bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstruction of climate and vegetation changes of Lake Bayanchagan (Inner Mongolia): Holocene variability of the East Asian monsoon
Authors: Jiang Wenying , Guo Zhengtang , Sun Xiangjun , Wu Haibin , Chu Guoqiang , Yuan Baoyin , Hatté Chritine , Guiot Jöel 
Published: February 2006

AbstractA high-resolution pollen and Pediastrum record, spanning 12,500 yr, is presented for Lake Bayanchagan , southern Inner Mongolia. Individual pollen taxa (PT-MAT) and the PFT affinity scores (PFT-MAT) were used for quantitative climatic reconstruction from pollen and algal data. Both techniques indicate that a cold and dry climate, similar to that of today, prevailed before 10,500 cal yr B.P. The wettest climate occurred between ∼10,500 and 6500 cal yr B.P., at which time annual precipitation was up to 30–60% higher than today. The early Holocene increases in temperature and precipitation occurred simultaneously, but mid-Holocene cooling started at approximately 8000 cal yr B.P., 1500 yr earlier than the drying. Vegetation reconstruction was based on the objective assignment of pollen taxa to the plant functional type. The results suggest that this region was dominated by steppe vegetation throughout the Holocene, except for the period ∼9200 to ∼6700 cal yr B.P., when forest patches were relatively common. Inner Mongolia is situated at the limit of the present East Asian monsoon and patterns of vegetation and climate changes in that region during the Holocene probably reflect fluctuations in the monsoon's response to solar insolation variations. The early to middle Holocene monsoon undoubtedly extended to more northern latitudes than at present.
Asset allocation in Finnish pension funds
Authors: ALESTALO NOORA , PUTTONEN VESA 
Published: February 2006

This paper empirically examines the strategic asset allocation and the asset/liability issues in the Finnish defined benefit pension funds. The results indicate that there is a relationship between the liability structure and the asset allocation. While pension funds with younger participants have more equity exposure, more mature pension funds have more fixed income investments.Wide dispersion in asset allocations is also found between the funds. One fund holds its entire portfolio in fixed income securities, whereas other funds have none or only few fixed income holdings. Equity investments also vary dramatically, ranging from 0% to over 70% of the asset allocation. The same applies to investments in a sponsor, real estate investment, and money market investments. A portion of these different asset allocations is explained by the liability structure, but another part remains unexplained. The other variables affecting strategic asset allocation of a pension fund are not obvious, but they could include factors such as regulatory environment, historical reasons, mean-variance optimization instead of ALM, sponsor's own preferences or pension fund's irrationality. Analyzing these factors would be a fruitful topic for further research. Additionally, international comparisons would be a fruitful topic for further investigation.
The role of central 5‐hydroxytryptamine (5‐HT, serotonin) receptors in the control of micturition
Authors: Ramage Andrew G. 
Published: February 2006

At present the most investigated 5‐HT receptor that has been shown to play a role in the control of micturition is the 5‐HT1Areceptor followed by 5‐HT7, 5‐HT2and 5‐HT3receptors. Most experiments focus on the control these receptors have on the parasympathetic outflow to the bladder and the somatic outflow to the external urethral sphincter (EUS) in the rat. Furthermore, 5‐HT1Aand 5‐HT7receptors have been identified as having an excitatory physiological role in the control of bladder function. 5‐HT1Areceptors act, at least in the rat, at both a spinal (probably a heteroreceptor) and supraspinal (probably an autoreceptor) level, while 5‐HT7receptors only act at a supraspinal level. Additionally, in the rat, 5‐HT administered at a spinal or supraspinal site has an excitatory action, although earlier experiments have shown that activating 5‐HT‐containing brain areas causes inhibition of the bladder. Recent experiments have also indicated that blockade of the 5‐HT1Areceptor pathway shows rapid tolerance. However, no data exist for the development of tolerance for the 5‐HT7receptor pathway. Neither receptor seems to play a role in the control of the urethra. Regarding 5‐HT2receptors, activation of this receptor subtype inhibits micturition, and this inhibitory action may occur at a spinal, supraspinal or both levels. Although no physiological role for 5‐HT2Creceptors can yet be identified, 5‐HT2Creceptors have been implicated in the proposed supraspinal tonically active 5‐HT1Aautoreceptor (negative feedback) pathway. This proposition reconciles the data that central 5‐HT‐containing pathways are inhibitory to micturition, while 5‐HT1Areceptors, although inhibitory to adenylyl cyclase, have an excitatory function. This is because activation of 5‐HT1Aautoreceptors reduces the release of 5‐HT thus reducing the activation of the 5‐HT2Creceptors, which are inhibitory in the control of micturition (disinhibition). Furthermore, 5‐HT2Areceptors in the rat and 5‐HT2Creceptors in the guinea pig cause activation of the EUS. In this respect, 5‐ht5Areceptors have also been identified in Onuf's nucleus, the site of somatic motoneurones controlling this sphincter. In the cat there is very little evidence to indicate that 5‐HT receptors are involved in micturition except under pathological conditions in which activation of 5‐HT1Areceptors causes inhibition of micturition. Interestingly, under such conditions 5‐HT1Areceptors cause excitation of the EUS. Nevertheless, spinal 5HT3receptors have been implicated in the physiological control of micturition in the cat, but not yet in the rat. Overall, the data support the view that 5‐HT receptors are important in the control of micturition. However, many more studies are required to fully understand these roles and why there are such species differences.British Journal of Pharmacology(2006)147, S120–S131. doi:10.1038/sj.bjp.0706504
In vitromodels: research in physiology and pharmacology of the lower urinary tract
Authors: Moreland Robert B. 
Published: February 2006

The physiology and pharmacology of the lower urinary tract has advanced based, in part, due to thein vitroassays that have facilitated this exploration. Such assays have led to the development of novel and selective molecules that have been used to characterize different receptor and enzyme systems in the larger context ofin vivopharmacology. These assays can be classified by sites of action of drugs into the following categories: receptors, effector enzymes and enzymes that terminate the responses. In this review, representative assays are presented based on our experience in male erectile dysfunction.British Journal of Pharmacology(2006)147, S56–S61. doi:10.1038/sj.bjp.0706505
Muscarinic receptors in the bladder: from basic research to therapeutics
Authors: Hegde Sharath S. 
Published: February 2006

Muscarinic receptor antagonists (antimuscarinics) serve as the cornerstone in the pharmacological management of overactive bladder (OAB) by relieving the symptoms of urgency, frequency and incontinence. These drugs operate primarily by antagonizing post‐junctional excitatory muscarinic receptors (M2/M3) in the detrusor. The combination of pharmacological and gene knockout studies has greatly advanced our understanding of the functional role of muscarinic receptors in the bladder. M3receptors produce direct smooth muscle contraction by a mechanism that relies on entry of extracellular calcium through L‐type channels and activation of a rho kinase. M2receptors, which predominate in number, appear to facilitate M3‐mediated contractions. M2receptors can also produce bladder contractions indirectly by reversing cAMP‐dependent β‐adrenoceptor‐mediated relaxation, although the physiological role of β‐adrenoceptors in detrusor relaxation is controversial. Emerging evidence suggests that muscarinic receptors in the urothelium/suburothelium can modulate the release of certain factors, which in turn may affect bladder function at the efferent or afferent axis. Currently, oxybutynin, tolterodine, darifenacin, solifenacin and trospium are the five major antimuscarinics approved for the treatment of OAB. Comparative clinical studies have shown that oxybutynin and solifenacin may be marginally more effective than tolterodine, although the latter seems to be better tolerated. Pharmacokinetic–pharmacodynamic analyses using plasma concentrations of ‘total drug’ indicate that, at therapeutic doses, the clinical efficacy of darifenacin and solifenacin may be driven primarily by selective M3receptor occupation, whereas the pharmacodynamic effects of pan‐selective molecules (such as tolterodine, trospium) may potentially involve multiple receptors, including M2and M3. Furthermore, high M3receptor occupation is the likely explanation for the greater propensity of darifenacin and oxybutynin to cause dry mouth and/or constipation. Although the recently introduced drugs represent a significant improvement over older drugs, especially with respect to the convenience of dosing schedule, their overall efficacy and tolerability profile is still less than optimal and patient persistence with therapy is low. Recent advances in basic research have not yet offered a clear discovery path for improving the therapeutic index of antimuscarinic molecules. There is still an unmet need for an antimuscarinic medicine with superior clinical effectiveness that can translate into better persistence on therapy.British Journal of Pharmacology(2006)147, S80–S87. doi:10.1038/sj.bjp.0706560
Integrative control of the lower urinary tract: preclinical perspective
Authors: de Groat William C. 
Published: February 2006

Storage and periodic expulsion of urine is regulated by a neural control system in the brain and spinal cord that coordinates the reciprocal activity of two functional units in the lower urinary tract (LUT): (a) a reservoir (the urinary bladder) and (b) an outlet (bladder neck, urethra and striated muscles of the urethral sphincter). Control of the bladder and urethral outlet is dependent on three sets of peripheral nerves: parasympathetic, sympathetic and somatic nerves that contain afferent as well as efferent pathways. Afferent neurons innervating the bladder have A‐δ or C‐fibre axons. Urine storage reflexes are organized in the spinal cord, whereas voiding reflexes are mediated by a spinobulbospinal pathway passing through a coordination centre (the pontine micturition centre) located in the brainstem. Storage and voiding reflexes are activated by mechanosensitive A‐δ afferents that respond to bladder distension. Many neurotransmitters including acetylcholine, norepinephrine, dopamine, serotonin, excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide and neuropeptides are involved in the neural control of the LUT. Injuries or diseases of the nervous system as well as disorders of the peripheral organs can produce LUT dysfunctions including: (1) urinary frequency, urgency and incontinence or (2) inefficient voiding and urinary retention. Neurogenic detrusor overactivity is triggered by C‐fibre bladder afferent axons, many of which terminate in the close proximity to the urothelium. The urothelial cells exhibit ‘neuron‐like’ properties that allow them to respond to mechanical and chemical stimuli and to release transmitters that can modulate the activity of afferent nerves.British Journal of Pharmacology(2006)147, S25–S40. doi:10.1038/sj.bjp.0706604
Lower urinary tract disease: what are we trying to treat and in whom?
Authors: Heaton Jeremy P W. 
Published: February 2006

The diseases of the lower urinary tract are traditionally divided into abnormalities of storage and abnormalities of emptying. The targets for therapy were the organs most responsible for influencing storage and emptying. Modern understanding places the symptomatic status of the patient as the overriding criterion for treatment. It also accommodates a broader understanding of multiple and overlapping systems. Symptoms of voiding dysfunction have been clearly shown to be associated with symptoms of other genitourinary disease, for example, erectile dysfunction (ED). Treatment of voiding dysfunction has also been shown to have effects (adverse or beneficial) in these other domains. Thus, the symptoms of lower urinary tract disease (LUTD) that have to be considered now as targets relevant to these therapies include ED, ejaculatory dysfunction, sexual desire, sexual pain disorders and female sexual dysfunction. The anatomic, neural and endocrine systems that support these symptomatic functions and dysfunctions span the range from the urogenital smooth muscle to the hypothalamus, the bladder sensory output to the micturition centre and growth factors to androgens. Potentially important targets also include vascular and spinal structures, sex hormones and nitric oxide as well as the obvious genes, enzymes and receptors. The epidemiological studies prove the convergence of LUTD when viewed through the lens of the current patient‐related outcomes and problem constructs. This convergence serves as a clear guidance to include wide ranging outcome instruments in all future studies with compounds being investigated for the treatment of LUTD. Out of these will come evidence of expected and unexpected collateral effects. The convergence should open the possibility to a different business model for developing therapeutic concepts. The blockbuster drug for a monolithic indication may be supplemented by agents with single or multiple pathway activity with smaller parallel targets. Using an approach based on patient reported outcomes to therapeutic targets not only widens the range of conditions, but also the patient types who can be considered as having LUTD.British Journal of Pharmacology (2006) 147, S2–S13. doi:10.1038/sj.bjp.0706620
Integrated control of lower urinary tract – clinical perspective
Authors: Fowler Clare J. 
Published: February 2006

The neural mechanisms that determine social bladder control are reviewed, with a particular emphasis on the role played by sensation in the process. Much has been learnt about the neural control of the bladder from studying patients with neurological disease and those disorders that are known to disrupt bladder storage are described. Possible approaches to treatment of the resulting incontinence are reviewed and it is acknowledged that in the future, the optimal treatment for incontinence may be determined by its precise underlying pathophysiology in each instance, for example, suprapontine causes requiring different medication to spinal causes. Although the main emphasis of urological research and development so far has been the treatment of incontinence, effective therapy for other bladder disorders such an impaired emptying or bladder pain could have an important impact on the bladder symptoms of many patients.British Journal of Pharmacology (2006) 147, S14–S24. doi:10.1038/sj.bjp.0706629
Animal models in urological disease and sexual dysfunction
Authors: McMurray Gordon , Casey James H. , Naylor Alasdair M. 
Published: February 2006

There are several conditions associated with dysfunction of the lower urinary tract or which result in a reduction in the ability to engage in satisfactory sexual function and result in significant bother to sufferers, partners and/or carers. This review describes some of the animal models that may be used to discover safe and effective medicines with which to treat them. While alpha adrenoceptor antagonists and 5‐alpha‐reductase inhibitors deliver improvement in symptom relief in benign prostatic hyperplasia sufferers, the availability of efficacious and well‐tolerated medicines to treat incontinence is less well served. Stress urinary incontinence (SUI) has no approved medical therapy in the United States and overactive bladder (OAB) therapy is limited to treatment with muscarinic antagonists (anti‐muscarinics). SUI and OAB are characterised by high prevalence, a growing ageing population and a strong desire from sufferers and physicians for more effective treatment options. High patient numbers with low presentation rates characterizes sexual dysfunction in men and women. The introduction of Viagra™ in 1998 for treating male erectile dysfunction and the success of the phosphodiesterase type 5 inhibitor class (PDE5 inhibitor) have indicated the willingness of sufferers to seek treatment when an effective alternative to injections and devices is available. The main value of preclinical models in discovering new medicines is to predict clinical outcomes. This translation can be established relatively easily in areas of medicine where there are a large number of drugs with different underlying pharmacological mechanisms in clinical usage. However, apart from, for example, the use of PDE5 inhibitors to treat male erectile dysfunction and the use of anti‐muscarinics to treat OAB, this clinical information is limited. Therefore, current confidence in existing preclinical models is based on our understanding of the biochemical, physiological, pathophysiological and psychological mechanisms underlying the conditions in humans and how they are reflected in preclinical models. Confidence in both the models used and the pharmacological data generated is reinforced if different models of related aspects of the same disorder generate confirmatory data. However, these models will only be fully validated in retrospect once the pharmacological agents they have helped identify are tested in humans.British Journal of Pharmacology(2006)147, S62–S79. doi:10.1038/sj.bjp.0706630
Growth factor signalling in prostatic growth: significance in tumour development and therapeutic targeting
Authors: Reynolds Arich Ryan , Kyprianou Natasha 
Published: February 2006

The intricate balance maintained between cell growth and proliferation factors and apoptosis‐inducing factors is fundamental to the regulation of prostate growth. Disruptions in this homeostasis often trigger the loss of apoptosis and the over‐expression of factors promoting cell survival and proliferation, inevitably leading to tumorigenesis and cancer. Deregulation of prostate growth during prostate cancer development and progression is characterized by apoptotic evasion, uncontrolled proliferation, and increased invasive potential. Thus, in advanced stages of disease progression, surviving prostate tumour cells acquire the ability to migrate and invade heterotopic tissues, with the bone and lymph nodes being the most common sites for human prostate cancer metastasis. The challenges in the implementation of effective therapeutic strategies for the treatment of advanced metastatic prostate cancer reflect the multidimensional nature and functional significance of antiapoptotic pathways in the emergence of therapeutic resistance of prostate tumours. In this chapter, we discuss the current understanding of the molecular mechanisms governing growth factor signalling pathways with often overlapping functions that contribute to loss of apoptosis control and activation of cell proliferation towards aggressive prostate tumorigenic growth and metastatic behaviour. While a full understanding of the prosurvival characteristics of these growth factor pathways is still evolving, the impact that growth factors such a epidermal growth factor and transforming growth factor‐β can be recognized by the vigorous attempts at therapeutic targeting of their key signalling steps.British Journal of Pharmacology (2006) 147, S144–S152. doi:10.1038/sj.bjp.0706635
Late‐stage clinical development in lower urogenital targets: sexual dysfunction
Authors: Azam Usman 
Published: February 2006

In recent years, late‐stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic, pre‐neoplasitic, and non‐neoplastic), and improvement in lower urinary tract symptoms. Despite the regulatory approval of compounds to treat erectile dysfunction (ED), benign prostatic hyperplasia, a number of treatments for overactive bladder, and stress urinary incontinence, there remains a deficiency in addressing a number of conditions that arise out of pathophysiological dysfunction resulting in lower urogenital tract sexual conditions. In terms of late‐stage clinical development, significant progress has most recently been made in MSD development, especially in understanding further a common and complex sexual dysfunction – that of premature ejaculation. The search also continues for compounds that improve ED in terms of better efficacy and superior safety profile compared to the currently marketed phosphodiesterase‐5‐inhibitors. Whilst there are no approved medications to treat the subtypes of FSD, there has been significant progress in attempting to better understand how to appropriately assess treatment benefit in clinical trial settings for this difficult to diagnose and treat condition. This review will focus on late‐stage human clinical development pertaining to MSD and FSD.British Journal of Pharmacology (2006) 147, S153–S159. doi:10.1038/sj.bjp.0706638
Nurses and Occupational Exposures to Bloodborne Viruses in Poland
Authors: Gańczak Maria , Milona Marta , Szych Zbigniew 
Published: February 2006

Study Objective.To record descriptions of occupational exposures to blood, determine factors predictive of exposure, and identify interventions that might reduce the frequency of exposure.Design.An analytic, cross-sectional survey.Study Population.A total of 601 nurses from surgical wards, operating rooms, and emergency departments.Study Instrument.An anonymous questionnaire developed by the authors on the basis of previously published guidelines was distributed between January and March 2003.Sampling.Random, with 18 hospitals selected from 2 urban and rural locations.Results.Almost half of respondents reported having had at least 1 puncture injury during the preceding year, 1 in 5 had exposure via mucous membranes, and more than half had worked at least once with a recent abrasion or cut on their hands. The number of injuries was independent of age (P = .26), duration of practice (P = .21), and workplace setting (P = .78). The percentage of nurses without percutaneous exposure during the preceding year was significantly higher in the group that received special HIV/AIDS training than in the group that did not (95% confidence interval, 5.8-24.1%; P<.002). The most recent exposure was primarily caused by hollow-bore needles, involved the palm and fingers II-V, was self-inflicted, took place during an elective procedure, and was not reported to the hospital's infection control center by 74% of respondents. The most common reason for not reporting the exposure (38% of cases) was the conviction that the source patient was not infected.Conclusions.Because of the large number of occupational exposures to blood, especially those due to injuries with hollow-bore needles, nurses should adopt more adequate behavioral strategies to prevent the transmission of blood-borne pathogens. Policies for providing adequate education programs tailored to encourage nurses to report all exposures are urgently required.