactions between IP and severity of abuse were identified in the ventral and dorsal prefrontal cortex, anterior cingulate cortex, and thalamus. After extensive training, model tuning, and model evaluation, the neural networks performed above chance when predicting IP (63% accuracy) and abuse experiences (71% accuracy) at the level of the individual. Interestingly, structural regions with the highest importance in making individual IP predictions had a high degree of overlap with group-level patterns. We have identified unique structural correlates of childhood abuse and IP on both the group and individual level with a high degree of overlap, providing evidence that IP and trauma exposure may uniquely and jointly impact child and adolescent structural neurodevelopment. Feature learning may offer power and novelty above and beyond traditional group-level approaches to the identification of biomarkers and a movement towards individualized diagnosis and treatment.

IntroductionHuman T-cell lymphotropic virus type-1 (HTLV-1) infection remains asymptomatic in >90% of the 20-million people infected worldwide. However in 3%, chronic inflammation within the thoracic spinal cord leads to progressive spastic paraparesis; HTLV-1 associated myelopathy (HAM). This pathological process is not limited to the thoracic cord. We present a case of HTLV-1 encephalomyelitis.CaseA 53-year-old woman with HAM of 9 years duration presented with subacute cerebellar dysfunc- tion, being unable to feed herself, 3-months after cessation of methotrexate. Investigations demonstrated extensive T2-hyperintensity within the brainstem, cortical and subcortical white matter with punctate contrast enhancement; lymphocytic CSF; and high blood (36%) and CSF (72%) HTLV-1 proviral load (DNA copies per 100 lymphocytes). We diagnosed HTLV-1 encephalomyelitis and commenced high dose methylprednisolone with slow steroid taper following which functional independence in the upper limbs was regained.DiscussionRisk of HAM rises exponentially once HTLV-1 proviral load exceeds 1%, while CSF:blood proviral load ratio ≥2:1 indicates CNS infiltration of HTLV-1 infected lymphocytes. This patient’s high HTLV-1 proviral load and widespread MRI changes indicated HTLV-1 associated inflammation of the brain and spine. Prompt immunosuppression resulted in significant recovery and highlights the importance of early rec- ognition and management of extraspinal manifestations of HTLV-1 infection.j.king-robson@nhs.net

The results of this large study involving more than 64,500 U.S. women in the general population and 28 genes that have been previously implicated in conferring risk of breast cancer (when variant) have implications for the interpretation of results obtained by multigene panel testing.

Polyhedral models of metabolic networks are computationally tractable and can predict some cellular functions. A longstanding challenge is incorporating metabolites without losing tractability. In this paper, we do so using a new second-order cone representation of the Michaelis-Menten kinetics. The resulting model consists of linear stoichiometric constraints alongside second-order cone constraints that couple the reaction fluxes to metabolite concentrations. We formulate several new problems around this model: conic flux balance analysis, which augments flux balance analysis with metabolite concentrations; dynamic conic flux balance analysis; and finding minimal cut sets of networks with both reactions and metabolites. Solving these problems yields information about both fluxes and metabolite concentrations. They are second-order cone or mixed-integer second-order cone programs, which, while not as tractable as their linear counterparts, can nonetheless be solved at practical scales using existing software.