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5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats
No full textThough obesity is a global epidemic, the physiological mechanisms involved are little understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesized that maternal diet influences fetal 5-HT exposure, which then influences central appetite network development and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant low protein fed rat mothers exhibited elevated serum 5-HT, which was also evident in the placenta and fetal brains at E16.5. This increase was associated with a reduced hypothalamic expression of the primary 5-HT receptor influencing appetite, 5-HT2CR in the fetal brain as well as neonatal and adult hypothalamus. As expected, reduced 5-HT2CR expression was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite via 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We reveal that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC and that 5-HT2AR mRNA is increased in the hypothalamus of in utero growth restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3-months of age are more sensitive to 5-HT2AR agonist-induced appetite suppression. These findings may not only reveal a 5-HT-mediated mechanism underlying programming of obesity susceptibility but also provide a promising means to correct it, via a 5-HT2AR agonist treatment
The decisional balance: an interpretative phenomenological analysis reflecting the transition from pain management services to chronic pain support group attendance
No full textOBJECTIVES:
Transitioning from clinical care to community-based self-management represents a significant challenge, throughout which social support can facilitate health adjustment and quality of life. However, community-centred, peer-led support structures are often underused. This study aimed to investigate the decision-making processes involved in the choice to attend a chronic pain support group (CPSG) following discharge from a Pain Management Programme.
DESIGN:
An in-depth, qualitative analysis was undertaken using interpretative phenomenological analysis, exploring participants' subjective experiences, decision-making, and rationale for initial CPSG attendance.
METHODS:
Twelve participants (four males, eight females) were recruited from a regional CPSG and completed semi-structured interviews lasting between 45 and 120 min. Interviews were transcribed verbatim and analysed idiographically before a cross-case analysis was completed.
RESULTS:
Analysis of transcripts resulted in three superordinate themes: (1) The thirst for comparative friendship; (2) conjecture and the imminent choice; (3) progressive pain management. These themes reflect a desire for empathic, socially comparative friendships and the search for a forum in which to enhance pain self-management strategies, yet also internal conflict over initial CPSG attendance.
CONCLUSION:
Social support and associated friendships are attractive to prospective CPSG members and are conceptualized as opportunities to engage in social comparison and nurture self-care. The first visit to the support group presents a significant hurdle, but can be facilitated by managing the transition between therapeutic care and CPSG attendance. Clinicians can challenge preconceptions, foster positive viewpoints regarding the group and support collective decision-making to attend. Following initial attendance, psychosocial well-being was enhanced. Statement of contribution What is already known on this subject? Social support functions as a protective buffer against declining health. Joining a peer-led support group can be initially intimidating and the first visit presents a significant hurdle. What does this study add? Participants are predominantly attracted to support groups due to the opportunity to develop new friendships. Health-related peer groups function as fora for social comparison, enhancing self-esteem and self-efficacy. Experience of pain management programmes primes willingness to attend support groups. The initial decision to attend is difficult but facilitated by collective, group decision-making processes. Health care professionals dynamically prime the transition towards peer support structures
IL-1β (interleukin-1β) stimulates the production and release of multiple cytokines and chemokines by human preadipocytes
Get PDFThe effect of IL-1β on cytokine and chemokine production by human preadipocytes has been examined. Preadipocytes were incubated with IL-1β and cytokine and chemokine release measured at 24 h by protein arrays, while the expression of cytokine/chemokine genes was assessed by qPCR at 4 and 24 h. IL-1β stimulated the secretion of multiple cytokines/chemokines, including IL-6, IL-8, IL-10, IL-13, MCP-4, TNFα and IP-10. IL-10 was not released by un-stimulated preadipocytes, while IL-6 exhibited the greatest response to IL-1β (453-fold increase). IL-16 and IL-12p40 did not respond to IL-1β. qPCR demonstrated that IL-1β markedly stimulated CCL3, CSF3 and CXCL10expression at 4 h (>900-fold mRNA increase). A time-course indicated that while CCL13 (encoding MCP-4) exhibited minimal basal expression in preadipocytes, expression increased progressively following differentiation. Human preadipocytes are highly sensitive to IL-1β, the cytokine stimulating a major inflammatory response in these cells similar to that in mature adipocytes
A Grounded Theory Analysis of a Focus Group Study
Get PDFDecisions about whether to reassess the clinical condition of patients in a minimally conscious state are a cornerstone of clinical care and management. The outcome of clinical reassessment determines whether efforts to rehabilitate should be escalated, maintained, or targeted more specifically to achieve optimal outcomes. The results of reassessment also underpin decisions to withhold or withdraw life-sustaining treatment from this patient group.
Actual decisions about whether to reassess tend to be taken by members of multidisciplinary teams. For this reason, focus groups were chosen to ascertain the views and perceptions of senior decision-makers as to whether minimally conscious patients should have a fundamental “right” to be reassessed. Constructivist grounded theory was used to analyze the data. The results reveal that a range of factors will influence whether these patients are reassessed clinically.
This case study discusses why focus groups using a grounded theory analysis were chosen to address the research question. A description is provided of the coding process that was used to develop theory from the focus group data. This case study will help researchers to understand how these methodologies are carried out as well as to identify the types of insight that can be gained from their use
Passing the time when in pain: investigating the role of musical valence
No full textThe effective management of pain outside of clinical settings represents a significant challenge to health services. Music listening has been successfully used as a method of pain management, with the greatest benefits to listeners evident if the music is familiar, preferred and has emotional resonance. This study examined the role of self-selected emotion-inducing music used for pain management (pain tolerance, intensity, perceived control, distraction and anxiety reduction) during the cold pressor test. In a repeated-measures design, four cold pressor tests were used to induce short-term, acute pain, whilst 41 participants listened either to happy, sad, relaxing or no music. Findings indicated that music enhanced pain tolerance over no music, and happy and relaxing music increased pain tolerance and altered time perception to a greater extent than sad music. Happy and relaxing music facilitated distraction from pain and enhanced perceived pain control. Relaxing music additionally had anxiolytic properties and reduced pain intensity. Results suggest that music’s inclusion in pain management is justified and that music with happy and relaxing components can be used to facilitate coping with pain in a non-clinical context
Enhanced receiver architectures for processing multi GNSS signals in a single chain : based on partial differential equations mathematical model
No full textThe focus of our research is on designing a new architecture (RF front-end and digital) for processing multi GNSS signals in a single receiver chain. The motivation is to save in overhead cost (size, processing time and power consumption) of implementing multiple signal receivers side-by-side on-board Smartphones.
This thesis documents the new multi-signal receiver architecture that we have designed. Based on this architecture, we have achieved/published eight novel contributions. Six of these implementations focus on multi GNSS signal receivers, and the last two are for multiplexing Bluetooth and GPS received signals in a single processing chain. We believe our work in terms of the new innovative and novel techniques achieved is a major contribution to the commercial world especially that of Smartphones. Savings in both silicon size and processing time will be highly beneficial to reduction of costs but more importantly for conserving the energy of the battery. We are proud that we have made this significant contribution to both industry and the scientific research and development arena.
The first part of the work focus on the Two GNSS signal detection front-end approaches that were designed to explore the availability of the L1 band of GPS, Galileo and GLONASS at an early stage. This is so that the receiver devotes appropriate resources to acquire them. The first approach was based on folding the carrier frequency of all the three GNSS signals with their harmonics to the First Nyquist Zone (FNZ), as depicted by the BandPass Sampling Receiver technique (BPSR). Consequently, there is a unique power distribution of these folded signals based on the actual present signals that can be detected to alert the digital processing parts to acquire it. Volterra Series model is used to estimate the existing power in the FNZ by extracting the kernels of these folded GNSS signals, if available. The second approach filters out the right-side lobe of the GLONASS signal and the left-side lobe of the Galileo signal, prior to the folding process in our BPSR implementation. This filtering is important to enable none overlapped folding of these two signals with the GPS signal in the FNZ. The simulation results show that adopting these two approaches can save much valuable acquisition processing time.
Our Orthogonal BandPass Sampling Receiver and Orthogonal Complex BandPass Sampling Receiver are two methods designed to capture any two wireless signals simultaneously and use a single channel in the digital domain to process them, including tracking and decoding, concurrently. The novelty of the two receivers is centred on the Orthogonal Integrated Function (OIF) that continuously harmonies the two received signals to form a single orthogonal signal allowing the “tracking and decoding” to be carried out by a single digital channel. These receivers employ a Hilbert Transform for shifting one of the input signals by 90-degrees. Then, the BPSR technique is used to fold back the two received signals to the same reference frequency in the FNZ. Results show that these designed methods also reduce the sampling frequency to a rate proportional to the maximum bandwidth, instead of the summation of bandwidths, of the input signals.
Two combined GPS L1CA and L2C signal acquisition channels are designed based on applying the idea of the OIF to enhance the power consumption and the implementation complexity in the existing combination methods and also to enhance the acquisition sensitivity. This is achieved by removing the Doppler frequency of the two signals; our methods add the in-phase component of the L2C signal together with the in-phase component of the L1CA signal, which is then shifted by 90-degree before adding it to the remaining components of these two signals, resulting in an orthogonal form of the combined signals. This orthogonal signal is then fed to our developed version of the parallel-code-phase-search engine. Our simulation results illustrate that the acquisition sensitivity of these signals is improved successfully by 5.0 dB, which is necessary for acquiring weak signals in harsh environments.
The last part of this work focuses on the tracking stage when specifically multiplexing Bluetooth and L1CA GPS signals in a single channel based on using the concept of the OIF, where the tracking channel can be shared between the two signals without losing the lock or degrading its performance. Two approaches are designed for integrating the two signals based on the mathematical analysis of the main function of the tracking channel, which the Phase-Locked Loop (PLL). A mathematical model of a set of differential equations has been developed to evaluate the PLL when it used to track and demodulated two signals simultaneously. The simulation results proved that the implementation of our approaches has reduced by almost half the size and processing time
Keynes and Wall Street
Get PDFThis article examines in detail how John Maynard Keynes approached investing in the US stock market on behalf of his Cambridge College after the 1929 Crash. We exploit the considerable archival material documenting his portfolio holdings, his correspondence with investment advisors and his two visits to the US in the 1930s. Whilst he followed his enthusiasm for common stocks, he was equally attracted to investing in preferred stocks. His US stock picks reflected his detailed analysis of company fundamentals and a pronounced value approach. Already in this period, therefore, it is possible to see the origins of some of the investment techniques adopted by professional investors in the latter half of the twentieth century
Analysing Fish Behaviours Using Three-Dimensional Qualitative Trajectory Calculus 2016
Get PDFFish swim freely in water and their 3D spatial interactions
may carry important information for biological study. The two-dimensional Qualitative Trajectory Calculus (QTC2D), a spatiotemporal calculus, is a method for representing and reasoning about movements of objects in a qualitative framework. This emerging technique encodes the spatial geometric relationships between distinct objects, such as machines, humans or animals. This paper presents a method for generalising QTC2D into 3D space, called 3DQTC, as a work-in-progress. The 3DQTC method is based on a geometrical analysis method of estimating the 3D orientation
of �fish. Initial results indicate the potential of representing and analysing the �fish behaviours in 3D space. 3DQTC is also demonstrated as a means
of extracting useful information (e.g. follow and non-follow behaviours)which cannot be achieved by QTC2D. We conclude by discussing further work and development
Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity
No full textThe free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationship studies of a previously disclosed nonacidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although a significant fraction of these noncarboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice resulted in significantly increased insulin sensitivity and a moderate but significant reduction in bodyweight, effects that were also present in mice lacking FFA1 but absent in mice lacking FFA4