BACKGROUND

A globally harmonized protocol (HarP) for manual hippocampal segmentation based on magnetic resonance has been recently developed by a task force from European Alzheimer's Disease Consortium (EADC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Our aim was to produce benchmark labels based on the HarP for manual segmentation.

METHODS

Five experts of manual hippocampal segmentation underwent specific training on the HarP and segmented 40 right and left hippocampi from 10 ADNI subjects on both 1.5 T and 3 T scans. An independent expert visually checked segmentations for compliance with the HarP. Descriptive measures of agreement between tracers were intraclass correlation coefficients (ICCs) of crude volumes and similarity coefficients of three-dimensional volumes.

RESULTS

Two hundred labels have been provided for the 20 magnetic resonance images. Intra- and interrater ICCs were >0.94, and mean similarity coefficients were 1.5 T, 0.73 (95% confidence interval [CI], 0.71-0.75); 3 T, 0.75 (95% CI, 0.74-0.76).

CONCLUSIONS

Certified benchmark labels have been produced based on the HarP to be used for tracers' training and qualification.

The propulsive motions of swimming harp seals (Phoca groenlandica Erxleben) and ringed seals (Phoca hispida Schreber) were studied by filming individuals in a flume. The seals swam at velocities ranging from 0.6 to 1.42 m s-1. Locomotion was accomplished with alternate lateral sweeps of the hind flippers generated by lateral flexions of the axial body in conjunction with flexion of the flippers. The frequency of the propulsive cycle increased linearly with the swimming velocity, and the maximum angle of attack of the flipper decreased, but the amplitude remained constant. The kinematics and morphology of this hind flipper motion indicated that phocid seals do not swim in the carangiform mode as categorized by Lighthill (1969), but in a distinct mode that mimics swimming by thunniform propulsors. The hind flippers acted as hydrofoils, and the efficiency, thrust power and coefficient of thrust were calculated from unsteady wing theory. The propulsive efficiency was high at approximately 0.85. The thrust power increased curvilinearly with velocity. The drag coefficient ranged from 0.012 to 0.028 and was found to be 2.8-7.0 times higher than the theoretical minimum. The drag coefficient was high compared with that of phocid seals examined during gliding or towing experiments, indicating an increased drag encumbered by actively swimming seals. It was determined that phocid seals are capable of generating sufficient power for swimming with turbulent boundary layer conditions.

This commentary introduces the HARPS supplement on getting research into policy and practice in sexual and reproductive health (SRH). The papers in this supplement have been produced by the Sexual Health and HIV Evidence into Practice (SHHEP) collaboration of international research, practitioner and advocacy organizations based in research programmes funded by the UK Department for International Development.The commentary describes the increasing interest from research and communication practitioners, policy makers and funders in expanding the impact of research on policy and practice. It notes the need for contextually embedded understanding of ways to engage multiple stakeholders in the politicized, sensitive and often contested arenas of sexual and reproductive health. The commentary then introduces the papers under their respective themes: (1) The theory and practice of research engagement (two global papers); (2) Applying policy analysis to explore the role of research evidence in SRH and HIV/AIDS policy (two papers with examples from Ghana, Malawi, Uganda and Zambia); (3) Strategies and methodologies for engagement (five papers on Kenya, South Africa, Ghana, Tanzania and Swaziland respectively); (4) Advocacy and engagement to influence attitudes on controversial elements of sexual health (two papers, Bangladesh and global); and (5) Institutional approaches to inter-sectoral engagement for action and strengthening research communications (two papers, Ghana and global).The papers illustrate the many forms research impact can take in the field of sexual and reproductive health. This includes discursive changes through carving out legitimate spaces for public debate; content changes such as contributing to changing laws and practices, procedural changes such as influencing how data on SRH are collected, and behavioural changes through partnerships with civil society actors such as advocacy groups and journalists.The contributions to this supplement provide a body of critical analysis of communication and engagement strategies across the spectrum of SRH and HIV/AIDS research through the testing of different models for the research-to-policy interface. They provide new insights on how researchers and communication specialists can respond to changing policy climates to create windows of opportunity for influence.

Development of left ventricular (LV) remodeling after acute myocardial infarction (AMI) is a serious medical complication. We investigated the correlation of LV dyssynchrony after AMI with LV remodeling using magnetic resonance-myocardial tagging (MR-MT) derived dyssynchrony index (circumferential uniformity ratio estimate [CURE]). Forty-three patients diagnosed with ST-elevation AMI were analyzed. After treatment with primary percutaneous intervention, cardiac magnetic resonance imaging was performed to obtain a cine image, a delayed enhancement image, and an MR-MT image. CURE as a dyssynchrony index was calculated from the MR-MT image using HARP software (CURE 0 to 1 = dyssynchrony to synchrony). After 6 months, follow-up cardiac magnetic resonance imaging was performed to assess degree of LV remodeling. Sixteen patients (37%) had an increased LV end-systolic volume (ESV) >15% compared with baseline. The baseline LV dyssynchrony index, CURE, was significantly associated with ESV at 6 months (r = -0.49, p <0.001) and weakly correlated with change in ESV (percentage) compared with baseline values (r = -0.26, p = 0.08). Multivariate analysis showed that CURE was associated only with change in ESV (beta -0.39, p = 0.03). Subgroup analysis for patients with nonviable myocardium (infarct thickness >75%, n = 31) showed that this correlation was stronger (beta -0.52, p = 0.006), suggesting that CURE could predict progression of LV remodeling in patients with AMI and nonviable myocardium. LV dyssynchrony immediately after AMI is an important determinant of LV remodeling. In conclusion, the MR-MT dyssynchrony index, CURE, might be useful for prediction of LV remodeling in patients with AMI.

Bed rest deconditioning leads to physiological cardiac atrophy, which may compromise left ventricular (LV) filling during orthostatic stress by reducing diastolic untwisting and suction. To test this hypothesis, myocardial-tagged magnetic resonance imaging (MRI) was performed, and maximal untwisting rates of the endocardium, midwall, and epicardium were calculated by Harmonic Phase Analysis (HARP) before and after -6 degrees head-down tilt bed rest for 18 days with (n = 14) and without exercise training (n = 10). LV mass and LV end-diastolic volume were measured using cine MRI. Exercise subjects cycled on a supine ergometer for 30 min, three times per day at 75% maximal heart rate (HR). After sedentary bed rest, there was a significant reduction in maximal untwisting rates of the midwall (-46.8 +/- 14.3 to -35.4 +/- 12.4 degrees /s; P = 0.04) where untwisting is most reliably measured, and to a lesser degree of certainty in the endocardium (-50.3 +/- 13.8 to -40.1 +/- 18.5 degrees /s; P = 0.09); the epicardium was unchanged. In contrast, when exercise was performed in bed, untwisting rates were enhanced at the endocardium (-48.4 +/- 20.8 to -72.3 +/- 22.3 degrees /ms; P = 0.05) and midwall (-39.2 +/- 12.2 to -59.0 +/- 19.6 degrees /s; P = 0.03). The differential response was significant between groups at the endocardium (interaction P = 0.02) and the midwall (interaction P = 0.004). LV mass decreased in the sedentary group (156.4 +/- 30.3 to 149.5 +/- 27.9 g; P = 0.07), but it increased slightly in the exercise-trained subjects (156.4 +/- 34.3 to 162.3 +/- 40.5 g; P = 0.16); (interaction P = 0.03). We conclude that diastolic untwisting is impaired following sedentary bed rest. However, exercise training in bed can prevent the physiological cardiac remodeling associated with bed rest and preserve or even enhance diastolic suction.

Parasite-mediated sexual selection theory presumes that variation in sexual traits reliably reflects variation in parasite resistance among available mates. One mechanism that may warrant signal honesty involves costs of immune system activation in the case of a parasitic infection. We investigated this hypothesis in male field crickets Gryllus campestris, whose attractiveness to females depends on characteristics of the sound-producing harp that are essentially fixed following adult eclosion. During the nymphal stage, males subjected to one of two feeding regimes were challenged with bacterial lipopolysaccharides (LPS) to investigate condition-dependent effects on harp development as compared to other adult traits. Nymphal nutritional status positively affected adult body size, condition, and harp size. However, nymphal immune status affected harp size only, with LPS-males having smaller harps than control-injected males. In addition, the harps of LPS-males showed a lesser degree of melanization, indicating an enhanced substrate use by the melanin-producing enzyme cascade of the immune system. Thus, past immune status is specifically mirrored in sexual traits, suggesting a key role for deployment costs of immunity in parasite-mediated sexual selection.

Hematological and blood chemistry values were examined in harp seals (Pagophilus groenlandicus) exposed to daily oral dosages of methylmercuric chloride (MMC). Two seals, exposed to 0.25 mg MMC/kg body weight/day for 60 and 90 days, respectively, did not show abnormal blood values. Two other seals exposed to 25.0 mg MMC/kg body weight/day died on day 20 and 26 of exposure. Blood parameters indicated toxic hepatitis, uremia and renal failure. Total mercury and methylmercury values in the tissues of the experimental animals indicated that harp seals can tolerate high levels of mercury in the brain and that the observed renal and hepatic dysfunction were related to the high accumulation of mercury in these tissues. Tests of renal function are useful in cases of severe methylmercury poisoning.

BACKGROUND

In the past few years, there has been controversy over the relationship between suicidal behavior and fluoxetine use. This report examines the relationship between fluoxetine use and suicidal behavior in the Harvard/Brown Anxiety Disorders Research Program (HARP).

METHODS

HARP is a naturalistic, prospective, longitudinal anxiety disorders study. Probabilities of suicidal behavior for 654 subjects were examined using life table analysis for the study group as a whole and stratified by depression status at intake.

RESULTS

Subjects not using fluoxetine during follow-up had almost twice the probability of making a suicide attempt or gesture during the follow-up than subjects who were using fluoxetine, although this difference was not statistically significant. Subjects having episodes of major depressive disorder (MDD) at intake were more likely than those not having an episode to receive fluoxetine during follow-up (74/166 [45%] vs. 118/488 [24%], chi squared= 24.85, df= 1, p < .0001). Among those subjects having episodes of MDD at intake, there was a statistically significantly lower probability of suicide attempts/gestures for those taking fluoxetine than for those not using fluoxetine during follow-up (log-rank chi squared= 5.10, df= 1, p= .02).

CONCLUSIONS

We found no evidence that fluoxetine use is associated with increased risk of suicide attempts or gestures. However, we did find that subjects with more suicide risk factors at intake were more likely to use fluoxetine than those without these risk factors.

Two-dimensional (2-D) strain fields were estimated non-invasively in two simple experimental models of closed-head brain injury. In the first experimental model, shear deformation of a gel was induced by angular acceleration of its spherical container In the second model the brain of a euthanized rat pup was deformed by indentation of its skull. Tagged magnetic resonance images (MRI) were obtained by gated image acquisition during repeated motion. Harmonic phase (HARP) images corresponding to the spectral peaks of the original tagged MRI were obtained, following procedures proposed by Osman, McVeigh and Prince. Two methods of HARP strain analysis were applied, one based on the displacement of tag line intersections, and the other based on the gradient of harmonic phase. Strain analysis procedures were also validated on simulated images of deformed grids. Results show that it is possible to visualize deformation and to quantify strain efficiently in animal models of closed head injury.

OBJECTIVE

To quantify periodic displacement in the cranium using complementary spatial modulation of magnetization (CSPAMM) with harmonic phase (HARP) postprocessing.

METHODS

CSPAMM tagging sequence with separate tag-line preparation in two orthogonal directions was applied on 10 healthy volunteers in combination with HARP for tissue displacement mapping.

RESULTS

Important features of brain dynamics, such as caudal displacement amplitude and the time-to-peak of the pulse wave were derived for six regions in the brain. Peak displacement values amounted to 0.18+/-0.02 mm, 0.10+/-0.01 mm, 0.09+/-0.02 mm, and 0.04+/-0.01 mm for regions in the pons, cerebellum, corpus callosum (splenium), and frontal lobe, respectively. Displacement values of the pons differed significantly from all other regions measured. With the additional information of the time-to-peak measure all six regions except the corpus callosum (splenium) and cerebellum can be distinguished. The values found suggest that the pulse wave travels from the brain stem first occipitally and then to the frontal lobe, where peak values appear later and are significantly attenuated.

CONCLUSIONS

Direct quantification of periodic caudal brain tissue displacement is feasible with the proposed method, and several brain regions can be distinguished through peak displacement and time-to-peak values.

An indirect flat-panel imager (FPI) with avalanche gain is being investigated for low-dose x-ray imaging. It is made by optically coupling a structured x-ray scintillator CsI(Tl) to an amorphous selenium (a-Se) avalanche photoconductor called HARP (high-gain avalanche rushing photoconductor). The final electronic image is read out using an active matrix array of thin film transistors (TFT). We call the proposed detector SHARP-AMFPI (scintillator HARP active matrix flat panel imager). The advantage of the SHARP-AMFPI is its programmable gain, which can be turned on during low dose fluoroscopy to overcome electronic noise, and turned off during high dose radiography to avoid pixel saturation. The purpose of this paper is to investigate the important design considerations for SHARP-AMFPI such as avalanche gain, which depends on both the thickness d(Se) and the applied electric field E(Se) of the HARP layer. To determine the optimal design parameter and operational conditions for HARP, we measured the E(Se) dependence of both avalanche gain and optical quantum efficiency of an 8 microm HARP layer. The results were used in a physical model of HARP as well as a linear cascaded model of the FPI to determine the following x-ray imaging properties in both the avalanche and nonavalanche modes as a function of E(Se): (1) total gain (which is the product of avalanche gain and optical quantum efficiency); (2) linearity; (3) dynamic range; (4) gain nonuniformity resulting from thickness nonuniformity; and (5) effects of direct x-ray interaction in HARP. Our results showed that a HARP layer thickness of 8 microm can provide adequate avalanche gain and sufficient dynamic range for x-ray imaging applications to permit quantum limited operation over the range of exposures needed for radiography and fluoroscopy.

SMARCAL1, a DNA remodeling protein fundamental to genome integrity during replication, is the only gene associated with the developmental disorder Schimke immuno-osseous dysplasia (SIOD). SMARCAL1-deficient cells show collapsed replication forks, S-phase cell cycle arrest, increased chromosomal breaks, hypersensitivity to genotoxic agents, and chromosomal instability. The SMARCAL1 catalytic domain (SMARCAL1(CD)) is composed of an SNF2-type double-stranded DNA motor ATPase fused to a HARP domain of unknown function. The mechanisms by which SMARCAL1 and other DNA translocases repair replication forks are poorly understood, in part because of a lack of structural information on the domains outside of the common ATPase motor. In the present work, we determined the crystal structure of the SMARCAL1 HARP domain and examined its conformation and assembly in solution by small angle X-ray scattering. We report that this domain is conserved with the DNA mismatch and damage recognition domains of MutS/MSH and NER helicase XPB, respectively, as well as with the putative DNA specificity motif of the T4 phage fork regression protein UvsW. Loss of UvsW fork regression activity by deletion of this domain was rescued by its replacement with HARP, establishing the importance of this domain in UvsW and demonstrating a functional complementarity between these structurally homologous domains. Mutation of predicted DNA-binding residues in HARP dramatically reduced fork binding and regression activities of SMARCAL1(CD). Thus, this work has uncovered a conserved substrate recognition domain in DNA repair enzymes that couples ATP-hydrolysis to remodeling of a variety of DNA structures, and provides insight into this domain's role in replication fork stability and genome integrity.

OBJECTIVE

This investigation examines the prevalence and characteristics of medical illness in 711 patients enrolled in the Harvard/Brown Anxiety Disorders Research Program (HARP), a multi-center, longitudinal study of anxiety disorders.

METHODS

Eligible subjects were those with present or past index anxiety disorders: panic disorder without agoraphobia, panic disorder with agoraphobia, agoraphobia without panic disorder, social phobia, or generalized anxiety disorder. They were assessed by trained raters using structured diagnostic interviews and the Medical History Form II.

RESULTS

Patients with panic disorder and co-morbid major depressive disorder had significantly higher rates of reported medical illness than anxiety disorder patients without depression. When the rates of medical illness for all subjects were compared with those from the Rand Health Insurance Experiment, we found the prevalence of several medical problems to be disproportionately increased.

CONCLUSIONS

Although our results are preliminary, it appears that patients with panic disorder have more reported medical problems than the public at large, in particular, more ulcer disease, angina, and thyroid disease. Somatic complaints in patients with panic disorder, therefore, need to be carefully considered.

In previous work, we isolated 7 neuroprotective iridoid glycosides from the 90% MeOH fraction of Scrophularia buergeriana (Scrophulariaceae). We therefore investigated the mode of action of 8-O-E-p-methoxycinnamoyl-harpagide (8-MCA-Harp), the most potent neuroprotective iridoid, and its aglycone, harpagide (Harp) using primary cultures of rat cortical cells in vitro. 8-MCA-Harp only revealed its neuroprotective activity in a pretreatment paradigm; this iridoid had more selectivity in protecting neurons against N-methyl-D-aspartate (NMDA)-induced neurotoxicity as opposed to that induced by kainic acid (KA). On the other hand, Harp exerted significant neuroprotective activity when it was administered either before or after glutamate insult and protected cultured neuronal cells from neurotoxicity induced by NMDA or KA. Furthermore, Harp significantly prevented the decrease of glutathione, an antioxidative compound in the brain, in our cultures. Finally, 8-MCA-Harp and Harp could successfully reduce the overproduction of nitric oxide and the level of cellular peroxide in cultured neurons. Collectively, these results suggested that Harp and 8-MCA-Harp protected primary cultured neurons against glutamate-induced oxidative stress primarily by acting on the antioxidative defense system and on glutamatergic receptors, respectively.

BACKGROUND

The development and growth of human prostate cancer is mediated by many tumor cell-derived growth factors. Heparin affin regulatory peptide (HARP) seems to be involved in the progression of several tumors of diverse origin. In the present study, we sought to determine if HARP is implicated in human prostate cancer.

METHODS

An antisense strategy for inhibition of HARP expression in the human prostate cancer cell line LNCaP was used to study the role of HARP on cancer cell growth, migration, and angiogenic potential in vitro and in vivo.

RESULTS

Exogenous human recombinant HARP was mitogenic for LNCaP cells. By decreasing the expression of endogenous HARP, we found that HARP was essential for LNCaP cell migration, as well as anchorage-dependent and independent growth. Endothelial cell functions in vitro and blood vessel formation in vivo induced by LNCaP cells were also inhibited when HARP expression was diminished.

CONCLUSIONS

HARP seems to act as an important regulator of diverse biological activities in human prostate cancer cells.

Brain (T(brain)), intra-aorta (T(aorta)), latissimus dorsi muscle (T(m)) and rectal temperature (T(r)) were measured in harp (Pagophilus groenlandicus) and hooded (Cystophora cristata) seals during experimental dives in 4 degrees C water. The median brain cooling was about 1 degrees C during 15 min diving, but in some cases it was as much as 2.5 degrees C. Cooling rates were slow for the first couple of minutes, but increased significantly after about 5 min of diving. The onset of cooling sometimes occurred before the start of the dive, confirming that the cooling is under cortical control, like the rest of the diving responses. T(aorta) also fell significantly, and was always lower than T(brain), while T(m) was fairly stable during dives. Detailed studies of the vascular anatomy of front flippers revealed that brachial arterial blood can be routed either through flipper skin capillaries for nutritive purposes and return through sophisticated vascular heat exchangers to avoid heat loss to the environment, or, alternatively, through numerous arterio-venous shunts in the skin and return by way of large superficial veins, which then carry cold blood to the heart. In the latter situation the extent to which the brain is cooled is determined by the ratio of carotid to brachial arterial blood flow, and water temperature, and the cooling is selective in that only those organs that are circulated will be cooled. It is concluded that T(brain) is actively down-regulated during diving, sometimes by as much as 2.5 degrees C, whereby cerebral oxygen requirements may be reduced by as much as 25% during extended dives.

OBJECTIVE

To introduce a method to correct phase errors (e.g., from B0 inhomogeneity) in tagging images, which may affect harmonic phase (HARP) evaluation.

METHODS

The phase images corresponding to the negative and positive harmonic peaks in k-space are combined before HARP evaluation to eliminate any spurious phase. To validate in vivo, two complementary spatial modulation of magnetization (CSPAMM) data sets were collected for each volunteer and evaluated with conventional HARP, using either the positive or the negative harmonic peak, and with peak-combination HARP.

RESULTS

Elimination of phase distortion by peak combination was observed in vitro and in vivo. Improved reproducibility of motion parameters was found with peak-combination HARP.

CONCLUSIONS

With peak-combination HARP, reproducibility of contractile parameters is improved, and consequently, the number of subjects needed to detect statistically significant changes in contractile function can be reduced to one third compared to conventional HARP evaluation.

After recent isolations of Brucella sp. from pinnipeds and cetaceans, a survey was initiated to investigate the prevalence of Brucella sp. infections and serologic evidence of exposure in marine mammals stranded along the coasts of Connecticut and Rhode Island. One hundred and nineteen serum samples from four species of cetaceans and four species of pinnipeds were collected from 1985 to 2000 and tested for antibodies to Brucella sp. using the brucellosis card test, buffered acidified plate antigen test, and rivanol test. In addition, 20 of these were necropsied between 1998 and 2000, with lymphoid and visceral tissues cultured for Brucella sp. Three of 21 (14%) harbor seals (Phoca vitulina) and four of 53 (8%) harp seals (Phoca groenlandica) were seropositive. Brucella sp. was isolated from two of four (50%) harbor seals and three of nine (33%) harp seals. Of the five animals with positive cultures, two were seropositive and three seronegative. Brucella sp. was most frequently cultured from the lung and axillary, inguinal, and prescapular lymph nodes. Tissues from which Brucella sp. was isolated showed no gross or histopathologic changes. These results indicate that marine mammals stranded along the coast of southern New England can be exposed to and infected with Brucella sp.

BACKGROUND

Music has been used in the acute clinical care setting as an adjunct to current treatment modalities. Previous studies have indicated that some types of music may benefit patients by reducing pain and anxiety, and may have an effect on physiological measures.

OBJECTIVE

To evaluate the scientific foundation for the implementation of a complementary therapy, harp playing. The research questions for this pilot study were: Does live harp playing have an effect on patient perception of anxiety, pain, and satisfaction? Does live harp playing produce statistically and clinically significant differences in physiological measures of heart rate, systolic and diastolic blood pressure, respiratory rate, and oxygen saturation?

METHODS

A prospective, quasiexperimental, repeated measures design was used with a convenience sampling.

METHODS

Orlando Regional Medical Center, Orlando Fla.

METHODS

Subjects wer eligible for the study if they were postoperative and admitted to a hard-wired-bedside-monitored room of the Vascular Thoracic Unit within the 3 days of the study period.

METHODS

A singl e20-minute live harp playing session.

METHODS

Visual analog scales (VAS) were used to measure patient anxiety and pain. Patient satisfaction was measured with a 4-item questionnaire. Physiological measures (heart rate, systolic and diastolic blood pressure, respiratory rate, and oxygen saturation) were recorded from the bedside monitor.

METHODS

Visual analog scales (VAS) were completed just before harp playing, 20 minutes after harp playing was started, and 10 minutes after completion. Patient satisfaction with the experience was measured with a 4-item questionnaire. Physiological measures (heart rate, systolic and diastolic blood pressure, respiratory rate, and oxygen saturation) were recorded from the bedside monitor at baseline (5 minutes before study setup), at zero, 5, 10, 15, and 20 minutes after harp playing began, and at 5 and 10 minutes after harp playing stopped.

RESULTS

Seventeen patients were used in this study, with a retrospective power of .91. Results indicate that listening to live harp music has a positive effect on patient perception of anxiety (P=.000), pain (P=.000) and satisfaction. Live harp playing also produced statistically significant differences in physiological measures of systolic blood pressure (P=.046), and oxygen saturation (P=.011). Although all values over time trended downward, the changes of other variables were not adequate to achieve statistical or clinical significance.

CONCLUSIONS

Subjects in this study experienced decreased pain and anxiety with the harp intervention, and slight reductions in physiologic variable values. It is not possible in this study to determine if the results were due to the harp music, the presence of the harpist and data collector, or both. Future research is recommended using a control group and comparison of live versus recorded harp music with a wider variety of diagnoses and procedures.

There has been a dramatic increase in the body of evidence demonstrating the benefits that come from health research. In 2014, the funding bodies for higher education in the UK conducted an assessment of research using an approach termed the Research Excellence Framework (REF). As one element of the REF, universities and medical schools in the UK submitted 1,621 case studies claiming to show the impact of their health and other life sciences research conducted over the last 20 years. The recently published results show many case studies were judged positively as providing examples of the wide range and extensive nature of the benefits from such research, including the development of new treatments and screening programmes that resulted in considerable reductions in mortality and morbidity.Analysis of specific case studies yet again illustrates the international dimension of progress in health research; however, as has also long been argued, not all populations fully share the benefits. In recognition of this, in May 2013 the World Health Assembly requested the World Health Organization (WHO) to establish a Global Observatory on Health Research and Development (R&D) as part of a strategic work-plan to promote innovation, build capacity, improve access, and mobilise resources to address diseases that disproportionately affect the world's poorest countries.As editors of Health Research Policy and Systems (HARPS), we are delighted that our journal has been invited to help inform the establishment of the WHO Global Observatory through a Call for Papers covering a range of topics relevant to the Observatory, including topics on which HARPS has published articles over the last few months, such as approaches to assessing research results, measuring expenditure data with a focus on R&D, and landscape analyses of platforms for implementing R&D. Topics related to research capacity building may also be considered. The task of establishing a Global Observatory on Health R&D to achieve the specified objectives will not be easy; nevertheless, this Call for Papers is well timed - it comes just at the point where the evidence of the benefits from health research has been considerably strengthened.

A mathematical model of the Escherichia coli Pho regulon was developed to study the induction of the phoA gene by starvation for inorganic phosphate. The model includes phosphate transport, detection of the phosphate concentration at the cell surface, and the signal transduction cascade ultimately leading to the induction of various Pho-controlled genes. Four parameters were manipulated to match the dynamic response of a culture growing with phosphate as the growth-limiting substrate to available experimental data for alkaline phosphatase production and internal phosphate concentration. Steady-state analysis demonstrates that the cascade design of this genetic control system gives rise to a harp transition between the uninduced and induced state for a small change in the external phosphate concentration. Parameter sensitivity indicates that the dissociation constant of the repression complex (which holds PhoR in the inactive form when phosphate is in excess), the rate constants for PhoB and PhoR phosphorylation, and the rate constant for induced transcription of Pho genes have the most influence over the expression of Pho-controlled genes. Changes in the repression complex dissociation constant and the PhoB/PhoR phosphorylation rates alter the sensitivity of the phosphate-starvation response to external phosphate concentration, whereas changes in the transcription rate constant affect the gain of the system. The model also predicts that additional Pho promoter (i.e., for the production of a heterologous protein from the phoA promoter on a plasmid) titrate activator protein PhoB A, such that a lower phosphate concentration is required to initiate expression from a high-copy plasmid than from a single-copy plasmid or the chromosome.

This review deals only with the evolutionary history of core Arctic marine mammals: polar bear (Ursus maritimus), walrus (Odobenus rosmarus), bearded seal (Erignathus barbatus), harp seal (Pagophilus groenlandica), ringed seal (Phoca hispida), bowhead whale (Balaena mysticetus), white whale (Delphinapterus leucas), and narwhal (Monodon monoceras). Sections on the evolutionary background of pinnipeds and whales help to provide a better perspective on these core species. Polar bears stemmed from brown bears about the Early to Middle Pleistocene. Fossils are rare; the earliest records are from approximately Early Weichselian deposits of Kew Bridge, London, and Svalbard. Existing Pacific and Atlantic walruses probably arose from splitting of a former Holarctic range during a Pleistocene glacial phase of extensive sea ice in the Canadian Arctic. The earliest known bearded seal remains are from Early to Middle Pleistocene deposits of Norfolk, England, and Cape Deceit, Alaska. Other Pleistocene fossils of this species are recorded from the North Sea, southwestern Sweden, and the Champlain Sea that existed in eastern North America approximately 12 000-10000 BP. The harp seal is the commonest pinniped in the Weichselian deposits of the southern North Sea. The earliest recorded fossil is from about 2 million years ago (2 Ma), from Ocean Point, Alaska. The earliest known Pleistocene ringed seal fossils are from last interglacial deposits near Teshekpuk Lake, Alaska, and Thule, Greenland, although an earlier (3 Ma?) specimen from Malaspina, Alaska, has been reported. This species seems to have been relatively abundant along the coasts of Prince of Wales Island, Alaska, during the Last Glacial Maximum. The bowhead whale probably originated in the high latitudes of the Northern Hemisphere. The earliest (mid-Wisconsinan) Canadian remains are from Ellesmere and Devon islands. More than 400 radiocarbon-dated bowhead remains have been used to reconstruct Holocene sea ice history in the Canadian Arctic. White whales are common in the late warming stage (approximately 10 500 BP) of the Champlain Sea and are one of the commonest marine mammal fossils in Late Pleistocene North Sea deposits. Fourteen narwhal specimens of Late Glacial or Early Holocene age are known from Atlantic Canada, as well as Ellesmere, Baffin, and Prince of Wales islands in Arctic Canada. Arctic marine mammals have tended to shift to more southerly ranges during glacial phases of the Pleistocene.

BACKGROUND

Music therapy has been recommended as an adjuvant therapy for both preterm infants and mothers during their stay in the neonatal intensive care unit (NICU), and has been shown to have beneficial effects.

OBJECTIVE

To study the usefulness of combining live harp music therapy and kangaroo care (KC) on short-term physiological and behavioral parameters of preterm infants and their mothers in the NICU setting.

METHODS

Included in this study were stable infants born between 32 and 37 weeks of gestation, with normal hearing. Mother-infant dyads were randomly assigned to KC and live harp music therapy or to KC alone. Using repeated measures, neonatal and maternal heart rate, oxygen saturation and respiratory rate were recorded along with neonatal behavioral state and maternal anxiety state. Maternal age, ethnicity, education, and love of music were documented.

RESULTS

Fifty-two mother-infant dyads were tested. Compared with KC alone, KC and live harp music therapy had a significantly beneficial effect on maternal anxiety score (46.8 +/- 10 vs. 27.7 +/- 7.1, respectively, P < 0.01). Infants' physiological responses and behavior did not differ significantly. No correlation was found between mothers' age, ethnicity, years of education and affinity for music, and anxiety scores (P = 0.2 to 0.5 for all four variables).

CONCLUSIONS

KC combined with live harp music therapy is more beneficial in reducing maternal anxiety than KC alone. This combined therapy had no apparent effect on the tested infants' physiological responses or behavioral state.