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The nociceptive network, responsible for transmission of nociceptive signals that generate the pain experience, is not fully developed at birth. Descending serotonergic modulation of spinal nociception, an important part of the pain network, undergoes substantial postnatal maturation and is suggested to be involved in the altered pain response observed in human newborns. This review summarizes preclinical data of the development of descending serotonergic modulation of the spinal nociceptive network across the life span, providing a comprehensive background to understand human newborn pain experience and treatment. Sprouting of descending serotonergic axons, originating from the rostroventral medulla, as well as changes in receptor function and expression take place in the first postnatal weeks of rodents, corresponding to human neonates in early infancy. Descending serotonergic modulation switches from facilitation in early life to bimodal control in adulthood, masking an already functional 5-HT inhibitory system at early ages. Specifically the 5-HT3 and 5-HT7 receptors seem distinctly important for pain facilitation at neonatal and early infancy, while the 5-HT1a, 5-HT1b, and 5-HT2 receptors mediate inhibitory effects at all ages. Analgesic therapy that considers the neurodevelopmental phase is likely to result in a more targeted treatment of neonatal pain and may improve both short- and long-term effects. Impact: The descending serotonergic system undergoes anatomical changes from birth to early infancy, as its sprouts and descending projections increase and the dorsal horn innervation pattern changes.Descending serotonergic modulation from the rostral ventral medulla switches from facilitation in early life via the 5-HT3 and 5-HT7 receptors to bimodal control in adulthood.A functional inhibitory serotonergic system mainly via 5-HT1a, 5-HT1b, and 5-HT2a receptors at the spinal level exists already at the neonatal phase but is masked by descending facilitation.

The influence of neonatal experiences upon later-life affective behavior is increasingly recognized, but the reported effects on anxiety are often contradictory. The observed effect may depend upon the type of anxiety (state or trait) affected. The current study aims to investigate whether neonatal repetitive needle pricking alters anxiety behavior in adulthood, by assessing both state and trait anxiety in rats. Sprague–Dawley rat pups received four unilateral needle pricks per day, while controls received four tactile stimuli or were left completely undisturbed during the first postnatal week. Mechanical sensitivity was assessed in the neonatal phase and throughout the development. State anxiety was assessed in the open field test and trait anxiety in the elevated zero maze. The results show that repetitive needle pricking leads to acute mechanical hypersensitivity, but does not affect baseline mechanical sensitivity throughout development. In adulthood, animals previously exposed to neonatal procedural pain (including repetitive handling and removal from litter) showed lower state anxiety but did not differ in trait anxiety, as compared with the undisturbed controls. These findings indicate that early-life procedural pain decreases state but not trait anxiety behavior in later life in a rodent model of repetitive needle pricking.

A growing body of evidence indicates that early-life exposure to selective serotonin reuptake inhibitor has long-term consequences on the offspring's pain in addition to affective disorders like anxiety disorder and major depression. Serotonin, besides its role in regulating pain and emotions, promotes neuronal network formation. The prefrontal cortex and the amygdala are two key brain regions involved in the modulation of pain and its affective comorbidities. Thus, the aim of this review is to understand how early-life selective serotonin reuptake inhibitor exposure alters the developing prefrontal cortex and amygdala and thereby underlies the long-term changes in pain and its affective comorbidities in later life. While there is still limited data on the effects of early-life selective serotonin reuptake inhibitor exposure on pain, there is a substantial body of evidence on its affective comorbidities. From this perspective paper, four conclusions emerged. First, early-life selective serotonin reuptake inhibitor exposure results in long-term nociceptive effects, which needs to be consistently studied to clarify. Second, it results in enhanced depressive-like behaviour and diminished exploratory behaviour in adult rodents. Third, early-life selective serotonin reuptake inhibitor exposure alters serotonergic levels, transcription factors expression, and brain-derived neurotrophic factor levels, resulting in hyperconnectivity within the amygdala and the prefrontal cortex. Finally, it affects antinociceptive inputs of the prefrontal cortex and the amygdala in the spinal cord. We conclude that early-life selective serotonin reuptake inhibitor exposure affects the maturation of prefrontal cortex and amygdala circuits and thereby enhances their antinociceptive inputs in the spinal cord.

The Ngorongoro Conservation Area (NCA) is a protected area and UNESCO World Heritage Site and part of the Serengeti‐Ngorongoro Biosphere reserve in northern Tanzania. It is famous for its large volcanic caldera, unique cultural heritage, early hominid fossils and significant wildlife populations. NCA has been managed as a multiple land‐use area since 1959, a designation intended to foster a harmonious coexistence between indigenous residents and wildlife (Goldstein, 2004).

Social dynamics are of fundamental importance in animal societies. Studies on nonhuman animal social systems often aggregate social interaction event data into a single network within a particular time frame. Analysis of the resulting network can provide a useful insight into the overall extent of interaction. However, through aggregation, information is lost about the order in which interactions occurred, and hence the sequences of actions over time. Many research hypotheses relate directly to the sequence of actions, such as the recency or rate of action, rather than to their overall volume or presence. Here, we demonstrate how the temporal structure of social interaction sequences can be quantified from disaggregated event data using the relational event model (REM). We first outline the REM, explaining why it is different from other models for longitudinal data, and how it can be used to model sequences of events unfolding in a network. We then discuss a case study on the European jackdaw, Corvus monedula, in which temporal patterns of persistence and reciprocity of action are of interest, and present and discuss the results of a REM analysis of these data. One of the strengths of a REM analysis is its ability to take into account different ways in which data are collected. Having explained how to take into account the way in which the data were collected for the jackdaw study, we briefly discuss the application of the model to other studies. We provide details of how the models may be fitted in the R statistical software environment and outline some recent extensions to the REM framework.

Bird song is a sexually selected signal that serves two main functions, attracting a mate and deterring rivals. Different signal parameters may be important in advertising to females compared to advertising to rival males. Species solve the problem of this dual function in a variety of ways, one of which may be to have separate parts of song directed at male and female receivers. The blackcap song has two distinct parts, a complex warble, assumed to be directed at female receivers, followed by a louder and more stereotyped whistle putatively directed at males. We simulated territorial intrusions by broadcasting blackcap song in territories. Comparing songs sung prior, with those produced in response to playback, showed that the proportion of the whistle component of songs increased, but not the warble. This study thus provides empirical evidence that the whistle component of the blackcap song plays a prominent role in male–male competition. The warble component of the blackcap song may be directed at females, but this requires further testing.

Little is known about the role of maternal nutrition in the development of hypospadias, which is the most common urogenital congenital anomaly. This study investigated the relationship between maternal nutrition and the risk of hypospadias, particularly focusing on maternal food patterns. We compared 471 hypospadias cases with 490 controls in the United Kingdom. A questionnaire including information on life style, occupation, usual maternal diet and dietary supplements was administered using telephone interviews. Cases and controls were compared for individual food item intake and food patterns derived by cluster analysis. Multivariable logistic regression analysis adjusted for income, maternal age, low birthweight, smoking and folic acid supplement use was used to assess the relationship between maternal nutrition and hypospadias. Three food patterns were created with the labels 'health conscious', 'mixed' and 'non-health conscious'. 'Non-health conscious' subjects (low frequency of consumption of yoghurt, cheese, eggs, fruit and vegetables, fish, beans and pulses, olive oil and organic food) had a higher risk of hypospadias (odds ratio 1.54; 95% confidence interval 1.06, 2.26) compared with 'health conscious' subjects (high frequency of consumption of fresh fruit and vegetables, dried fruit, fresh or frozen fish, beans, pulses, soya products, olive oil and organic food), after adjustment for potential confounders. Intakes of individual foods were not strongly associated with hypospadias. We could not exclude the possibility of residual confounding, and this needs to be further investigated. We found an association between food pattern and hypospadias, with those with less health conscious food patterns having a higher risk. Further study is needed to confirm this association.

A new noise-figure measurement method, which combines the simplicity of the "classical" Y-factor method with the accuracy of the widely used "cold noise-source" method, is reported. Implemented in our fully automated wide-band 1-18-GHz on-wafer noise-parameter measurement system, accurate results are obtained using a small set of precharacterized source impedances. We illustrate our method and its accuracy with data taken on a low-noise GaAs pseudomorphic high electron-mobility transistor device, and quantify the impact of the instrumental uncertainties on the extracted noise parameters.

This paper presents a new method, developed for the capacitance–voltage (C–V) characterization of leaky dielectrics. The method comprises measurements in the gigahertz range on specially designed RF test structures. The method is verified against high-frequency C–V measurements on NMOS and PMOS structures. It yields reliable results even when the gate leakage is in excess of 100 A/cm2.

Most bird species produce different acoustic signals in different behavioural contexts. This intraspecific variation in signal types is thought to be the result of selection for optimal communication in each context. Doves in the genus Streptopelia have three distinct behavioural contexts in which they produce coo vocalizations. Some Streptopelia species have three acoustically similar coo vocalizations associated with the three contexts, but in others the coo vocalizations differ in acoustic structure. Using a well-resolved phylogeny, we examined whether acoustic differentiation between coo types was the ancestral state. Unexpectedly, the results showed that the common ancestor of Streptopelia had differentiated coos rather than a single coo type. This result implies that context-specific acoustic signals disappeared from the vocal repertoire independently at least two times. We further tested whether different context-dependent signal types follow different evolutionary pathways and whether they differ in rate of evolutionary change. We found that the long-range signal (perch-coo) evolves at a higher rate than the short-range signal (bow-coo). These results are discussed in relation to selection for species recognition and transmission requirements.

A low-temperature scanning tunneling microscope has been used to study the (110)-cleavage surface of indium phosphide (InP) at 4.2 K. InP is a III-V compound semiconductor, and we studied the behavior of doping atoms at different bias voltages in both n- and p-type InP. In neither the n- nor the p-type InP did we observe Friedel oscillations, but the p-type InP with a Zn-dopant concentration of 2.7 x 10 18 cm -3 showed an interesting behavior at positive sample voltages: upon moving the tip Fermi level to the bottom of the conduction band, we observed that depressions in the surface topography caused by the influence of the Zn doping atoms changed into elevations with a triangular shape. This has previously been observed on p-type GaAs(110), and an explanation for these triangular features is not yet available.

We present a MOS Capacitance-Voltage measurement methodology that, contrary to present methods, is highly robust against gate leakage current densities up to 1000 A/cm/sup 2/. The methodology features specially designed RF test structures and RF measurement frequencies. It allows MOS parameter extraction in the full range of accumulation, depletion, and inversion.

We have optimized 3 key RF devices realized in standard logic 90 nm CMOS technology and report a record performance in terms of n-MOS maximum oscillation frequency f/sub max/ (280 GHz), varactor tuning range and varactor and inductor quality factor.

SiGe:C heterojunction bipolar transistors (HBTs) offer high cut-off frequencies, f/sub T/, but low open base breakdown voltages, BV/sub CEO/, due to the relatively high current gain, h/sub FE/. In this paper, we show that the integration of a metal emitter, made by complete silicidation of a mono-emitter, increases the base current, I/sub B/ without reducing the collector current, I/sub C/. Hence, the BV/sub CEO/ is increased without affecting the f/sub T/. Furthermore, this metal emitter reduces the emitter series resistance, R/sub E/, and increases the f/sub T/ compared with a mono-emitter. SiGe:C HBTs with f/sub T/=230GHz and BV/sub CEO/=1.8V have been realised using a metal emitter in a self-aligned integration scheme.

We study the noise behaviour of bipolar transistors for collector voltages close to and beyond the collector-emitter breakdown voltage. We model the excess noise due to amplification of shot noise and due to the impact ionisation itself, both for weak avalanche and for strong avalanche. Our new model accurately predicts the measurements, without the need for parameter fitting to noise data.

A highly accurate predictive inductor model for integrated symmetric inductors with center tap and patterned ground shield is presented. This model is based on a modified Greenhouse algorithm where current crowding due to skin and proximity effects is included by considering the spread in parallel sub-loop inductances. This scalable symmetrical inductor equivalent circuit model covers all operating conditions, and yet only requires dimensions and back-end layer thicknesses. We have verified this scalable model for a large number of inductors from three industrial IC processes and found excellent agreement with measured inductances, Q-factors, and resonance frequencies.

We present an MOS capacitance-voltage measurement methodology that, contrary to present methods, is highly robust against gate leakage current densities up to 1000 A/cm/sup 2/. The methodology features specially designed RF test structures and RF measurement frequencies. It allows MOS parameter extraction in the full range of accumulation, depletion, and inversion.

The thermal noise of short-channel NMOS transistors in a commercially available 0.13 -mm CMOS technology is studied. The experimental results are modelled with a non-quasi- static RF model, based on the principle of channel segmentation. The model is capable of predicting both drain and gate current noise accurately, without fitting any parameters to the measured noise data. An essential ingredient of the model is the gate resistance, which is shown to dominate the gate current noise. In the optimised device layouts, this gate resistance is mainly determined by the silicide-to-polysilicon contact resistance. The ever-continuing downscaling of CMOS technologies has resulted in a strong improvement in the RF perfor- mance of MOS devices (1-3). Consequently, CMOS has become a viable option for analogue RF applications and RF system-on-chip. For the application of modern CMOS technologies in low-noise RF circuits, accurate modelling of noise is a prerequisite. In MOSFETs, there are two intrinsic sources of noise: 1/f noise and thermal noise, the latter being the topic of this paper. Thermal noise is due to the random thermal motion of charge carriers. It not only manifests itself in the drain current noise spectrum, but, due to the capacitive coupling between channel and gate, also in the gate current noise spectrum. The latter effect is known as 'induced gate noise'. In addition to the intrinsic MOSFET thermal noise, the parasitic resistances (gate resistance, bulk resistance, and source/drain resistances) also exhibit thermal noise. Thermal noise of deep-submicron MOSFETs has received considerable attention lately, triggered by publica- tions reporting a strong enhancement of thermal noise with respect to long-channel theory (4-8). In the earliest of these publications (4), thermal noise was found to be enhanced by a factor upto 12 in n-channel devices with gate length 0.7mm, and hot electrons were proposed to explain these results. More recently, Klein (5, 6) reported very similar enhancement of drain current thermal noise in devices with gate length 0.65mm and proposed a model that invokes heating of the charge carriers in the inversion channel to explain the experiments. For the induced gate noise, an even more dramatic enhancement factor as large as 30 was found by Knoblinger (7) for a 0.25 -mm gate length n-channel MOSFET. Evidently, these reported noise enhancements would seriously limit the viability of RF CMOS, and a detailed study is called for. In previous work (9-11), in sharpcontrast to the above- mentioned authors, only moderate enhancement of the MOSFET drain current thermal noise was found, mainly caused by parasitic resistances and channel length modula- tion. This was found for 0.35 -mm, 0.25 -mm, and 0.18 -mm CMOS technologies. MOSFET gate current thermal noise, on the other hand, was found to be enhanced more severely. This enhancement could be traced back to the effects of gate resistance, and the silicide-to-polysilicon contact resistance in particular. Although the thermal noise, as found in CMOS fabrication down to 0.18mm, seems fairly well understood, it remains important to study the phenomenon for more advanced CMOS technologies: it seems probable that at some point down the ITRS roadmap, the main assumption of our theory, i.e. thermal equilibrium, will break down. Therefore, in this work (which was reported earlier in (12)), we extend our study of MOSFET thermal noise to 0.13 -mm technology. We present a large number of new experimental results in the 1-18 GHz frequency range, and compare them with the predictions of our previously developed RF MOSFET model.