Explore the vast range of titles available.

Background Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. Methods Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. Discussion This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. Trial registration Trial registered on Australian New Zealand Clinical Trials Registry. Registration number: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true

Non-small cell lung cancer (NSCLC) metastatic to the brain leptomeninges is rapidly fatal, cannot be biopsied, and cancer cells in the cerebrospinal fluid (CSF) are few; therefore, available tissue samples to develop effective treatments are severely limited. This study aimed to converge single-cell RNA-seq and cell-free RNA (cfRNA) analyses to both diagnose NSCLC leptomeningeal metastases (LM), and to use gene expression profiles to understand progression mechanisms of NSCLC in the brain leptomeninges. NSCLC patients with suspected LM underwent withdrawal of CSF via lumbar puncture. Four cytology-positive CSF samples underwent single-cell capture ( n  = 197 cells) by microfluidic chip. Using robust principal component analyses, NSCLC LM cell gene expression was compared to immune cells. Massively parallel qPCR (9216 simultaneous reactions) on human CSF cfRNA samples compared the relative gene expression of patients with NSCLC LM ( n  = 14) to non-tumor controls ( n  = 7). The NSCLC-associated gene, CEACAM6 , underwent in vitro validation in NSCLC cell lines for involvement in pathologic behaviors characteristic of LM. NSCLC LM gene expression revealed by single-cell RNA-seq was also reflected in CSF cfRNA of cytology-positive patients. Tumor-associated cfRNA (e.g., CEACAM6 , MUC1 ) was present in NSCLC LM patients’ CSF, but not in controls ( CEACAM6 detection sensitivity 88.24% and specificity 100%). Cell migration in NSCLC cell lines was directly proportional to CEACAM6 expression, suggesting a role in disease progression. NSCLC-associated cfRNA is detectable in the CSF of patients with LM, and corresponds to the gene expression profile of NSCLC LM cells. CEACAM6 contributes significantly to NSCLC migration, a hallmark of LM pathophysiology.

Biological invasions by woody species in forested ecosystems can have significant impacts on forest management and conservation. We designed and tested several management options based on the physiology of Chinese tallow (Triadica sebifera [L.] Small). Specifically, we tested four treatments, including mastication, foliar herbicide, and fire (MHfolF), mastication and foliar herbicide (MHfol), dormant-stem herbicide and fire (HdorF), and dormant-stem herbicide (Hdor), to determine their efficacy in reducing the density and regeneration of this highly invasive tree species. Mastication treatments were significant in reducing density the first year but not after 3 years. Prescribed fire significantly reduced density combined with previous treatments. Regeneration coverage was highest on those sites with mastication, which was not affected by the addition of prescribed fire. Overall, we found that the most comprehensive treatment (MHfolF) was more effective in reducing density but did not result in a difference in the amount of regeneration after treatment. Management and Policy Implications Chinese tallow is a highly invasive tree species in the southeastern coastal plain, USA. Chinese tallow invasions can displace native species, potentially having substantial economic impacts on timber resources and desirable forest diversity. Attempts to manage and control Chinese tallow with single treatments are often only temporarily effective because of its ability to regenerate from a persistent seed bank and by root and stump sprouting. In this study, we developed and tested a multiple-treatment regime using mastication and herbicide treatments followed by prescribed burning to reestablish this important ecological process. Individual treatments were timed and sequenced to reduce Chinese tallow densities when they were physiologically most susceptible to further limit their regrowth and new seedling establishment. Long-term control will require additional burning or treatments before seedlings escape to larger size classes. Therefore, effective management of Chinese tallow requires a forward-thinking, integrated approach that aims not only to reduce or exclude the invader but also to restore the affected community by building resistance to future invasion. Furthermore, in the selection of invasive species management practices, the prevention of future invasion must be considered because management actions themselves are disturbance events and many invasive species thrive in disturbed environments.

Abstract INTRODUCTION CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) administers non-isometric, conformational high-dose radiation to the root entry zone, with possible post-procedural numbness from excessive brainstem exposure. We evaluated outcomes from two treatment plans differing in their maximum brainstem dose. METHODS A retrospective, single-institution review of 91 TGN patients treated with CyberKnife from January 2005-May 2007 (Plan A, N = 47) and January 2009-August 2013 (Plan B, N = 44) was conducted. Plan A (vs B) aimed for a maximum brainstem dose of 40 vs 25 Gy, respectively, both in one fraction with 75 Gy to the 100% isodose line. Primary outcome was self-reported pain control. Secondary outcomes included change in Barrow Neurologic Institute (BNI) pain and numbness scores. Pre-pontine nerve length, maximum brainstem dose, and treatment history were additionally recorded for their predictive contribution by matched-cohort regression. RESULTS >Patients were followed for a mean of 23 months, and 62% were naiuml;ve to treatment. Plans A and B exhibited treatment failure, durable improvement, and pain recurrence in 6.4% vs 18.0% (P = 0.084), 68.1% vs 36.4% (P = 0.002), and 25.5% vs 45.5% (P = 0.047), respectively. Mean BNI pain scores improved for 74.5% vs 61.3% (P = 0.18), while BNI numbness scores increased for 45.2% and 72.7% (P = 0.042). Cohorts differed in baseline nerve length at 10.1 mm vs 7.5 mm (P < 0.001). Regression analysis on cohorts matched by length demonstrated that treatment plans allowing higher brainstem maximum dosing was associated with pain improvement (P = 0.05), and univariate analyses showing longer nerve length predicted decreased numbness (P = 0.03). Furthermore, under Plan A, improvement was predicted by age, prior decompression and prior SRS (AUC = 0.82). CONCLUSION These outcomes show a higher maximum brainstem dose constraint may result in better pain control without worsening rates of facial numbness. Future application of CyberKnife SRS may consider higher doses in patients with longer nerves and no prior treatment history.

Biological invasions by woody species in forested ecosystems can have significant impacts on forest management and conservation. We designed and tested several management options based on the physiology of Chinese tallow (Triadica sebifera [L.] Small). Specifically, we tested four treatments, including mastication, foliar herbicide, and fire (MHfolF), mastication and foliar herbicide (MHfol), dormant-stem herbicide and fire (HdorF), and dormant-stem herbicide (Hdor), to determine their efficacy in reducing the density and regeneration of this highly invasive tree species. Mastication treatments were significant in reducing density the first year but not after 3 years. Prescribed fire significantly reduced density combined with previous treatments. Regeneration coverage was highest on those sites with mastication, which was not affected by the addition of prescribed fire. Overall, we found that the most comprehensive treatment (MHfolF) was more effective in reducing density but did not result in a difference in the amount of regeneration after treatment.

Three prehistoric sites in the Upper Mun River Valley of north-eastern Thailand have provided a detailed chronological succession comprising 12 occupation phases. These represent occupation spanning 2300 years, from initial settlement in the Neolithic (seventeenth century BC) through to the Iron Age, ending in the seventh century AD with the foundation of early states. The precise chronology in place in the Upper Mun River Valley makes it possible to examine changes in social organisation, technology, agriculture and demography against a background of climatic change. In this area the evidence for subsistence has been traditionally drawn from the biological remains recovered from occupation and mortuary contexts. This paper presents the results of carbon isotope analysis to identify and explain changes in subsistence over time and between sites, before comparing the results with two sites of the Sakon Nakhon Basin, located 230km to the north-east, to explore the possibility of regional differences.

Within 1-2 decades, quantum computers are expected to obsolesce current public-key cryptography, driving authorities such as IETF and NIST to push for adopting quantum-resistant cryptography (QRC) in ecosystems like Internet Protocol Security (IPsec). However, IPsec struggles to adopt QRC, primarily due to the limited ability of Internet Key Exchange Protocol Version 2 (IKEv2), which establishes IPsec connections, to tolerate the large public keys and digital signatures of QRC. Many solutions (e.g., IETF RFCs) are proposed to integrate QRC into IKEv2, but remain largely untested in practice. In this paper, we measure the performance of these proposals over the Internet by designing and implementing a novel, scalable, and flexible testbed for quantum-resistant IPsec, and we expose the serious shortcomings of existing proposals for quantum-resistant IKEv2 when deployed in constrained (e.g., lossy, rate-limited) networks. Through experimental deployments ranging from cloud-based virtual networks to hardware-in-the-loop wireless links between software-defined radios, as well as deployment on the international FABRIC testbed for next-generation networks, we show that today's solutions for quantum-resistant IPsec are insufficient, necessitating development of better approaches.

[Sue Cathcart] and [Steve] embarked on their lifelong habit of restoring old houses. They moved into the ancient Poet's Cottage, in Hurstpierpoint, West Sussex, and then into a nearby rundown Victorian semi. While Steve worked with troubled families at a local residential centre, Sue cared for her widowed father as well as their three children, Saul, Simon and Helen. Her restless, creative spirit led her to fit in a City & Guilds course and set up Rooks' Wood workshop, where she offered classes to all-comers in the design and renovation of clothing and furniture.