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The eastern Australia coastline is characterized by impressive coastal landforms and an extensive northward-moving longshore drift system that have been influenced by a stable, long-term tectonic history over the Quaternary period. However, the timing and drivers of the formation of two conspicuous landscape features—Fraser Island (K’gari) and the Great Barrier Reef—remain poorly understood. Here we use optically stimulated luminescence and palaeomagnetic dating to constrain the formation of the extensive dunes that make up Fraser Island, the world’s largest sand island, and adjacent Cooloola Sand Mass in southeastern Queensland. We find that both formed between 1.2 Ma and 0.7 Ma, during a global climate reconfiguration across the Middle Pleistocene transition. They formed as a direct result of increased amplitude of sea-level fluctuations associated with increasing global ice volume that redistributed previously stored sediment across the continental shelf. The development of Fraser Island dramatically reduced sediment supply to the continental shelf north of the island. This facilitated widespread coral reef formation in the southern and central Great Barrier Reef and was a necessary precondition for its development. This major reorganization of the coastal sedimentary system is probably not unique to eastern Australia and should be investigated in other passive-margin coastlines.

Stream restoration, such as channel reconfiguration and riparian zone revegetation, is increasing in response to aquatic impairment in agroecosystems. Though riparian zones effectively remove nitrogen (N), conditions that foster nitrate (NO3−) removal (e.g., soil saturation, low oxygen, available carbon) may facilitate the release of soluble reactive phosphorus (SRP) and greenhouse gases (GHGs—carbon dioxide [CO2], methane [CH4], and nitrous oxide [N2O]). In this study, water quality and GHG fluxes were quantified seasonally at agricultural restored, unrestored, and forested riparian zones via networks of wells and static chambers. Carbon dioxide comprised the majority of GHG emissions, and CO2 fluxes were lower at the restored site than the forested site (medians: 0.71 g C m−2 day−1 and 1.29 g C m−2 day−1, respectively). The restored site was a net CH4 source (median: 1.20 mg C m−2 day−1), while the other sites were net CH4 sinks (medians: − 1.00 to − 1.76 mg C m−2 day−1). Sites had comparable N2O emissions. Subsurface SRP was lower at the restored than unrestored agricultural sites, while median NO3− removal efficiency was higher (restored: 91%, unrestored: 35–66%). Over time, NO3− removal and CO2 fluxes increased post-restoration. Methane emissions were elevated when the restored riparian zone was a CO2 and N2O sink and NO3− removal was high. Despite variability within and between sites, seasonal conditions (temperature, water table height, precipitation) and site characteristics (geomorphology, soils) remained key explanatory variables for riparian N removal and GHG release. Overall, riparian restoration may promote N removal without increasing total GHG emissions.

Bipolar disorder (BD) is a neuropsychiatric illness defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. Lithium is an effective drug for BD, but 30-40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of "clock genes" and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms. However, circadian rhythms have not been evaluated in BD patient neurons from Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients characterized for lithium responsiveness and matched controls. We identified strong circadian rhythms in Per2-luc expression in NPCs and neurons from controls and Li-R, but NPC rhythms in Li-R had a shorter circadian period. Li-NR rhythms were low amplitude and profoundly weakened. In NPCs and neurons, expression of PER2 was higher in both BD groups compared to controls. In neurons, PER2 protein levels were higher in BD than controls, especially in Li-NR samples. In single cells, NPC and neuron rhythms in both BD groups were desynchronized compared to controls. Lithium lengthened period in Li-R and control neurons but failed to alter rhythms in Li-NR. In contrast, temperature entrainment increased amplitude across all groups, and partly restored rhythms in Li-NR neurons. We conclude that neuronal circadian rhythm abnormalities are present in BD and most pronounced in Li-NR. Rhythm deficits in BD may be partly reversible through stimulation of entrainment pathways.

HighlightsDenitrification enzyme activity (DEA) was measured in stream sediments of restored and unrestored agricultural streams.Nitrate, sediment characteristics, riparian vegetation, and geomorphology influenced DEA.Pools at restored sites had lower organic carbon, coarser sediment textures, and lower denitrification potential.Restoration strategies should increase organic carbon and residence times through complex flowpaths.Abstract. Agricultural land use, channel modifications, and riparian vegetation composition can affect instream denitrification by altering geomorphic features, such as sediment texture, organic matter, retention time, and hyporheic exchange. Stream and riparian restoration is widely implemented in agricultural watersheds to mitigate excess nutrient export to sensitive downstream waters; however, the cumulative impact of channel reconstruction and altered channel and near-stream morphology on nitrogen dynamics remains poorly understood. We measured denitrification enzyme activity (DEA) and environmental variables (e.g., water chemistry, sediment texture, and organic matter) in different geomorphic features in agriculturally influenced streams in North Carolina with varied channel and riparian zone characteristics. Our results indicate that denitrification is primarily influenced by increased transport of nitrate (NO3-) to the streams in wetter months. Secondarily, structural factors, including riparian vegetation and stream geomorphology, impact denitrification by controlling the distribution of sediment texture and organic carbon. In the newly restored stream, we observed coarser streambed sediments and low sediment organic carbon, especially in scour pools constructed downstream from cross-vanes. Lower DEA was observed in restored pools (39.1 ng N g-1 dry mass h-1) compared to naturally occurring pools (70.7 to 278.1 ng N g-1 dry mass h-1). These results highlight the need for restoration strategies to be directed at increasing organic carbon and residence times through complex flowpaths (e.g., meanders, root wads, artificial woody debris dams). Keywords: Denitrification, Freshwater, Nitrogen, Restoration, Riparian, Stream, Water quality.

Riparian zones have been used for water quality management with respect to NO in subsurface flow and total P (TP), sediments, and pesticides in overland flow for decades. Only recently has the fate and transport of soluble reactive P (SRP), Hg, emerging contaminants, and greenhouse gas (GHG) fluxes (NO, CO, and CH) been examined in riparian zones. Overall, riparian zones are efficient at reducing emerging contaminants in subsurface flow and only function as hot spots of methylmercury production in the landscape when dominated by Hg-rich wet organic soils. However, riparian zones do not provide consistent benefits with respect to SRP removal or GHG emissions. Although most existing riparian models almost exclusively focus on NO removal, recent developments in riparian models demonstrate the potential for using easily accessible digital environmental datasets to simulate and scale up riparian functions beyond NO removal to include SRP, TP, and GHG dynamics. To further inform integrated watershed management efforts, more research should be conducted on how various practices, including stream restoration, subsurface drainage, two-stage ditches, beaver dam analogues, denitrification bioreactors and permeable reactive barriers, artificial wetlands, and short-rotation forestry crops affect riparian water and air quality functions. Riparian zone benefits should be discussed not only with respect to water and air quality, but also in terms of recreation, habitat for wildlife, and other ecosystem services. More research is needed to fully address potential water quality or air quality tradeoffs associated with riparian zone management in a multicontaminant-multiuse landscape context.

Although floodplain restoration may improve stream-riparian connectivity and increase channel stability through cross-vane installation, stream bank regrading, and buffer revegetation, the impact of these geomorphic alterations on denitrification across the aquatic-terrestrial interface is poorly understood. Seasonal denitrification enzyme activity (DEA) was compared in stream-riparian ecotones of four streams with varying hydrologic connection, riparian vegetation composition, and agricultural influence. Riparian and stream DEA was generally higher in sites adjacent to agricultural fields due to proximity to nitrate source. Mean DEA was higher in the dormant season (riparian: 928 ± 116 ng N g⁻¹ dry mass [DM] h⁻¹, stream: 108 ± 149 ng N g⁻¹ DM h⁻¹) than in the growing season (riparian: 355 ± 55 ng N g⁻¹ DM h⁻¹, stream: 45 ± 40 ng N g⁻¹ DM h⁻¹) and was influenced by antecedent precipitation, soil texture, and landscape characteristics (land use, vegetation type, topography) in multivariate models. Hot spots of denitrification occurred at the confluence of fine soil textures with high organic matter and moisture, often at low-lying areas of the landscape. At the restored site, we observed enhanced denitrification in the reconnected floodplain but decreased stream denitrification capacity in pools. Across all sites, streams had lower DEA than riparian zones, stressing the importance of restoration approaches designed to conserve riparian areas and maintain hydrologic connectivity. Easily obtainable data including precipitation, adjacent land use, vegetation, and stream and floodplain geomorphology reasonably predicted denitrification potential compared with more complex models, showing potential for application in water resources and nitrogen management.

In mammals, the master circadian clock resides in the suprachiasmatic nucleus (SCN). The SCN is characterized by robust circadian oscillations of clock gene expression and neuronal firing. The synchronization of circadian oscillations among individual cells in the SCN is attributed to intercellular coupling. Previous studies have shown that gap junctions, specifically those composed of connexin-36 (Cx36) subunits, are required for coupling of electrical firing among SCN neurons at a time scale of milliseconds. However, it remains unknown whether Cx36 gap junctions also contribute to coupling of circadian (~24 h) rhythms of clock gene expression. Here, we investigated circadian expression patterns of the clock gene Period 2 (Per2) in the SCN of Cx36-deficient mice using luminometry and single-cell bioluminescence imaging. Surprisingly, we found that synchronization of circadian PER2 expression rhythms is maintained in SCN explants from Cx36-deficient mice. Since Cx36 expression levels change with age, we also tested circadian running-wheel behavior of juvenile (3–4 weeks old) and adult (9–30 weeks old) Cx36-deficient mice. We found that impact of connexin-36 expression on circadian behavior changes greatly during postnatal development. However, consistent with the intact synchrony among SCN cells in cultured explants, Cx36-deficient mice had intact locomotor circadian rhythms, although adults displayed a lengthened period in constant darkness. Our data indicate that even though Cx36 may be required for electrical coupling of SCN cells, it does not affect coupling of molecular clock gene rhythms. Thus, electrical coupling of neurons and coupling of circadian clock gene oscillations can be regulated independently in the SCN.

This essay identifies major lessons related to the 500th anniversary of the Reformation from the perspective of the Secretaries of Christian World Communions. Drawing on the invitation to all Christians "to come with us along the way to a deeper communion" ( From Conflict to Communion , Lutheran-Catholic Theological Commission, 2013), it highlights several key conversations at annual meetings of the Secretaries. They stressed that this commemoration is not just a Roman Catholic and Lutheran event but also an opportunity for an ecumenical celebration of God's gift of unity to the whole church.

Background Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. Methods We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). Results In these SCN-specific Bmal1 -knockdown (SCN- Bmal1 -KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN- Bmal1 -KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN- Bmal1 -KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Conclusions Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN- Bmal1 -KD mice as a new animal model of depression.

Bipolar disorder (BD) is characterized by depression, mania, and circadian rhythm abnormalities. Lithium, a treatment for BD stabilizes mood and increases circadian rhythm amplitude. However, in fibroblasts grown from BD patients, lithium has weak effects on rhythm amplitude compared to healthy controls. To understand the mechanism by which lithium differentially affects rhythm amplitude in BD cells, we investigated the extracellular-signal-regulated kinase (ERK) and related signaling molecules linked to BD and circadian rhythms. In fibroblasts from BD patients, controls and mice, we assessed the contribution of the ERK pathway to lithium-induced circadian rhythm amplification. Protein analyses revealed low phospho-ERK1/2 (p-ERK) content in fibroblasts from BD patients vs. controls. Pharmacological inhibition of ERK1/2 by PD98059 attenuated the rhythm amplification effect of lithium, while inhibition of two related kinases, c-Jun N-terminal kinase (JNK), and P38 did not. Knockdown of the transcription factors CREB and EGR-1, downstream effectors of ERK1/2, reduced baseline rhythm amplitude, but did not alter rhythm amplification by lithium. In contrast, ELK-1 knockdown amplified rhythms, an effect that was not increased further by the addition of lithium, suggesting this transcription factor may regulate the effect of lithium on amplitude. Augmentation of ERK1/2 signaling through DUSP 6 knockdown sensitized NIH3T3 cells to rhythm amplification by lithium. In BD fibroblasts, DUSP 6 knockdown reversed the BD rhythm phenotype, restoring the ability of lithium to increase amplitude in these cells. We conclude that the inability of lithium to regulate circadian rhythms in BD may reflect reduced ERK activity, and signaling through ELK-1.

Bipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells. We used fluorescent dyes to measure Ca2+ changes in BD and control fibroblasts after lithium treatment, and bioluminescent reporters to measure Per2::luc rhythms in fibroblasts from BD patients, human controls, and mice while pharmacologically or genetically manipulating calcium channels. Longitudinal expression of LTCC genes (CACNA1C, CACNA1D and CACNB3) was then measured over 12–24 h in BD and control cells. Our results indicate that independently of LTCCs, lithium stimulated intracellular Ca2+ less effectively in BD vs. control fibroblasts. In longitudinal studies, pharmacological inhibition of LTCCs or knockdown of CACNA1A, CACNA1C, CACNA1D and CACNB3 altered circadian rhythm amplitude. Diltiazem and knockdown of CACNA1C or CACNA1D eliminated lithium's ability to amplify rhythms. Knockdown of CACNA1A or CACNB3 altered baseline rhythms, but did not affect rhythm amplification by lithium. In human fibroblasts, CACNA1C genotype predicted the amplitude response to lithium, and the expression profiles of CACNA1C, CACNA1D and CACNB3 were altered in BD vs. controls. We conclude that in cells from BD patients, calcium signaling is abnormal, and that LTCCs underlie the failure of lithium to amplify circadian rhythms.

Alcohol use results in changes in intestinal epithelial cell turnover and microbial translocation, yet less is known about the consequences on intestinal lymphocytes in the gut. Here, we compared T-cell subsets in the intestine of macaques before and after 3 months of chronic alcohol administration to examine the effects of alcohol on intestinal T-cell subsets.Rhesus macaques received either alcohol or isocaloric sucrose as a control treatment daily over a 3-month period via indwelling gastric catheters. Intestinal lymphocyte subsets were identified in biopsy samples by flow cytometry. Twenty-four hours prior to sampling, animals were inoculated with bromo-deoxyuridine (BrdU) to assess lymphocyte proliferation. Immunohistochemistry was performed on tissue samples to quantitate CD3+ cells.Animals receiving alcohol had increased rates of intestinal T-cell turnover of both CD4+ and CD8+ T cells as reflected by increased BrdU incorporation. However, absolute numbers of T cells were decreased in intestinal tissues as evidenced by immunohistochemistry for total CD3 expression per mm(2) intestinal lamina propria in tissue sections. Combining immunohistochemistry and flow cytometry data showed that the absolute numbers of CD8+ T cells were significantly decreased, whereas absolute numbers of total CD4+ T cells were minimally decreased.Collectively, these data indicate that alcohol exposure to the small intestine results in marked loss of CD3+ T cells, accompanied by marked increases in CD4+ and CD8+ T-cell proliferation and turnover, which we speculate is an attempt to maintain stable numbers of T cells in tissues. This suggests that alcohol results in accelerated T-cell turnover in the gut, which may contribute to premature T-cell senescence. Further, these data indicate that chronic alcohol administration results in increased levels of HIV target cells (proliferating CD4+ T cells) that may support higher levels of HIV replication in intestinal tissues.

Like neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in the brain, single fibroblasts can function as independent oscillators. In the SCN, synaptic and paracrine signaling among cells creates a robust, synchronized circadian oscillation, whereas there is no evidence for such integration in fibroblast cultures. However, interactions among single-cell fibroblast oscillators cannot be completely excluded, because fibroblasts were not isolated in previous work. In this study, we tested the autonomy of fibroblasts as single-cell circadian oscillators in high- and low-density culture, by single-cell imaging of cells from PER2::LUC circadian reporter mice. We found greatly reduced PER2::LUC rhythmicity in low-density cultures, which could result from lack of either constitutive or rhythmic paracrine signals from neighboring fibroblasts. To discriminate between these 2 possibilities, we mixed PER2::LUC wild-type (WT) cells with nonluminescent, nonrhythmic Bmal1–/– cells, so that density of rhythmic cells was low but overall cell density remained high. In this condition, WT cells showed clear rhythmicity similar to high-density cultures. We also mixed PER2::LUC WT cells with nonluminescent, long period Cry2–/– cells. In this condition, WT cells showed a period no different from cells cultured with rhythmic WT cells or nonrhythmic Bmal1–/– cells. In previous work, we found that low K+ suppresses fibroblast rhythmicity, and we and others have found that either low K+ or low Ca2+ suppresses SCN rhythmicity. Therefore, we attempted to rescue rhythmicity of low-density fibroblasts with high K+ (21 mM), high Ca2+ (3.6 mM), or conditioned medium. Conditioned medium from high-density fibroblast cultures rescued rhythmicity of low-density cultures, whereas high K+ or Ca2+ medium did not consistently rescue rhythmicity. These data suggest that fibroblasts require paracrine signals from adjacent cells for normal expression of rhythmicity, but that these signals do not have to be rhythmic, and that rhythmic signals from other cells do not affect the intrinsic periods of fibroblasts.

Light is the primary signal that calibrates circadian neural circuits and thus coordinates daily physiological and behavioral rhythms with solar entrainment cues. Drosophila and mammalian circadian circuits consist of diverse populations of cellular oscillators that exhibit a wide range of dynamic light responses, periods, phases, and degrees of synchrony. How heterogeneous circadian circuits can generate robust physiological rhythms while remaining flexible enough to respond to synchronizing stimuli has long remained enigmatic. Cryptochrome is a short-wavelength photoreceptor that is endogenously expressed in approximately half of Drosophila circadian neurons. In a previous study, physiological light response was measured using real-time bioluminescence recordings in Drosophila whole-brain explants, which remain intrinsically light-sensitive. Here we apply analysis of real-time bioluminescence experimental data to show detailed dynamic ensemble representations of whole circadian circuit light entrainment at single neuron resolution. Organotypic whole-brain explants were either maintained in constant darkness (DD) for 6 days or exposed to a phase-advancing light pulse on the second day. We find that stronger circadian oscillators support robust overall circuit rhythmicity in DD, whereas weaker oscillators can be pushed toward transient desynchrony and damped amplitude to facilitate a new state of phase-shifted network synchrony. Additionally, we use mathematical modeling to examine how a network composed of distinct oscillator types can give rise to complex dynamic signatures in DD conditions and in response to simulated light pulses. Simulations suggest that complementary coupling mechanisms and a combination of strong and weak oscillators may enable a robust yet flexible circadian network that promotes both synchrony and entrainment. A more complete understanding of how the properties of oscillators and their signaling mechanisms facilitate their distinct roles in light entrainment may allow us to direct and augment the circadian system to speed recovery from jet lag, shift work, and seasonal affective disorder.

Bipolar disorder (BD) and major depressive disorder (MDD) are heritable neuropsychiatric disorders associated with disrupted circadian rhythms. The hypothesis that circadian clock dysfunction plays a causal role in these disorders has endured for decades but has been difficult to test and remains controversial. In the meantime, the discovery of clock genes and cellular clocks has revolutionized our understanding of circadian timing. Cellular circadian clocks are located in the suprachiasmatic nucleus (SCN), the brain’s primary circadian pacemaker, but also throughout the brain and peripheral tissues. In BD and MDD patients, defects have been found in SCN-dependent rhythms of body temperature and melatonin release. However, these are imperfect and indirect indicators of SCN function. Moreover, the SCN may not be particularly relevant to mood regulation, whereas the lateral habenula, ventral tegmentum, and hippocampus, which also contain cellular clocks, have established roles in this regard. Dysfunction in these non-SCN clocks could contribute directly to the pathophysiology of BD/MDD. We hypothesize that circadian clock dysfunction in non-SCN clocks is a trait marker of mood disorders, encoded by pathological genetic variants. Because network features of the SCN render it uniquely resistant to perturbation, previous studies of SCN outputs in mood disorders patients may have failed to detect genetic defects affecting non-SCN clocks, which include not only mood-regulating neurons in the brain but also peripheral cells accessible in human subjects. Therefore, reporters of rhythmic clock gene expression in cells from patients or mouse models could provide a direct assay of the molecular gears of the clock, in cellular clocks that are likely to be more representative than the SCN of mood-regulating neurons in patients. This approach, informed by the new insights and tools of modern chronobiology, will allow a more definitive test of the role of cellular circadian clocks in mood disorders.

In this article, we attempt to formulate an integrated view of the necessity of human interdependence from the disciplines of theology, philosophy, and psychology. First, we discuss the social personalist model of the Trinity so as to understand the utility of relatedness from a theological perspective. Next, we review the philosophical concept of phenomenology in order to make sense of the relationship between humans and the world in which they interact and live. Finally, we explicate the psychoanalytic concept of intersubjectivity so as to offer Christian therapists a relational heuristic for working with Christian clients in psychotherapy. Overall, we suggest that drawing from these three disciplines can better elucidate the lifelong, legitimate need that humans have for intimate connection with, and nurturance from, one another in order to ameliorate the shame attached to the necessity of human interdependence in Western societies that commonly promote increased individualism and autonomy.

The suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes circadian rhythms of cells and tissues throughout the body. In SCN neurons, rhythms of clock gene expression are suppressed by manipulations that hyperpolarize the plasma membrane or lower intracellular Ca(2+). However, whether clocks in other cells also depend on membrane potential and calcium is unknown. In this study, the authors investigate the effects of membrane potential and intracellular calcium on circadian rhythms in mouse primary fibroblasts. Rhythms of clock gene expression were monitored using a PER2::LUC knockin reporter. Rhythms were lost or delayed at lower (hyperpolarizing) K(+) concentrations. Bioluminescence imaging revealed that this loss of rhythmicity in cultures was due to loss of rhythmicity of single cells rather than loss of synchrony among cells. In lower Ca(2+) concentrations, rhythms were advanced or had shorter periods. Buffering intracellular Ca(2+) by the calcium chelator 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) or manipulation of inositol triphosphate (IP(3))-sensitive intracellular calcium stores by thapsigargin delayed rhythms. These results suggest that the circadian clock in fibroblasts, as in SCN neurons, is regulated by membrane potential and Ca(2+). Changes in intracellular Ca(2+) may mediate the effects of membrane potential observed in this study.

In this article, we present a psychodynamic explanation for the complex crime of filicide motivated by religious delusions. To begin, we provide an overview of filicide, including its typology and epidemiology. Second, we examine the psychoanalytic theories of Heinz Kohut and Otto Kernberg so as to better understand how family-of-origin experiences add to the ways in which psychotic disorders later take shape in filicide cases. Third, we offer an explication of the psychology of religion, including the role that religious defences and religious delusions play in cases involving filicide. Ultimately, we hypothesise that mothers with religious delusions commit acts of filicide due to the dynamic and reciprocal interaction between mental illness, psychological functioning, and the psychological role played by religion. We conclude our article with a case illustration to demonstrate our theoretical model.

Cells in the suprachiasmatic nucleus (SCN) display remarkable precision, while either physically or chemically decoupling these cells from each other leads to a dramatic increase in period-to-period variability. Where previous studies have classified cells as either arrhythmic or circadian, our wavelet analysis reveals that individual cells, when removed from network interactions, intermittently express circadian and/or longer infradian periods. We reproduce the characteristic period distribution of uncoupled SCN cells with a stochastic model of the uncoupled SCN cell near a bifurcation in Bmal1 transcription repression. This suggests that the uncoupled cells may be switching between 2 oscillatory mechanisms: the indirect negative feedback of protein complex PER-CRY on the expression of Per and Cry genes, and the negative feedback of CLOCK-BMAL1 on the expression of the Bmal1 gene. The model is particularly sensitive near this bifurcation point, with only a small change in Bmal1 transcription repression needed to switch from the stable precision of coupled SCN cells to the unstable oscillations of decoupled individual cells, making this rate constant, an ideal target for cell signaling in the SCN.

Because we can observe oscillation within individual cells and in the tissue as a whole, the suprachiasmatic nucleus (SCN) presents a unique system in the mammalian brain for the analysis of individual cells and the networks of which they are a part. While dispersed cells of the SCN sustain circadian oscillations in isolation, they are unstable oscillators that require network interactions for robust cycling. Using cluster analysis to assess bioluminescence in acute brain slices from PERIOD2::Luciferase (PER2::LUC) knockin mice, and immunochemistry of SCN from animals harvested at various circadian times, we assessed the spatiotemporal activation patterns of PER2 to explore the emergence of a coherent oscillation at the tissue level. The results indicate that circadian oscillation is characterized by a stable daily cycle of PER2 expression involving orderly serial activation of specific SCN subregions, followed by a silent interval, with substantial symmetry between the left and right side of the SCN. The biological significance of the clusters identified in living slices was confirmed by co-expression of LUC and PER2 in fixed, immunochemically stained brain sections, with the spatiotemporal pattern of LUC expression resembling that revealed in the cluster analysis of bioluminescent slices. We conclude that the precise timing of PER2 expression within individual neurons is dependent on their location within the nucleus, and that small groups of neurons within the SCN give rise to distinctive and identifiable subregions. We propose that serial activation of these subregions is the basis of robustness and resilience of the daily rhythm of the SCN.

Background: We have previously compared outcome in two groups of systemic sclerosis (SSc) patients with disease onset a decade apart and we reported data on 5 year survival and cumulative incidence of organ disease in a contemporary SSc cohort. The present study examines longer term outcome in an additional cohort of SSc followed for 10 years.Methods: We have examined patients with disease onset between years 1995 and 1999 allowing for at least 10 years of follow-up in a group that has characteristics representative for the patients we see in contemporary clinical practice.Results: Of the 398 patients included in the study, 252 (63.3%) had limited cutaneous (lc) SSc and 146 (36.7%) had diffuse cutaneous (dc) SSc. The proportion of male patients was higher among the dcSSc group (17.1% v 9.9%, p = 0.037) while the mean age of onset was significantly higher among lcSSc patients (50 ± 13 v 46 ± 13 years ± SD, p = 0.003).During a 10 year follow-up from disease onset, 45% of the dcSSc and 21% of the lcSSc subjects developed clinically significant pulmonary fibrosis, p < 0.001. Among them approximately half reached the endpoint within the first 3 years (23% of dcSSc and 10% of lcSSc) and over three quarters within the first 5 years (34% and 16% respectively). There was a similar incidence of pulmonary hypertension (PH) in the two subsets with a steady rate of increase over time. At 10 years 13% of dcSSc and 15% of lcSSc subjects had developed PH (p=0.558), with the earliest cases observed within the first 2 years of disease. Comparison between subjects who developed PH in the first and second 5 years from disease onset demonstrated no difference in demographic or clinical characteristics, but 5-year survival from PH onset was better among those who developed this complication later in their disease (49% v 24%), with a strong trend towards statistical significance (p = 0.058). Incidence of SSc renal crisis (SRC) was significantly higher among the dcSSc patients (12% v 4% in lcSSc, p = 0.002). As previously observed, the rate of development of SRC was highest in the first 3 years of disease- 10% in dcSSc and 3% in lcSSc. All incidences of clinically important cardiac disease developed in the first 5 years from disease onset (7% in dcSSc v 1% in lcSSc, p < 0.001) and remained unchanged at 10 years. As expected, 10-year survival among lcSSc subjects was significantly higher (81%) compared to that of dcSSc patients (70%, p = 0.006). Interestingly, although over the first 5 years the death rate was much higher in the dcSSc cohort (16% v 6% in lcSSc), over the following years it became very similar for both subsets (14% and 13% between years 5 and 10, and 18% and 17% between years 10 and 15 for dcSSc and lcSSc respectively).Conclusions: Even though dcSSc patients have higher incidence for most organ complications compared to lcSSc subjects, the worse survival among them is mainly due to higher early mortality rate. Mortality rate after first 5 years of disease becomes comparable in the two disease subsets.Disclosure statement: The authors have declared no conflicts of interest.

Recent reports indicate that hypoxia influences the circadian clock through the transcriptional activities of hypoxia-inducible factors (HIFs) at clock genes. Unexpectedly, we uncover a profound disruption of the circadian clock and diurnal transcriptome when hypoxic cells are permitted to acidify to recapitulate the tumor microenvironment. Buffering against acidification or inhibiting lactic acid production fully rescues circadian oscillation. Acidification of several human and murine cell lines, as well as primary murine T cells, suppresses mechanistic target of rapamycin complex 1 (mTORC1) signaling, a key regulator of translation in response to metabolic status. We find that acid drives peripheral redistribution of normally perinuclear lysosomes away from perinuclear RHEB, thereby inhibiting the activity of lysosome-bound mTOR. Restoring mTORC1 signaling and the translation it governs rescues clock oscillation. Our findings thus reveal a model in which acid produced during the cellular metabolic response to hypoxia suppresses the circadian clock through diminished translation of clock constituents.

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in the mammalian brain, responsible for coordinating circadian (ca 24 h) rhythms throughout the body. When individual SCN neurons are dispersed in low density culture, they generate independent circadian oscillations in neuronal firing rate. This observation has led to the widely accepted conclusion that single SCN neurons are autonomous circadian oscillators. More recent studies using bioluminescence imaging to monitor rhythms of clock gene expression have indicated that fibroblasts, too, are autonomous circadian oscillators. But does this mean that the fibroblast should “replace the SCN as the in vitro model of choice”? On the contrary, the SCN is much more than a population of independent cellular oscillators. SCN function depends on important network interactions that allow for cell synchrony, enhanced pacemaker precision, reinforcement of rhythm amplitude, and robustness against genetic perturbations. The distribution of phases of cells within the SCN network also permits variously phased rhythmic output signals, as well as the encoding of seasonal changes in photoperiod and other features of environmental lighting history. Thus, unlike fibroblasts, SCN neurons are designed to be “team players,” and SCN network interactions are integral to the normal function of the SCN as a circadian pacemaker.

This study was designed to investigate the use and impact of a continuous glucose monitoring system (the FreeStyle Navigator) under home-use conditions in the self-management of type 1 diabetes.A 20 day masked phase, when real-time data and alarms were not available, was compared with a subsequent 40 day unmasked phase for a number of specified measures of glycaemic variability. HbA(1c) (measured by DCA 2000) and a hypoglycaemia fear survey were recorded at the start and end of the study.The study included 48 patients with type 1 diabetes (mean age 35.7 +/- 10.9, range 18-61 years; diabetes duration 17.0 +/- 9.5 years). Two patients did not complete the study for personal reasons. Comparing masked (all 20 days) and unmasked (last 20 days) phases, the following reductions were seen: time outside euglycaemia from 11.0 to 9.5 h/day (p = 0.002); glucose SD from 3.5 to 3.2 mmol/l (p0.001); hyperglycaemic time (10.0 mmol/l) from 10.3 to 8.9 h/day (p = 0.0035); mean amplitude of glycaemic excursions (peak to nadir) down by 10% (p0.001); high blood glucose index down by 18% (p = 0.0014); and glycaemic risk assessment diabetes equation score down by 12% (p = 0.0013). Hypoglycaemic time (3.9 mmol/l) decreased from 0.70 to 0.64 h/day without statistical significance (p0.05). Mean HbA(1c) fell from 7.6 +/- 1.1% at baseline to 7.1 +/- 1.1% (p0.001). In the hypoglycaemia fear survey, the patients tended to take less snacks at night-time after wearing the sensor.Home use of a continuous glucose monitoring system has a positive effect on the self-management of diabetes. Thus, continuous glucose monitoring may be a useful tool to decrease glycaemic variability.

Self-renunciation or self-denial, although often misunderstood, is a foundational concept in several major religions and is frequently associated with spiritual maturity. In spite of this, the action of self-renunciation has been viewed with suspicion by the psychological community and criticized as repressive. This article argues that the concept of self-denial found in the Sufi tradition of rebirth and the salvation paradox found in the synoptic Gospels can bring a valuable perspective to psychotherapy. First, a brief summary of the history of psychotherapy and its contributions to the understanding of the self are provided. Next, a cursory overview of the Sufi tradition of rebirth is given. Third, the salvation paradox found in the synoptic Gospels is reviewed. It is argued that these two traditions offer valuable insight into ideas surrounding the self. Finally, the clinical implications of self-denial are discussed, and conclusions are drawn related to how psychotherapy can benefit self-renunciation.

INTRODUCTION: Mental health professionals are gatekeepers of patient confidentiality. Yet, confidentiality held too strictly, by allowing a potentially dangerous driver to assume control of a car, endangers society. Recent court cases have mandated that mental health professionals must warn those who may be potentially harmed by patients. In spite of this, disagreements linger as to whether it is the responsibility of governmental agencies or mental health professionals to decide who is unfit to operate a vehicle because of cognitive impairment. Methods: This article addresses the legally relevant considerations when working with cognitively compromised individuals who operate a motor vehicle. Legal issues surrounding confidentiality, patient rights, foreseeable risk, and the duty to warn and protect are presented in order to understand their relationship to recent court rulings. IMPACT ON INDUSTRY: The impact on the mental health care industry includes not only concerns about increased insurance premiums or costs due to alleged negligence or litigation expenses secondary to failure to ensure the safety of an impaired client under their care. Mental health care providers are aware that the welfare of clients with impairment to cognitive decision making ability may require unique considerations for safety such as ensuring safe and appropriate transportation. Language: en

Two major approaches have been used to model circadian clocks. Qualitative modeling, used prior to the recent wealth of detailed molecular knowledge, makes general predictions but cannot provide detailed mechanistic insights. The more recent biophysical approach, on the other hand, incorporates the biochemical events that drive the clock and can make detailed and testable molecular predictions. These predictions are being tested using new experimental techniques that measure reaction kinetics and the behavior of individual cells. A joint modeling and experimental approach has recently been used to understand how mutations affecting phosphorylation can lead to a short circadian period in tau mutant hamsters and in humans with familial advanced sleep phase syndrome (FASPS). Another recent study has revealed novel single-cell phenotypes of clock gene mutations, demanding revision of current biophysical models yet validating certain model predictions that were previously overlooked. A new paradigm for clock research is emerging in which modeling inspires new experimental efforts, experimental data inspire new modeling efforts, and joint modeling/experimental studies lead to a deeper understanding of mammalian circadian rhythms.

The Substance Abuse and Mental Illness (SAMI) program combines cognitive rehabilitation and dual-diagnosis substance abuse treatment within a stages of change context. This article describes the development, implementation, and preliminary outcome analysis of the SAMI program in a forensic hospital.

Questions: Does the addition of cyclic pneumatic soft-tissue compression during the 6-week immobilisation period following fracture of the distal radius result in a faster recovery of muscle strength and joint range of motion? Does it result in a larger recovery of muscle strength and joint range of motion immediately after the immobilisation period (at 6 weeks) or four weeks after the immobilisation period (at 10 weeks)? Design: Randomised controlled trial with concealed allocation and assessor blinding. Participants: 21 patients with fracture of the distal radius. Intervention: The experimental group received cyclic pneumatic soft-tissue compression during the 6-week immobilisation period whereas the control group received usual care. Both groups were instructed to actively make a fist 100 times per day during the 6-week immobilisation period and were given an exercise program during the 4-week post-immobilisation period. Outcome measures: Function was measured as power grip, pinch grip, key grip, and supination strength using dynamometry from Week 1 to 10 as well as wrist flexion/extension and forearm supination/pronation range of motion using goniometry from Week 6 to 10. The outcome measures are presented as a percentage of the intact side. Results: The experimental group improved significantly faster than the control group in muscle strength from Week 1 to 10 (p ≤ 0.001) but not in joint range of motion from Week 6 to 10 (p > 0.05). By Week 6, the experimental group was 12–26% stronger and had 8–14% more range of motion than the control group. By Week 10, the experimental group was 24–29% stronger and had 10–15% more range of motion than the control group. Conclusion: The findings indicate that a larger clinical trial is warranted and should incorporate direct measures of fracture healing. [Challis MJ, Jull GJ, Stanton WR, Welsh MK (2007) Cyclic pneumatic soft-tissue compression enhances recovery following fracture of the distal radius: a randomised controlled trial. Australian Journal of Physiotherapy 53: 247–252]

Stalking encompasses a wide range of behavioral patterns, risk factors, interpersonal dynamics, and dangerousness. To account for these diverse phenomena, we propose that stalking behavior is best conceptualized by a dynamic interaction of attachment styles and psychodynamic phenomena. This paper articulates a model that explains stalking behavior within the framework of attachment theory. Four prototypical configurations of stalkers and their victims are developed. Each configuration is discussed in terms of a pattern of internal representations, affective constellations, combinations of aggression and narcissism, and potential for future violence. The four configurations proposed here are maintained through stalkers' over ideational linkage fantasies and projective identifications, which range from shame-prone and needy idealization to malevolent torment of the victim. Our model arrays erotomanic, jealous, and persecutory attachments along a continuum of increasingly paranoid and pathological identifications. We argue that these prototypical attachment configurations provide a theoretically driven means of differentiating phases of stalking, and as such provide useful leads in the empirical study and clinical assessment, treatment, and management of stalkers.