To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is hindered by significant weight gain. A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data.
The OLZ/SAM development program consists of 18 phase 1–3 clinical studies evaluating antipsychotic and weight mitigation efficacy of OLZ/SAM, along with pharmacokinetics, safety, and tolerability. Safety evaluation also included metabolic laboratory assessments.
OLZ/SAM significantly improved psychotic symptoms (measured by Positive and Negative Syndrome Scale); improvements were similar to that observed with olanzapine vs placebo. OLZ/SAM resulted in significantly less weight gain than olanzapine. Additionally, 2 long-term phase 3 extension studies confirmed the durability of antipsychotic effect, as well as stabilization of weight and metabolic parameters in those continuing treatment. Supporting the potential use of OLZ/SAM in BD-I, OLZ/SAM or olanzapine resulted in bioequivalent olanzapine plasma concentrations, and OLZ/SAM did not affect lithium or valproate pharmacokinetics. OLZ/SAM treatment had no clinically relevant effects on ECG parameters (including QTc interval). OLZ/SAM and olanzapine safety were similar, except for reduced weight gain with OLZ/SAM; no additional safety risks were identified.
Data across 18 OLZ/SAM studies in >1600 subjects support an antipsychotic efficacy and safety profile for OLZ/SAM that is similar to olanzapine, with significantly less weight gain than olanzapine. OLZ/SAM is a potential new treatment for schizophrenia and BD-I patients needing efficacious long-term treatment with reduced risk of weight gain.
Reward Deficiency Syndrome (RDS) is an umbrella term for all drug and nondrug addictive behaviors, due to a dopamine deficiency, “hypodopaminergia.” There is an opioid-overdose epidemic in the USA, which may result in or worsen RDS. A paradigm shift is needed to combat a system that is not working. This shift involves the recognition of dopamine homeostasis as the ultimate treatment of RDS via precision, genetically guided KB220 variants, called Precision Behavioral Management (PBM). Recognition of RDS as an endophenotype and an umbrella term in the future DSM 6, following the Research Domain Criteria (RDoC), would assist in shifting this paradigm.
A combination of olanzapine and samidorphan (OLZ/SAM) is in development for schizophrenia to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The objective of this phase 1 exploratory study was to assess metabolic treatment effects of OLZ/SAM.
Healthy, non-obese adults (18–40 years) were randomized 2:2:1 to once-daily OLZ/SAM, olanzapine, or placebo for 21 days. Assessments included oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, weight gain, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance.
Sixty subjects were randomized (OLZ/SAM, n=24; olanzapine, n=24; placebo, n=12); 19 (79.2%), 22 (91.7%), and 11 (91.7%), respectively, completed the study. In the OGTT, olanzapine led to significant hyperinsulinemia (P<0.0001) and significantly reduced insulin sensitivity (2-hour Matsuda index) at day 19 vs baseline (P=0.0012), changes not observed with OLZ/SAM. No significant between-group differences were observed for change from baseline in clamp-derived insulin sensitivity index at day 21. Least squares mean weight change from baseline was similar with OLZ/SAM (3.16 kg) and olanzapine (2.87 kg); both were significantly higher than placebo (0.57 kg; both P<0.01). Caloric intake significantly decreased from baseline to day 22 with OLZ/SAM (P=0.015) but not with olanzapine or placebo. Forty-nine subjects (81.7%) experienced ≥1 AE (OLZ/SAM, 87.5%; olanzapine, 79.2%; placebo, 75.0%).
In this exploratory study, hyperinsulinemia and decreased insulin sensitivity were observed in the OGTT with olanzapine but not with OLZ/SAM or placebo. Clamp-derived insulin sensitivity index and weight changes were similar with OLZ/SAM and olanzapine in healthy subjects during the 3-week study.
Colorectal cancer (CRC) is the fourth most common cancer in the UK; 95% of CRCs develop from colorectal adenomas. Adults in England aged 60–74 years are screened for colorectal cancer through the national Bowel Cancer Screening Programme (BCSP) which aims to detect colorectal cancer early, and also remove colorectal adenomas. However, adenoma recurrence is common. The World Cancer Research Fund (WCRF) estimates that around 45% of CRC cases could be prevented by a healthy lifestyle. There are no specific dietary guidelines to protect against adenoma recurrence and patients do not receive dietary advice in the care pathway. Nonetheless understanding the dietary intake of people with adenoma who are at high-risk of developing CRC and their subsequent dietary behaviour post-diagnosis may design future intervention strategies.
This study aims to describe the diet of colorectal adenoma patients and evaluate whether there were elective changes in diet following diagnosis.
The data used in this study were obtained from colorectal adenoma patients at high risk of recurrence, recruited to the seAFOod polyp prevention trial through the English BCSP. Dietary intake was assessed using the EPIC Food Frequency Questionnaire at two time points: during the 12 months before and during the 12 months after adenoma diagnosis. FETA dietary analysis software was used to extract data. Paired Sample-T-Tests and Wilcoxon Signed-Rank Test were used to assess change in intake using SPSS version 25.
Of the 709 patients recruited to the main study, 526 completed the FFQ on both occasions, of whom 81.7% were males. The mean age was 65 years (SD 4.8), 83.4% were overweight or obese with mean BMI = 29.5 kg/m2 (SD 5.7). The majority of nutrient intakes met UK DRVs, with the exception of low intake of fibre, vitamin D and selenium. Following diagnosis, a significant reduction was detected in daily intake of energy (from 7.7 to 7.5 MJ, p < 0.05) meat and meat products (from 124 to 111 g, p < 0.005), non-alcoholic beverages (from 939 to 898 g, p < 0.05) and nuts (from 5.5 to 4.3 g, p < 0.05). Subgroup analysis revealed that dietary changes were confined to men where the reduction in energy was by 293 kj/day and in meat by 1.5 portions per week.
Patients do modify diet following a diagnosis of adenoma and changes correspond to WCRF healthy diet guidelines. Whether detected difference between males and females was due to the sample size or due to actual difference in behavior is not clear.
The SUPEREDEN3 study, a phase II randomized controlled trial, suggests that social recovery therapy (SRT) is useful in improving functional outcomes in people with first episode psychosis. SRT incorporates cognitive behavioural therapy (CBT) techniques with case management and employment support, and therefore has a different emphasis to traditional CBT for psychosis, requiring a new adherence tool.
This paper describes the SRT adherence checklist and content of the therapy delivered in the SUPEREDEN3 trial, outlining the frequency of SRT techniques and proportion of participants who received a full therapy dose. It was hypothesized that behavioural techniques would be used frequently, consistent with the behavioural emphasis of SRT.
Research therapists completed an adherence checklist after each therapy session, endorsing elements of SRT present. Data from 1236 therapy sessions were reviewed to determine whether participants received full, partial or no therapy dose.
Of the 75 participants randomized to receive SRT, 57.3% received a full dose, 24% a partial dose, and 18.7% received no dose. Behavioural techniques were endorsed in 50.5% of sessions, with cognitive techniques endorsed in 34.9% of sessions.
This report describes an adherence checklist which should be used when delivering SRT in both research and clinical practice. As hypothesized, behavioural techniques were a prominent feature of the SRT delivered in SUPEREDEN3, consistent with the behavioural emphasis of the approach. The use of this adherence tool would be considered essential for anyone delivering SRT looking to ensure adherence to the model.
The triazines are one of the most widely used herbicide classes ever developed and are critical for managing weed populations that have developed herbicide resistance. These herbicides are traditionally valued for their residual weed control in more than 50 crops. Scientific literature suggests that atrazine, and perhaps other s-triazines, may no longer remain persistent in soils due to enhanced microbial degradation. Experiments examined the rate of degradation of atrazine and two other triazine herbicides, simazine and metribuzin, in both atrazine-adapted and non-history Corn Belt soils, with similar soils being used from each state as a comparison of potential triazine degradation. In three soils with no history of atrazine use, the t1/2 of atrazine was at least four times greater than in three soils with a history of atrazine use. Simazine degradation in the same three sets of soils was 2.4 to 15 times more rapid in history soils than non-history soils. Metribuzin in history soils degraded at 0.6, 0.9, and 1.9 times the rate seen in the same three non-history soils. These results indicate enhanced degradation of the symmetrical triazine simazine, but not of the asymmetrical triazine metribuzin.
Soiling in solar power generation will be a significant obstacle to its growth if a water free method cannot be found. Demand for water in arid regions will increase as more solar power generation is built, requiring more water to clean the optical surface, in turn increasing the price of water. This will lead to increased operating costs for solar power generation, and potentially disputes in locations where water is scarce. The electrodynamic screen (EDS) can reduce soiling and contribute to restoring the optical surface without the use of water. Periodic cleaning will still be required, but at reduced frequency, leading to a significant reduction in the consumption of water. In this model, it was found that a 250 MW concentrated solar power plant would have a 74% reduction in water given current laboratory production uncertainties. This indicates that EDS technology could decrease both the operating cost and the water use for solar generation plants.
The review article describes the composition, working, and benefits of the electrodynamic screen (EDS) film, a self-cleaning surface technology that can be retrofitted onto solar and thermal energy collectors. The EDS film avoids the use of water and robotic parts that are the common cleaning techniques used in solar/thermal power plants and thus emerges as a viable and scalable solution to the soiling problem faced recurrently by these plants. The article summarizes different experiments conducted to improve the efficiency of the EDS film in terms of reflectivity and performance. Field test results are also included to underscore the success of the EDS film operation.
Dust build-up or soiling on thermal and solar energy collector surfaces is a major problem and its cleaning is a major issue for solar energy conversion. Here, a self-cleaning technology is described as a scalable and viable solution to clear the surfaces. EDS film technology does not require water, manual labor, or moving parts to function, and the power needed to operate EDS is almost negligible and can be derived from the harvesting device itself. The EDS films thereby help mitigate the energy loss caused by soiling in solar and thermal harvesting systems. An EDS film with reflective or transparent electrodes can be retrofitted on concentrated solar power mirrors and on photovoltaic (PV) panels to sustain and aid their unhindered reflection and absorption of incident sunlight, respectively. We report experiments and describe methods used to increase the reflectivity of the electrodes of an EDS film. Results obtained from lab test setups and field test units that define the functionality, reflectivity, and stability of the electrodes on the EDS films are also presented. Field test results that compare and report the performance of PV panel output current over long periods of testing, with and without EDS films are also discussed. Test results from 3-month outdoor testing, which demonstrate recovery back to >95% of the pristine system, after decrease to 80–90% before EDS film activation, are also shown.
A 2,4-D-resistant tall waterhemp population (FS) from Nebraska was evaluated for resistance to other TIR1 auxin receptor herbicides and to herbicides having alternative mechanisms of action using greenhouse bioassays and genetic markers. Atrazine, imazethapyr, lactofen, mesotrione, glufosinate, and glyphosate were applied in a single-dose bioassay, and tissue was collected from marked plants for genetic analysis. The FS population was not injured by atrazine or by imazethapyr. Approximately 50% of the plants survived lactofen and were actively growing 28 d after treatment. The population was susceptible to mesotrione, glufosinate, and glyphosate. Ametryn, chlorimuron-ethyl, 2,4-D, aminocyclopyraclor, aminopyralid, and picloram were applied in dose–response studies. The FS population was sensitive to ametryn, and the Ser-264-Gly substitution in the D1 protein was not detected, suggesting the lack of response to atrazine is not due to a target-site mutation. The FS population exhibited less than 50% injury to chlorimuron-ethyl at application rates 20 times the labeled use rate. The Ser-653-Asn acetolactate synthase (ALS) substitution, which confers resistance to imidazolinone herbicides, was present in the FS population. However, this does not explain the lack of response to the sulfonylurea herbicide, chlorimuron-ethyl. Sequencing of a portion of the PPX2L gene did not show the ΔG210 mutation that confers resistance to protoporphyrinogen oxidase–inhibiting herbicides, suggesting that other factors were responsible for waterhemp survival after lactofen application. The FS population was confirmed to be at least 30-fold resistant to 2,4-D relative to the susceptible populations. In addition, it was at least 3-fold less sensitive to aminopyralid and picloram, two other TIR1 auxin receptor herbicides, than the 2,4-D-susceptible populations were. These data indicated that the FS population contains both target and non–target site mechanisms conferring resistance to herbicides spanning at least three mechanisms of action: TIR1 auxin receptors, ALS inhibitors, and photosystem II inhibitors.
The supply of soil resources is critical for the establishment and long-term competitive success of a plant species. Although there is considerable research on the effects of water supply on crop growth and productivity, there is little published research on the comparative response of crops and weeds to limiting soil water supply. The objective of this research was to determine the growth and transpiration efficiency of corn and velvetleaf at three levels of water supply. One corn or velvetleaf plant was grown in a large pot lined with plastic bags. When seedlings reached 10 cm, bags were sealed around the base of the plant, so the only water loss was from transpiration. Daily transpiration was measured by weighing the pots at the same time each day. The experiment was conducted in the fall of 2007 and in the spring of 2008. Four replicates of each species–water treatment were harvested periodically to determine biomass accumulation and leaf area. The relationship between cumulative aboveground biomass and water transpired was described using a linear function in which the slope defined the transpiration efficiency (TE). Corn TE was greater than velvetleaf TE in all treatments during both trials. In the fall trial, corn TE was 6.3 g kg–1, 47% greater than that of velvetleaf TE. In the spring trial, TEs of both species were lower overall, and corn TE increased with declining water supply. Corn produced more biomass and leaf area than velvetleaf did at all water-supply levels. Velvetleaf partitioned more biomass to roots compared with shoots during early growth than corn did. The ability of corn to generate more leaf area and its investment in a greater proportion of biomass into root growth at all levels of water supply may enable it to more-effectively avoid velvetleaf interference under all levels of soil-water supply.
Cathars have long been regarded as posing the most organised challenge to orthodox Catholicism in the medieval West, even as a "counter-Church" to orthodoxy in southern France and northern Italy. Their beliefs, understood to be inspired by Balkan dualism, are often seen as the most radical among medieval heresies. However, recent work has fiercely challenged this paradigm, arguing instead that "Catharism" was a construct of its persecutors, mis-named and mis-represented by generations of subsequent scholarship, and its supposedly radical views were a fantastical projection of the fears of orthodox commentators. This volume brings together a wide range of views from some of the most distinguished international scholars in the field, in order to address the debate directly while also opening up new areas for research. Focussing on dualism and anti-materialist beliefs in southern France, Italy and the Balkans, it considers a number of crucial issues. These include: what constitutes popular belief; how (and to what extent) societies of the past were based on the persecution of dissidents; and whether heresy can be seen as an invention of orthodoxy. At the same time, the essays shed new light on some key aspects of the political, cultural, religious and economic relationships between the Balkans and more western regions of Europe in the Middle Ages.
Antonio Sennis isSenior Lecturer in Medieval History at University College London Contributors: John H. Arnold, Peter Biller, Caterina Bruschi, David d'Avray, Jörg Feuchter, Bernard Hamilton, Robert I. Moore, MarkGregory Pegg, Rebecca Rist, Lucy Sackville, Antonio Sennis, Claire Taylor, Julien Théry-Astruc, Yuri Stoyanov
Many contemporary horror filmmakers pride themselves on violating taboos in their films, especially taboos concerning violence. However, there is a line that even many of the most hardened filmmakers refuse to cross: violence against animals. In fact, some horror filmmakers have spoken out against animal abuse. For instance, heavy metal musician-turned-horror filmmaker Rob Zombie, director of House of 1000 Corpses (2003), The Devil's Rejects (2005) and the remake of Halloween (2007), teamed up with the organisation People for the Ethical Treatment of Animals (PETA) in 2007 to record a message for their ‘Thanksgiving Hotline’, a ‘compassionate alternative’ to the Butterball Turkey Talk Line that offers tips on turkey preparation. Zombie is a self-described ‘ethical vegetarian’ and as such his contribution details the cruelty and mistreatment to which turkeys are subjected in Butterball's factory farms (PETA, 2007). In 2009 another horror filmmaker, Eli Roth, director of the Hostel films (2006–7), appeared in a promotional spot for PETA. More lighthearted than Zombie's message but no less serious, the promo features Roth being squeezed by a large snake puppet as he says to the camera: ‘While violence in the movies is make-believe, sadly violence against animals is all too real … So, let's leave the violence where it belongs: on the screen.’
Zombie's and Roth's attitudes towards animal violence differ significantly from those exhibited by Italian exploitation directors such as Umberto Lenzi, Ruggero Deodato and Sergio Martino. These filmmakers had an undeniable influence on contemporary horror filmmakers – especially Roth, who featured Deodato in a cameo in Hostel: Part II (2007), provided a video introduction for the 2011 DVD release of Martino's I corpi presentano tracce di violenza carnale/Torso (1973), and paid homage to the Italian cannibal sub-genre with his film The Green Inferno (2013). However, these Italian directors took an extremely different position on violence towards animals, as several of their films feature graphic footage of real animal torture, mutilation and death. The cycle of cannibal films made by Italian exploitation filmmakers lasted roughly from the early 1970s to the early 1980s and consists largely of what are undoubtedly some of the most controversial films in world cinema, depicting white Westerners confronted in the jungle by indigenous cannibalistic tribes.
Whether contact precautions (CP) are required to control the endemic transmission of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in acute care hospitals is controversial in light of improvements in hand hygiene, MRSA decolonization, environmental cleaning and disinfection, fomite elimination, and chlorhexidine bathing.
To provide a framework for decision making around use of CP for endemic MRSA and VRE based on a summary of evidence related to use of CP, including impact on patients and patient care processes, and current practices in use of CP for MRSA and VRE in US hospitals.
A literature review, a survey of Society for Healthcare Epidemiology of America Research Network members on use of CP, and a detailed examination of the experience of a convenience sample of hospitals not using CP for MRSA or VRE.
Hospital epidemiologists and infection prevention experts.
No high quality data support or reject use of CP for endemic MRSA or VRE. Our survey found more than 90% of responding hospitals currently use CP for MRSA and VRE, but approximately 60% are interested in using CP in a different manner. More than 30 US hospitals do not use CP for control of endemic MRSA or VRE.
Higher quality research on the benefits and harms of CP in the control of endemic MRSA and VRE is needed. Until more definitive data are available, the use of CP for endemic MRSA or VRE in acute care hospitals should be guided by local needs and resources.
Infect Control Hosp Epidemiol 2015;36(10):1163–1172
Soybean cyst nematode (SCN) is a major soybean yield–limiting disease in the United States. Henbit, a winter annual species common to no-till fields in the midwestern United States, is known to act as an alternative host for SCN. A simulation was performed to estimate how likely SCN was to reproduce on henbit roots during a 30-yr period in two important soybean production areas of Nebraska. Simulations were conducted using published information on henbit seedling emergence, SCN reproduction on henbit roots, and SCN response to soil temperature. Results indicate that SCN would be able to complete one generation on henbit roots under Nebraska conditions. The SCN reproductive cycle was not likely to be completed before the winter in south central Nebraska, but one SCN generation was predicted to be completed in the fall in 2 out of 30 simulation years (7% likelihood) in southeast Nebraska. Based on our predictions, to reduce the chances of SCN population build-up in the absence of its main host (soybean), weed management in fields infested with both henbit and SCN should be completed after crop harvest in the fall when most henbit seedlings have emerged and are growing but the SCN developing on henbit roots have not yet achieved full maturity in Nebraska.