Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression

Although depressed mood is a normal occurrence in response to adversity in all individuals, what distinguishes those who are vulnerable to major depressive disorder (MDD) is their inability to effectively regulate negative mood when it arises. Investigating the neural underpinnings of adaptive emotion regulation and the extent to which such processes are compromised in MDD may be helpful in understanding the pathophysiology of depression. We report results from a functional magnetic resonance imaging study demonstrating left-lateralized activation in the prefrontal cortex (PFC) when downregulating negative affect in nondepressed individuals, whereas depressed individuals showed bilateral PFC activation. Furthermore, during an effortful affective reappraisal task, nondepressed individuals showed an inverse relationship between activation in left ventrolateral PFC and the amygdala that is mediated by the ventromedial PFC (VMPFC). No such relationship was found for depressed individuals, who instead show a positive association between VMPFC and amygdala. Pupil dilation data suggest that those depressed patients who expend more effort to reappraise negative stimuli are characterized by accentuated activation in the amygdala, insula, and thalamus, whereas nondepressed individuals exhibit the opposite pattern. These findings indicate that a key feature underlying the pathophysiology of major depression is the counterproductive engagement of right prefrontal cortex and the lack of engagement of left lateral-ventromedial prefrontal circuitry important for the downregulation of amygdala responses to negative stimuli.

Inertia in Japanese organizations: knowledge management routines and failure to innovate

This paper argues that features of Japanese organizations, previously held to be the foundations of innovation, change and flexibility, can equally be significant barriers to change, innovation and adaptation in turbulent economic environments. This paper draws on two in-depth case studies of Japanese organizations. It shows how, in both cases, these firms displayed specific weaknesses in the ways in which they integrate and bundle knowledge, in particular around their research and development (R&D) functions. Despite the adoption of strategies of technological innovation and internationalization, the data suggest that the pursuit of both strategies is beset by barriers of inertia. Embedded internal network connections and knowledge-sharing routines between central R&D and other divisions are inappropriate for the revised strategy. Existing external connections, with preferred suppliers and customers within keiretsu structures, and close relationships with existing R&D partners retard these firms' strategic flexibility. With a limited variety of latent routines, knowledge, capabilities and agency to draw on when needed, these firms have limited organizational responsiveness and high levels of path-dependency.

Relationships between the plasma concentrations of insulin-like growth factor-I in dairy cows and their fertility and milk yield

The relationships between insulin-like growth factor-I (IGF-I) and the fertility and milk yield of Holstein-Friesian dairy cows were investigated. The concentration of IGF-I in blood was measured weekly from one week before to 12 weeks after calving in 177 multiparous cows and at four times during this period in 142 primiparous cows; the concentration of IGF-I in milk was measured in 50 of the multiparous cows. The plasma concentrations of IGF-I were higher in the primiparous than in the multiparous animals. in the primiparous cows, high concentrations of IGF-I before calving were associated with longer calving to conception intervals. Conversely, in the multiparous cows low concentrations of IGF-I before and after calving were associated with a failure to conceive, despite repeated services. Multiparous cows with IGF-I concentrations of greater than 25 ng/ml in the week after calving were 11 times more likely to conceive to first service than those with lower concentrations. Concentrations of IGF-I greater than 50 ng/ml at first service increased the likelihood of conception five-fold. Cows with higher peak milk yields had lower plasma concentrations of IGF-I and took longer to return to ovarian cyclicity. The negative relationship between milk yield and return to cyclicity was stronger in the multiparous cows (P<0(.)002) than in the primiparous cows (P<0(.)04). The concentrations of IGF-I in milk followed a different pattern and were not associated with the changes in plasma IGF-I or fertility.

Contribution of insect pollinators to crop yield and quality varies with agricultural intensification

Background: Up to 75% of crop species benefit at least to some degree from animal pollination for fruit or seed set and yield. However, basic information on the level of pollinator dependence and pollinator contribution to yield is lacking for many crops. Even less is known about how insect pollination affects crop quality. Given that habitat loss and agricultural intensification are known to decrease pollinator richness and abundance, there is a need to assess the consequences for different components of crop production. Methods: We used pollination exclusion on flowers or inflorescences on a whole plant basis to assess the contribution of insect pollination to crop yield and quality in four flowering crops (spring oilseed rape, field bean, strawberry, and buckwheat) located in four regions of Europe. For each crop, we recorded abundance and species richness of flower visiting insects in ten fields located along a gradient fromsimple to heterogeneous landscapes. Results: Insect pollination enhanced average crop yield between 18 and 71% depending on the crop. Yield quality was also enhanced in most crops. For instance, oilseed rape had higher oil and lower chlorophyll contents when adequately pollinated, the proportion of empty seeds decreased in buckwheat, and strawberries’ commercial grade improved; however, we did not find higher nitrogen content in open pollinated field beans. Complex landscapes had a higher overall species richness of wild pollinators across crops, but visitation rates were only higher in complex landscapes for some crops. On the contrary, the overall yield was consistently enhanced by higher visitation rates, but not by higher pollinator richness. Discussion. For the four crops in this study, there is clear benefit delivered by pollinators on yield quantity and/or quality, but it is not maximized under current agricultural intensification. Honeybees, the most abundant pollinator, might partially compensate the loss of wild pollinators in some areas, but our results suggest the need of landscape-scale actions to enhance wild pollinator populations.

A temporal limit to the association between flag leaf life extension by fungicides and wheat yields

Three field experiments, each repeated over two or three seasons, on winter wheat investigated a possible limit to the association between grain yield and flag leaf life, as extended by fungicide application. The experiments involved up to six cultivars and different application rates, timings and frequencies of the strobilurin azoxystrobin and the triazole epoxiconazole. In the 2000/01 and 2001/02 seasons, the relationships between the thermal time to 37 % green flag leaf area (m) and yield deviated from linearity. 'Broken stick' models were fitted to cultivar x experiment combinations within each season and the limit to the benefit to yield associated with extending flag leaf life was 700 degrees C days (S.E. = 20.7) and 725 degrees C days (S.E. = 9.33) after anthesis in 2000/01 and 2001/02, respectively. In 2002/03, the relationship between yield and in did not deviate significantly (P > 0.05) from linearity, but in this latter year the fungicide application failed to increase In past 700 degrees C days. (c) 2004 Elsevier B.V. All rights reserved.

Synthesis of enantiopure prolines via exo-stereoselective 1,3-dipolar cycloadditions to acetone-derived chiral stabilised azomethine ylides

The chiral stabilised azomethine ylide formed from condensation of the dimethyl acetal of acetone with (5S)-5-phenylmorpholinone undergoes stereoselective exo-cycloaddition reactions with a range of doubly and singly activated dipolarophiles when generated in the presence of excess (MgBr2OEt2)-O-.. The cycloadducts can be degraded to yield enantiomerically pure proline derivatives.

Separation of oligosaccharides from caprine milk whey, prior to prebiotic evaluation

Milk oligosaccharides are believed to have beneficial biological properties. Caprine milk has a relatively high concentration of oligosaccharides in comparison to other ruminant milks and has the closest oligosaccharide profile to human milk. The first stage in recovering oligosaccharides from caprine milk whey, a by-product of cheese making, was accomplished by ultrafiltration to remove proteins and fat globules, leaving more than 97% of the initial carbohydrates, mainly lactose, in the permeate. The ultrafiltered permeate was further processed using a 1 kDa ‘tight’ ultrafiltration membrane, which retained less than 7% of the remaining lactose. The final retentate was fractionated by preparative scale molecular size exclusion chromatography, to yield 28 fractions, of which oligosaccharide-rich fractions were detected somewhere between fractions 9/10 to 16/17, suitable for functionality and gut health promotion testing. All fractions were evaluated for their oligosaccharide and carbohydrate profiles using three complementary analytical methods.

Variability in fecal water genotoxicity, determined using the Comet assay, is independent of endogenous N-nitroso compound formation attributed to red meat consumption

Red meat consumption causes a dose-dependent increase in fecal apparent total N-nitroso compounds (ATNC). The genotoxic effects of these ATNCs were investigated using two different Comet assay protocols to determine the genotoxicity of fecal water samples. Fecal water samples were obtained from two studies of a total of 21 individuals fed diets containing different amounts of red meat, protein, heme, and iron. The first protocol incubated the samples with HT-29 cells for 5 min at 4 degrees C, whereas the second protocol used a longer exposure time of 30 min and a higher incubation temperature of 37 degrees C. DNA strand breaks were quantified by the tail moment (DNA in the comet tail multiplied by the comet tail length). The results of the two Comet assay protocols were significantly correlated (r = 0.35, P = 0.003), however, only the second protocol resulted in detectable levels of DNA damage. Inter-individual effects were variable and there was no effect on fecal water genotoxicity by diet (P > 0.20), mean transit time (P = 0.588), or weight (P = 0.705). However, there was a highly significant effect of age (P = 0.019). There was no significant correlation between concentrations of ATNCs in fecal homogenates and fecal water genotoxicity (r = 0.04, P = 0.74). ATNC levels were lower in fecal water samples (272 microg/kg) compared to that of fecal homogenate samples (895 microg/kg) (P < 0.0001). Failure to find dietary effects on fecal water genotoxicity may therefore be attributed to individual variability and low levels of ATNCs in fecal water samples.

Priority setting in healthcare: from arbitrariness to societal values

This paper develops an account of the normative basis of priority setting in health care as combining the values which a given society holds for the common good of its members, with the universal provided by a principle of common humanity. We discuss national differences in health basket in Europe and argue that health care decision-making in complex social and moral frameworks is best thought of as anchored in such a principle by drawing on the philosophy of need. We show that health care needs are ethically ‘thick’ needs whose psychological and social construction can best be understood in terms of David Wiggins's notion of vital need: a person's need is vital when failure to meet it leads to their harm and suffering. The moral dimension of priority setting which operates across different societies’ health care systems is located in the demands both of and on any society to avoid harm to its members.

Evidence for a climate signal in trends of global crop yield variability over the past 50 years

Low variability of crop production from year to year is desirable for many reasons, including reduced income risk and stability of supplies. Therefore, it is important to understand the nature of yield variability, whether it is changing through time, and how it varies between crops and regions. Previous studies have shown that national crop yield variability has changed in the past, with the direction and magnitude dependent on crop type and location. Whilst such studies acknowledge the importance of climate variability in determining yield variability, it has been assumed that its magnitude and its effect on crop production have not changed through time and, hence, that changes to yield variability have been due to non-climatic factors. We address this assumption by jointly examining yield and climate variability for three major crops (rice, wheat and maize) over the past 50 years. National yield time series and growing season temperature and precipitation were de-trended and related using multiple linear regression. Yield variability changed significantly in half of the crop–country combinations examined. For several crop–country combinations, changes in yield variability were related to changes in climate variability.

Whole-brain functional connectivity during emotional word classification in medication-free Major Depressive Disorder: abnormal salience circuitry and relations to positive emotionality

Major Depressive Disorder (MDD) has been associated with biased processing and abnormal regulation of negative and positive information, which may result from compromised coordinated activity of prefrontal and subcortical brain regions involved in evaluating emotional information. We tested whether patients with MDD show distributed changes in functional connectivity with a set of independently derived brain networks that have shown high correspondence with different task demands, including stimulus salience and emotional processing. We further explored if connectivity during emotional word processing related to the tendency to engage in positive or negative emotional states. In this study, 25 medication-free MDD patients without current or past comorbidity and matched controls (n=25) performed an emotional word-evaluation task during functional MRI. Using a dual regression approach, individual spatial connectivity maps representing each subject’s connectivity with each standard network were used to evaluate between-group differences and effects of positive and negative emotionality (extraversion and neuroticism, respectively, as measured with the NEO-FFI). Results showed decreased functional connectivity of the medial prefrontal cortex, ventrolateral prefrontal cortex, and ventral striatum with the fronto-opercular salience network in MDD patients compared to controls. In patients, abnormal connectivity was related to extraversion, but not neuroticism. These results confirm the hypothesis of a relative (para)limbic-cortical decoupling that may explain dysregulated affect in MDD. As connectivity of these regions with the salience network was related to extraversion, but not to general depression severity or negative emotionality, dysfunction of this network may be responsible for the failure to sustain engagement in rewarding behavior.

Automatic ability attribution after failure: a dual process view of achievement attribution

Causal attribution has been one of the most influential frameworks in the literature of achievement motivation, but previous studies considered achievement attribution as relatively deliberate and effortful processes. In the current study, we tested the hypothesis that people automatically attribute their achievement failure to their ability, but reduce the ability attribution in a controlled manner. To address this hypothesis, we measured participants’ causal attribution belief for their task failure either under the cognitive load (load condition) or with full attention (no-load condition). Across two studies, participants attributed task performance to their ability more in the load than in the no-load condition. The increased ability attribution under cognitive load further affected intrinsic motivation. These results indicate that cognitive resources available after feedback play crucial roles in determining causal attribution belief, as well as achievement motivations. (PsycINFO Database Record (c) 2013 APA, all rights reserved)(journal abstract)

A method for merging nadir-sounding climate records, with an application to the global-mean stratospheric temperature data sets from SSU and AMSU

A method is proposed for merging different nadir-sounding climate data records using measurements from high-resolution limb sounders to provide a transfer function between the different nadir measurements. The two nadir-sounding records need not be overlapping so long as the limb-sounding record bridges between them. The method is applied to global-mean stratospheric temperatures from the NOAA Climate Data Records based on the Stratospheric Sounding Unit (SSU) and the Advanced Microwave Sounding Unit-A (AMSU), extending the SSU record forward in time to yield a continuous data set from 1979 to present, and providing a simple framework for extending the SSU record into the future using AMSU. SSU and AMSU are bridged using temperature measurements from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS), which is of high enough vertical resolution to accurately represent the weighting functions of both SSU and AMSU. For this application, a purely statistical approach is not viable since the different nadir channels are not sufficiently linearly independent, statistically speaking. The near-global-mean linear temperature trends for extended SSU for 1980–2012 are −0.63 ± 0.13, −0.71 ± 0.15 and −0.80 ± 0.17 K decade−1 (95 % confidence) for channels 1, 2 and 3, respectively. The extended SSU temperature changes are in good agreement with those from the Microwave Limb Sounder (MLS) on the Aura satellite, with both exhibiting a cooling trend of ~ 0.6 ± 0.3 K decade−1 in the upper stratosphere from 2004 to 2012. The extended SSU record is found to be in agreement with high-top coupled atmosphere–ocean models over the 1980–2012 period, including the continued cooling over the first decade of the 21st century.

Learning to lead for business growth – implications for supporting SMEs in Wales

The Welsh private and third sectors are heavily dependent on SMEs. Consequently the performance of SMEs is critical to the performance of the Welsh economy. Substantial public funds, particularly from European Structural Funds, have been allocated to support these since 2000. The majority of programmes thus funded have been led from within the Welsh Government. This paper reports interim evaluation findings from one intervention led by two Welsh higher education institutions (HEIs), namely the LEAD Wales programme. The programme is an extended intervention to support the leadership skills of owner-managers and incorporates a range of learning methods, including formal masterclasses, but emphasizes situated and experiential learning through action learning, coaching and peer-to-peer exchange exercises. The programme’s impact is assessed on the experiences of 325 participants, of whom 217 have completed the programme. The paper concludes that situated learning methods, through which participants are able to draw from shared history and experience over an extended period are critical to programme success. By contrast, short-term thematic teaching, based around more formal, hierarchical learning is less likely to yield significant and sustainable economic benefits. The implications of this for business support in Wales are discussed.