However, the number of participants with an eGFR of < 60 ml/min/1.73 m2 in our study was quite small; thus, these results should be interpreted carefully. Further investigations are needed to determine what level

of GFR deterioration begins to affect blood pressure. The potential limitations of our study include the single measurement of eGFR and selleck chemicals llc the use of dipstick proteinuria as a measure of kidney damage. Although the use of the urinary albumin-to-creatinine ratio (UACR) is preferable, as recommended in clinical guidelines, the presence of dipstick proteinuria has been shown to predict the future risk of albuminuria and is considered useful for screening (Matsushita et al., 2010). Also, we do not have data on causes of proteinuria or kidney dysfunction, although the recent CKD guidelines emphasize the importance of causes (KDIGO guideline, 2013). Other potential limitations of this study include the following: our study population consisted of a single

race and males only. With a healthy study population, the study might be underpowered to detect an association between reduced eGFR (< 60 ml/min/1.73 m2) and incident hypertension. Additionally, as with any observational study, we cannot rule out the possibility of residual unmeasured and unknown confounding factors. Both proteinuria, as assessed using a dipstick strip, and a reduced eGFR (< 50 ml/min/1.73 m2) are associated with incident hypertension independently of each other and known potential confounders. These findings suggest that both kidney damage and kidney dysfunction play important roles in the development of hypertension in young to middle-aged Japanese males. The authors MK-2206 cell line declare that there are no conflicts of interest. The authors thank the health care providers for their hard work and excellent assistance Tolmetin with this study. “
“Over 40% of cancers in the UK are attributable to lifestyle and environmental risk factors (Parkin et al., 2011). A large proportion of adults in England do not meet recommendations for key behaviours that influence

cancer risk, including alcohol consumption, diet, smoking and physical activity, and this is particularly apparent among disadvantaged groups (Craig and Mindell, 2012, Hamer et al., 2012, Stringhini et al., 2011 and West and Brown, 2012). Lower socioeconomic status groups also demonstrate more fatalistic attitudes towards cancer which could prevent timely help-seeking (Beeken et al., 2011). Various avenues have been used to inform the public about cancer prevention and the importance of early diagnosis. However, Modulators traditional channels such as printed information disproportionately reach those with higher literacy levels who tend to be from more affluent backgrounds (Berkman et al., 2011 and Boxell et al., 2012). This health literacy discrepancy compounds existing inequalities in access to and the understanding of cancer control information (Viswanath, 2005).

Recently, the concept of “innate memory” has been proposed [4] and [5] and has also inspired the design of vaccination approaches

focused on the stimulation of innate immunity. Several fish vaccines against viral or bacterial diseases, most of which comprise inactivated pathogens are now available UMI-77 datasheet [6]. However, researchers are Libraries working intensively to enhance vaccine efficiency by developing new vaccines, containing adjuvants and immunostimulants [7], and new formulations based on encapsulation [8], [9], [10], [11] and [12]. Encapsulating vaccines makes them more stable to the environment and to low pH and/or enzymatic reactions inside the treated organism [12] and [13]. Among the various encapsulation systems available, liposomes are especially attractive, as they are biocompatible and highly tuneable [14]; can actually enhance the efficacy of the vaccine, as has been reported in fish [15] and [16]; and can be used as labels to enable in vitro or in vivo tracking of the vaccine. Another factor

that researchers are endeavouring to improve in fish vaccines is administration, which is typically done by injection in adults. Research efforts are focused on creating non-stressful, easy to manage and low-cost vaccination Ku-0059436 price protocols to improve large-scale procedures based on immersion rather than on injection [6] and [17]. Our group recently developed nanoliposomes (called NLcliposomes) for simultaneous wide-spectrum anti-bacterial and anti-viral protection of farm-raised fish. First, we co-encapsulate two general immunostimulants: bacterial lipopolysaccharide (LPS) and poly(I:C), a synthetic analogue of dsRNA viruses. Then, we demonstrated that the NLc liposomes

Ketanserin were taken up in vitro by macrophages and that they regulated the expression of immunologically relevant genes (likely, by triggering innate immune signalling pathways) [18]. In the work reported here, we studied the biodistribution and immunological efficacy of NLc liposomes in zebrafish in vivo. We chose zebrafish as the model organism for the in vivo assays for multiple reasons: they have been widely used to study the pathogenicity of different fish and human pathogens; they have innate and adaptive immune systems; and they are easy to breed and handle [19]. We adapted a non-invasive imaging method widely used in mammalian models [20] and [21], and then used it to track the nanoliposomes in adult zebrafish in vivo. To the best of our knowledge, this is the first report of this method being applied to live zebrafish. In addition, we studied which cells were preferentially targeted by the NLc liposomes in rainbow trout (Oncorhynchus mykiss), by performing ex vivo analysis of the main immune relevant tissues. We also developed a new model for infection of adult zebrafish by the bacterium Pseudomonas aeruginosa, an opportunistic pathogen in fish and in humans [22] and [23].

The

epidemiology of rotavirus varies by setting [6]. Seasonality of infection is prominent in temperate climates while a low prevalence is maintained throughout the year in tropical countries [7]. The mode of transmission, though believed to be mainly feco-oral, is also possibly airborne and person-to-person because infection occurs in childhood irrespective of sanitary conditions [8]. Rotaviral gastroenteritis is usually accompanied by vomiting AP24534 research buy and fever and results in severe disease among infants [9]. Rotavirus is excreted in large numbers during diarrhea and the virus can remain infectious on inanimate surfaces, moist surfaces and hands. This report describes rotavirus infection detected by stool Kinase Inhibitor Library concentration testing in children followed from birth to three years of age, with sampling during and in the absence of diarrhea. This study was conducted from 2002 through 2006 in three contiguous slums in Vellore, India after approval by the institutional review board of the Christian Medical College, Vellore. The study Modulators conduct, recruitment, and sample collection methods have been published previously [10]. Briefly, a birth cohort of 452 children was followed from birth till three years of

age, analysis was restricted to the 373 children who completed three years of follow-up. Surveillance of children for rotavirus infection was done by screening bimonthly stool samples and diarrheal stool samples, and clinical data were collected to record diarrheal severity already using the Vesikari score

with scores <5 considered mild, 6–10 moderate, 11–15 severe and 16–20 very severe [11]. In case of a surveillance sample, positive samples detected by ELISA (Dako Rota IDEIA, Ely, UK) were genotyped by reverse-transcription polymerase chain reaction (RT-PCR) for VP7 and VP4 amplification while for a diarrheal sample, irrespective of the ELISA result, one sample per episode was screened using RT-PCR for VP6 before genotyping [12]. The definitions for symptomatic and asymptomatic rotavirus infections used in this study are given in Table 1. Age-specific incidence and seasonality of symptomatic and asymptomatic infections were studied. The incidence rates were obtained by Poisson regression equations and frailty models adjusted for clustering of disease/infection within a child. For cumulative incidence of rotavirus infection, Kaplan–Meier estimates of median time to infection were calculated and compared between children infected with rotavirus overall and with specific genotypes. Factors influencing rotavirus infection as well as disease rates were studied using Poisson regression. To study the risk factors for rotavirus infection, children who experienced rotavirus infection in the first year were compared to children who did not experience rotavirus infection in the first year using multiple unconditional logistic regression.

Ticks were maintained under laboratory conditions for two years prior to use in the experiments reported here. Cattle were

used to cycle the tick progeny. Tick stages requiring incubation were kept in the laboratory at 28 °C and 80% relative humidity. The Campo Grande cattle tick find more strain is susceptible to commercially available acaricides. The expressed sequence tag (EST) coding for RmLTI (GenBank ID: CK186726[21] and [24]) was optimized for P. pastoris codon usage, and synthesized by Epoch Biolabs, Inc. Codon optimization was done using Epoch Biolabs, Inc. proprietary software set at 15% cut off for codon efficiency. This RmLTI DNA fragment was cloned into pPICZαA, producing the pPICZαRmLTI construct. The recombinant plasmid codes for a His tag that is added to the N-terminus of the Libraries protein product. Previously described procedures were followed to produce rRmLTI in the P. pastoris expression system [25]. Alignment, similarity, and discordance comparisons based on bioinformatics techniques were conducted between predicted amino acid sequences for: rRmLTI, EST CK186726, BmTI-6 from ovarian cDNA (GenBank ID: P83606.2), and N-terminal amino acid sequence information for BmTI-A (GenBank ID: P83609), BmTI-D (GenBank SB431542 concentration ID: P83607), BmTI-2 (GenBank ID: P83603), and BmTI-3 (GenBank ID: P83604). ClustalW

from the BioEdit suite was used with Vector NTI® software (Invitrogen) as described previously to conduct the bioinformatics analyses [16]. The amino acid sequence from rRmLTI was submitted to protein function and superfamily analysis using the protein domains identifier software InterProScan [42]. Protein concentration in P. pastoris culture supernatant was quantified as described previously [25]. Proteins were precipitated with methanol and the precipitated proteins resuspended in denaturing binding buffer (8 M Urea, 20 mM sodium phosphate

pH 7.8, 500 mM NaCl). The rRmLTI was purified using a Ni2+ charged Ni-NTA (Qiagen, Hilden, Germany) affinity column with denaturing elution buffer (8 M Urea, 20 mM Sodium Phosphate pH 4.0, 500 mM NaCl) and the purification process monitored by 7.5% SDS-PAGE. Eluted fractions of high purity were pooled and dialyzed however against PBS. Animal care and use was conducted at EMBRAPA Beef Cattle according to institutional guidelines. Polyclonal serum against R. microplus larval extract or rRmLTI was produced using BALB/c mice as described previously [25]. The RmLTI vaccine was prepared with 500 μg of rRmLTI protein resuspended in 4 mL of 150-mM Tris–HCl at pH 7.4 and emulsified with 6 mL of Montanide ISA 61 VG (Seppic, Paris). Twelve female BALB/c mice were used, which were separated into two groups of six animals. One group received the rRmLTI formulation and the other the larval extract preparation. Each mouse within the respective group was immunized with 50 μg mL−1 dose−1 of rRmLTI, or 100 μg mL−1 dose−1 of larval extract. Three subcutaneous doses were applied at 21-day intervals.

There were 18,002 records in the laboratory database of which 17,783 could be matched with the Modulators hospital number to the CMS data and included in the analysis. The remaining

219 records were either not within the age range or could not be matched with their hospital number. In the 6M and 18Y groups, NPAs were requested on 2066 (24.8%) and 17,783 (39.4%) admissions (Appendix 7) and were positive in 6.5% (range 4.8–9.9%) and 13.2% (range 9.2–21.5%) during the 6 year period respectively (Appendix 8). Overall 1.6% of admissions in the 6M group and 5.2% in the 18Y group had a positive NPA for influenza (Appendix 7). In both age groups the highest positivity rate was in the 2009/10 period during which time the 2009 pandemic influenza A (H1NI) virus (A(H1N1)pdm09) influenza strain circulated but this effect was less marked in the 6M group Selleck HIF inhibitor (Appendix 8). In all HA hospitals the proportion of all admissions, and the proportion of admissions to general wards and intensive care units, that had a CMS diagnosis of influenza was almost double during the 2009/10 period (Appendix 9). Including all children from 0 days to below 18 years, 1993 had both a laboratory positive result and CMS diagnosis (ICD9-CM 487–487.9) of influenza (Table 1). There were an additional 359 children without a CMS diagnosis of influenza but with

a laboratory confirmed result, and 253 with a Veliparib in vitro CMS diagnosis of influenza but without laboratory confirmation. This indicates that a CMS diagnosis of influenza under-estimates disease burden relative to the laboratory results despite wide and routine laboratory testing with NPAs in children with fever or respiratory illnesses. Since there appeared to be no obvious age effect (Appendix 3) an overall mean value of 1.05 was used for adjustment factor 1 for all age groups. Of the Vasopressin Receptor 11,063 children

with a primary-respiratory associated diagnosis, 1490 did not have an NPA sent. Adjustment factor 2 assumed the influenza positive rate in these 1490 children was the same as in the 9573 children that had an NPA sent (Table 1). Again this factor did not appear to vary consistently with age and overall mean value of 1.13 was applied to all age groups (Appendix 3). Adjustment factor 3 was the proportion of all admissions by age group that had a laboratory diagnosis of influenza at PWH (Table 1). This factor varied by age group and a smoothed value excluding the first two months was applied to each monthly age group for the complete HA dataset (Appendix 3). The incidence rates of hospitalisation for influenza per 100,000 person-years based on any CMS influenza diagnosis (CMS flu) for the whole of Hong Kong were lowest in the first two months of life, then peaked between 2 and 6 months, and then declined from about 3 to 4 years of age (Fig. 2 and Fig. 3). Similar patterns were observed over the full 6 years of the study.

43. Of the cases with drusen volume regression, 30.6% (15/49) completely regressed during follow-up, whereas 69.4% (34/49) showed a decreased drusen volume only. In cases of small hard drusen with increased drusen volume, 33.9% (19/56) showed development of new drusen, whereas 66.1% (37/56) of those small hard drusen showed an increased drusen volume. Pointed drusen showed a significant

association with a progression in volume (P = .031; OR 4.89; 95% CI 1.16−20.67), with a chance of 0.80 (95% CI 0.55−0.93) for volume progression. No significant longitudinal changes were observed for dome-shaped and saw-toothed drusen. Drusen with overlying photoreceptor layer or RPE damage showed a statistically significant association with a Libraries regression in volume (P = .041; OR 7.67; 95% CI 1.09−54.24 and P = .022; OR 12.38; 95% CI 1.44−106.57), with Selleckchem Panobinostat similar chances for drusen volume regression (0.86 [95% CI 0.41−0.98] and 0.89 [95% CI 0.49−0.99], respectively). Drusen reflectivity and homogeneity did not appear to have significant impact on drusen change. In this study,

we were able to show that small hard drusen in patients with the basal laminar drusen phenotype are subject to a constant dynamic process of drusen remodeling. The initial drusen morphology seemed to predict the future course of drusen development. Small hard drusen with a decreased reflectivity of overlying RPE or photoreceptor layer were more likely to show a regression in drusen volume, whereas pointed small hard drusen were more selleck kinase inhibitor likely to show volume progression. Although the exact mechanism of drusen biogenesis in basal laminar drusen as well as in “typical” AMD is still unclear, an identical mechanism in the developmental courses may be expected because of the similar topographic, structural, and compositional features.5 In both drusen types, RPE cell pathology seems to play a major role in drusen development. Cellular remnants and debris

derived from degenerated RPE cells become sequestered between the RPE basal lamina and the inner collagenous layer of Bruch membrane and provoke a chronic inflammatory response with complement activation.34, 35 and 36 Simultaneous with this continuous process of accumulating extracellular debris, there is a process of drusen removal that may be related to at least 2 and factors. The first is the removal of these drusen constituents by macrophages.5, 10 and 37 Different types of macrophages are present in the normal human choroid.38 In contrast to resident choroidal macrophages, Bruch membrane macrophages are only seen in eyes with drusen, making these macrophages a possible player in the process of drusen regression.39 A role for macrophages in the process of drusen removal is further supported by animal models that suggest that an impaired mobilization of macrophages may prevent the clearance of drusen-like lesions in mice.

A potentially beneficial effect of higher intensity exercise on adipose tissue metabolism, such as HSL gene expression, would provide evidence for creating new guidelines of designing exercise programs in obese individuals. Thus, we tested the http://www.selleckchem.com/products/3-methyladenine.html hypothesis that caloric restriction plus vigorous-intensity aerobic exercise training would increase adipose tissue HSL gene expression to a greater extent than caloric restriction plus moderate-intensity aerobic exercise

training or caloric restriction alone in obese older women. All women were recruited from the north central area of North Carolina according to the following inclusion/exclusion criteria: (1) overweight or obese (BMI = 25–40 kg/m2 and waist girth > 88 cm), (2) older (age = 50–70 years, and at least one year without menses), (3) non-smoking, (4) not on hormone replacement therapy, (5) sedentary (<15 min of exercise, 2 times/week) in the past 6 months, and (6) weight-stable (<5% weight change) for at least 6 months prior to enrollment. The study was approved by the Wake Forest University Institutional Review Board for Human Research. All women signed informed consent to participate

in the study. Women with evidence of untreated hypertension (blood pressure > 160/90 mmHg), hypertriglyceridemia (triglyce-rides > 400 mg/dL), insulin-dependent diabetes, active cancer, liver, renal or hematological disease were excluded after an initial screening selleck screening library included a medical history review, physical examination, fasting blood profile (lipoprotein lipids, glucose, and insulin) and 12-lead resting electrocardiogram. In addition, all subjects underwent a graded treadmill exercise test to exclude those with an abnormal cardiovascular response to exercise. Fifty women were randomly assigned to either a caloric restriction alone (CR only, n = 16), CR plus moderate-intensity

exercise (CR + moderate-intensity, n = 15), Thymidine kinase or CR plus vigorous-intensity exercise (CR + vigorous-intensity, n = 19) intervention for a period of 20 weeks. This sub-study used data from the Diet, Exercise, and Metabolism for Older Women Study, a randomized completed from 2003 to 2007.15, 16, 17 and 18 Baseline measurements of body composition, metabolic variables, maximal aerobic capacity (VO2max), and adipose tissue biopsies were performed after at least 2 weeks of weight stability before the interventions. Body composition and VO2max were measured on the same day. Blood draw (for the repeated determination of metabolic variables) and fat biopsies were performed in a morning after an over-night fast, and at least 5 days after the VO2max test. The women were retested in the same manner after the 20-week interventions. The post-intervention blood draw and adipose tissue biopsies occurred at least 2 days after the last exercise session.

The mechanisms that underlie GFOs in epileptogenic conditions at early stages of development contrast with those arising in physiological MEK inhibitor conditions.

Several observations suggest that spontaneous GFOs are not present in developing networks. In rat pups, high-frequency (120–180 Hz) oscillations are observed in vivo in the hippocampus after the end of the second postnatal week (Buhl and Buzsáki, 2005). Moreover, various in vitro GFO-generating procedures or agents, such as bath application of the ACh receptor agonist carbachol of intact cortex of newborn rats (Kilb and Luhmann, 2003) or high-frequency stimulation of CA1 afferents in rat hippocampal slices (Ruusuvuori et al., 2004), failed Bosutinib manufacturer to generate GFOs during the first postnatal week. Because physiological GFOs are largely driven by glutamate in

mature networks (Bartos et al., 2007, Fisahn et al., 1998, Traub et al., 1998 and Whittington and Traub, 2003), these observations are consistent with the delayed maturation of glutamatergic synapses shown in a wide range of brain structures (Gozlan and Ben-Ari, 2003). As suggested previously (Traub et al., 1998), developing networks would lack the critical density of functional glutamatergic synapses required for these oscillatory activities. However, GFOs can emerge in epileptogenic conditions, signaling a pathological state. We showed that AMPA receptor activation is not necessary for GFO expression, and the glutamatergic drive always follows the GABAergic one in all neuron types. This is also consistent with other findings showing that synchronization of GABA neurons can occur in the absence of fast glutamatergic signaling via depolarizing GABA (Avoli and Perreault, 1987 and Michelson and Wong, 1991). Furthermore, this is also in agreement with the tetanic model of GFOs that displays comparable GABA mechanisms to the low Mg2+ model (Fujiwara-Tsukamoto et al., 2006), because it also

requires a depolarizing GABA action (Köhling et al., 2000), which is due to intracellular chloride accumulation during recurrent seizures (Dzhala et al., 2010). Although very high-frequency oscillations Methisazone (HFOs in the ripples: 140–200 Hz; fast ripples: 200–500 Hz) can be recorded in adult epileptic networks in vitro (Khosravani et al., 2005 and Traub et al., 2001) and in vivo (Jirsch et al., 2006), the GFOs recorded in our conditions never reached such frequencies during the first postnatal week, probably reflecting the immature stage of development (Buhl and Buzsáki, 2005). It has been suggested that recurrent glutamatergic synaptic transmission (Dzhala and Staley, 2004) and pyramidal axoaxonic gap junctions (Traub et al.

Similarly, P-Akt colocalized with phospho-Histone H3, a marker of M phase, in dividing apical progenitors as well as GLAST, a marker of radial glial cells (data not shown). Because these apical progenitor cells give rise to both neurons and glia, this localization is consistent with activation of AKT3 in both neurons and glia. Abnormal AKT function would be consistent with the MRI patterns and neuropathological studies ( Figures 1 and 2), which show abnormal organization MK-1775 supplier of neurons in the cortex and abnormal MRI signal characteristics of white matter. Our data suggest that activation of AKT3, either by duplication or by point mutation, contributes to hemispheric

brain overgrowth. Two of our cases (the point mutation and one partial trisomy) are confirmed to be de novo, somatic mutations, undetectable in blood, and although nonbrain tissues were not available from the other partial trisomy case, this is likely

to be a somatic mutation as well, because http://www.selleckchem.com/products/Imatinib-Mesylate.html individuals reported with constitutional trisomy 1q, even a portion of 1q, show dysmorphic features and, in nearly all cases, early lethality ( Mark et al., 2005, Mefford et al., 2008 and Patel et al., 2009). We postulate that increasing AKT3 dosage and activation of AKT3 would have the same effect in the setting of a somatic mutation. Interestingly, HMG has not been reported in the constitutional trisomy cases, even those that have partial trisomy including AKT3. It is possible that HMG might not be present in the cases with early lethality; perhaps more important, because all of the constitutional trisomy 1q cases were de novo, the trisomy may not be present in all tissues. Though we have not sampled other tissues, there was no clinical evidence of extracerebral involvement phenotypically in any of the three cases, suggesting that either the mutation was limited to the brain or activation of AKT3 in other tissues does not have phenotypic consequences. Increased rates of brain cancer are not reported new in the setting

of isolated HMG. In the cases we report here, which have not shown any form of cancer, it is likely that activation of AKT3 disrupts normal cortical development but does not result in continued dysregulated growth outside the setting of cortical progenitor cells. Further support for the role of AKT3 in controlling brain size comes from animal studies. A mouse Akt3 knockout model shows selective reduction in brain size due to decreased neuronal number and size ( Easton et al., 2005), whereas mice with an activating mutation in the kinase domain of Akt3 show larger hippocampal size and abnormal Ki67-positive ectopic neurons in the hippocampus ( Tokuda et al., 2011). Additionally, in zebrafish, overexpression of wild-type akt3 produces increased embryonic brain thickness ( Chen et al., 2011). All of these results strongly suggest that AKT3 activity dynamically regulates brain size and that increased dosage of AKT3 might increase brain size in humans.

Radioligand binding assays of mu opioid receptors, for example, detect little downregulation in most brain regions even after prolonged administration of agonist drugs (Sim-Selley et al., 2000; Yoburn et al., 1993). Instead, it is thought that the major trafficking itinerary of receptors after ligand-induced endocytosis is nondestructive recycling to the plasma membrane, which can occur

repeatedly and efficiently under conditions of prolonged agonist exposure (Tanowitz and von Zastrow, 2003) (Figure 1B). 7TMR recycling has long been recognized to be one means for supporting the ability of cells to sustain cellular responsiveness to a neuromodulator or for achieving efficient recovery of responsiveness after a period of functional desensitization (Gainetdinov et al., 2004). LGK-974 manufacturer An important caveat is that most studies investigating the functional consequences of 7TMR recycling are limited to cultured cell systems. However, the rapid recycling pathway traversed by adrenergic catecholamine receptors is essential for maintaining physiological catecholamine responsiveness of the heart (Odley et al., 2004). Conversely,

disrupting the ability of mu opioid receptors to recycle efficiently signaling pathway in vivo produces enhanced physiological tolerance to the antinociceptive effects of opioids (Enquist et al., 2011). Differences in the endocytic trafficking fate of otherwise similar 7TMRs can confer essentially opposite functional effects on longer-term cellular signaling responsiveness (Cao et al., 1999; Tanowitz and von Zastrow, 2003). In principle, discrete endocytic fates could be mediated by altogether different endocytic mechanisms or by molecular sorting of receptors after endocytosis. The former possibility has not been fully ruled out and may apply to the oxyclozanide regulation of some 7TMRs. However, there is compelling

evidence that opioid and catecholamine receptors are subject to exquisitely selective molecular sorting after endocytosis by a shared, CCP-dependent early endocytic pathway (Tsao and von Zastrow, 2000; Puthenveedu et al., 2010). The following discussion will focus on such “postendocytic” sorting of 7TMRs and the recycling-versus-degradation decision as a relatively extensively studied example. Many signaling receptors require ubiquitylation for endocytic delivery to lysosomes and recycle efficiently to the plasma membrane when their ubiquitylation is prevented (Raiborg and Stenmark, 2009; Eden et al., 2012). Ubiquitin-directed sorting is mediated by a complex endosome-associated machinery, extensively conserved from yeast to humans, which is collectively called the endosomal sorting complex required for transport (ESCRT, Figure 2A). A great deal is presently known about ESCRT structure and function, as discussed in excellent recent reviews (Hurley and Hanson, 2010; Henne et al., 2011; Raiborg and Stenmark, 2009).