Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients

<p>Abstract</p> <p>Background</p> <p>Sensorineural hearing loss (SNHL) is one of the major long term side effects from radiation therapy (RT) in nasopharyngeal cancer (NPC) patients. This study aims to review the incidences of SNHL when treating with different radiation techniques. The additional objective is to determine the relationship of the SNHL with the radiation doses delivered to the inner ear.</p> <p>Methods</p> <p>A retrospective cohort study of 134 individual ears from 68 NPC patients, treated with conventional RT and IMRT in combination with chemotherapy from 2004-2008 was performed. Dosimetric data of the cochlea were analyzed. Significant SNHL was defined as > 15 dB increase in bone conduction threshold at 4 kHz and PTA (pure tone average of 0.5, 1, 2 kHz). Relative risk (RR) was used to determine the associated factors with the hearing threshold changes at 4 kHz and PTA.</p> <p>Results</p> <p>Median audiological follow up time was 14 months. The incidence of high frequency (4 kHz) SNHL was 44% for the whole group (48.75% in the conventional RT, 37% with IMRT). Internal auditory canal mean dose of > 50 Gy had shown a trend to increase the risk of high frequency SNHL (RR 2.02 with 95% CI 1.01-4.03, p = 0.047).</p> <p>Conclusion</p> <p>IMRT and radiation dose limitation to the inner ear appeared to decrease SNHL.</p

Target 2035-update on the quest for a probe for every protein

Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. The challenge of translating the wealth of new knowledge from genomics into new medicines is that proteins, and not genes, are the primary executers of biological function. Therefore, much of how biology works in health and disease must be understood through the lens of protein function. Accordingly, a subset of human proteins has been at the heart of research interests of scientists over the centuries, and we have accumulated varying degrees of knowledge about approximately 65% of the human proteome. Nevertheless, a large proportion of proteins in the human proteome (∼35%) remains uncharacterized, and less than 5% of the human proteome has been successfully targeted for drug discovery. This highlights the profound disconnect between our abilities to obtain genetic information and subsequent development of effective medicines. Target 2035 is an international federation of biomedical scientists from the public and private sectors, which aims to address this gap by developing and applying new technologies to create by year 2035 chemogenomic libraries, chemical probes, and/or biological probes for the entire human proteome

Tremor in multiple sclerosis

Tremor is estimated to occur in about 25 to 60 percent of patients with multiple sclerosis (MS). This symptom, which can be severely disabling and embarrassing for patients, is difficult to manage. Isoniazid in high doses, carbamazepine, propranolol and gluthetimide have been reported to provide some relief, but published evidence of effectiveness is very limited. Most trials were of small size and of short duration. Cannabinoids appear ineffective. Tremor reduction can be obtained with stereotactic thalamotomy or thalamic stimulation. However, the studies were small and information on long-term functional outcome is scarce. Physiotherapy, tremor reducing orthoses, and limb cooling can achieve some functional improvement. Tremor in MS remains a significant challenge and unmet need, requiring further basic and clinical research

Drift as a Force of Evolution: A Manipulationist Account

Can evolutionary theory be properly characterised as a “theory of forces”, like Newtonian mechanics? One common criticism to this claim concerns the possibility to conceive genetic drift as a causal process endowed by a specific magnitude and direction. In this article, we aim to offer an original response to this criticism by pointing out a connection between the notion of force and the notion of explanatory depth, as depicted in Hitchcock and Woodward’s manipulationist account of causal explanation. In a nutshell, our argument is that, since force-explanations can be consistently reframed as deep explanations and vice versa, and the notion of drift can be characterised in manipulationist terms as constitutively intervening in evolutionary deep explanations, then drift-explanations can be consistently reframed as force-explanations, and drift can be properly considered as a force of evolution. Insofar as similar considerations may be extended also to other evolutionary factors – chiefly selection –, our analysis offers an important support to the claim that evolutionary theory is a theory of forces.info:eu-repo/semantics/publishedVersio

Monsters: interdisciplinary explorations in monstrosity

There is a continued fascination with all things monster. This is partly due to the popular reception of Mary Shelley’s Monster, termed a “new species” by its overreaching but admiringly determined maker Victor Frankenstein in the eponymous novel first published in 1818. The enduring impact of Shelley’s novel, which spans a plethora of subjects and genres in imagery and themes, raises questions of origin and identity, death, birth and family relationships as well as the contradictory qualities of the monster. Monsters serve as metaphors for anxieties of aberration and innovation. Stephen Asma (2009) notes that monsters represent evil or moral transgression and each epoch, to speak with Michel Foucault, evidences a “particular type of monster” (2003, 66). Academic debates tend to explore how social and cultural threats come to be embodied in the figure of a monster and their actions literalize our deepest fears. Monsters in contemporary culture, however, have become are more humane than ever before. Monsters are strong, resilient, creative and sly creatures. Through their playful and invigorating energy they can be seen to disrupt and unsettle. They still cater to the appetite for horror, but they also encourage us to feel empathy. The encounter with a monster can enable us to stop, wonder and change our attitudes towards technology and our body and each other. This commentary article considers the use of the concepts of ‘monsters’ or ‘monstrosity’ in literature, contemporary research, culture and teaching contexts at the intersection of the Humanities and the Social Sciences

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Donated chemical probes for open science.

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project