Cumulative Prevalence of Confirmed Maltreatment and Foster Care Placement for US Children by Race/Ethnicity, 2011-2016.

Objectives. To estimate the cumulative prevalence of confirmed child maltreatment and foster care placement for US children and changes in prevalence between 2011 and 2016.Methods. We used synthetic cohort life tables and data from the Adoption and Foster Care Analysis and Reporting System and the National Child Abuse and Neglect Data System and population counts from the Centers for Disease Control and Prevention.Results. US children's cumulative prevalence of confirmed maltreatment remained stable between 2011 and 2016 at about 11.7% (95% confidence interval [CI] = 11.6%, 11.7%) of the population and increased by roughly 11% for foster care placement from 4.8% (95% CI = 4.8%, 4.8%) to 5.3% (95% CI = 5.3%, 5.4%). American Indian/Alaska Native children experienced the largest change, an 18.0% increase in confirmed maltreatment risk from 13.4% (95% CI = 13.1%, 13.6%) to 15.8% (95% CI = 15.6%, 16.1%) and a 21% increase in foster care placement risk from 9.4% (95% CI = 9.2%, 9.6%) to 11.4% (95% CI = 11.2%, 11.6%).Conclusions. Confirmed child maltreatment and foster care placement continued to be experienced at high rates in the United States in 2012 through 2016, with especially high risks for American Indian/Alaska Native children. Rates of foster care have increased, whereas rates of confirmed maltreatment have remained stable.

The Cumulative Prevalence of Termination of Parental Rights for U.S. Children, 2000-2016.

Recent research has used synthetic cohort life tables to show that having a Child Protective Services investigation, experiencing confirmed maltreatment, and being placed in foster care are more common for American children than would be expected based on daily or annual rates for these events. In this article, we extend this literature by using synthetic cohort life tables and data from the Adoption and Foster Care Analysis and Reporting System to generate the first cumulative prevalence estimates of termination of parental rights. The results provide support for four conclusions. First, according to the 2016 estimate, 1 in 100 U.S. children will experience the termination of parental rights by age 18. Second, the risk of experiencing this event is highest in the first few years of life. Third, risks are highest for Native American and African American children. Nearly 3.0% of Native American children and around 1.5% of African American children will ever experience this event. Finally, there is dramatic variation across states in the risk of experiencing this event and in racial/ethnic inequality in this risk. Taken together, these findings suggest that parental rights termination, which involves the permanent loss of access to children for parents, is far more common than often thought.

Spreading vasodilatation in the murine microcirculation: attenuation by oxidative stress-induced change in electromechanical coupling.

Regulation of blood flow in microcirculatory networks depends on spread of local vasodilatation to encompass upstream arteries; a process mediated by endothelial conduction of hyperpolarization. Given that endothelial coupling is reduced in hypertension, we used hypertensive Cx40ko mice, in which endothelial coupling is attenuated, to investigate the contribution of the renin-angiotensin system and reduced endothelial cell coupling to conducted vasodilatation of cremaster arterioles in vivo. When the endothelium was disrupted by light dye treatment, conducted vasodilatation, following ionophoresis of acetylcholine, was abolished beyond the site of endothelial damage. In the absence of Cx40, sparse immunohistochemical staining was found for Cx37 in the endothelium, and endothelial, myoendothelial and smooth muscle gap junctions were identified by electron microscopy. Hyperpolarization decayed more rapidly in arterioles from Cx40ko than wild-type mice. This was accompanied by a shift in the threshold potential defining the linear relationship between voltage and diameter, increased T-type calcium channel expression and increased contribution of T-type (3 µmol l(-1) NNC 55-0396), relative to L-type (1 µmol l(-1) nifedipine), channels to vascular tone. The change in electromechanical coupling was reversed by inhibition of the renin-angiotensin system (candesartan, 1.0 mg kg(-1) day(-1) for 2 weeks) or by acute treatment with the superoxide scavenger tempol (1 mmol l(-1)). Candesartan and tempol treatments also significantly improved conducted vasodilatation. We conclude that conducted vasodilatation in Cx40ko mice requires the endothelium, and attenuation results from both a reduction in endothelial coupling and an angiotensin II-induced increase in oxidative stress. We suggest that during cardiovascular disease, the ability of microvascular networks to maintain tissue integrity may be compromised due to oxidative stress-induced changes in electromechanical coupling.

Non-linear relationship between hyperpolarisation and relaxation enables long distance propagation of vasodilatation.

Blood flow is adjusted to tissue demand through rapidly ascending vasodilatations resulting from conduction of hyperpolarisation through vascular gap junctions. We investigated how these dilatations can spread without attenuation if mediated by an electrical signal. Cremaster muscle arterioles were studied in vivo by simultaneously measuring membrane potential and vessel diameter. Focal application of acetylcholine elicited hyperpolarisations which decayed passively with distance from the local site,while dilatation spread upstream without attenuation. Analysis of simultaneous recordings at the local site revealed that hyperpolarisation and dilatation were only linearly related over a restricted voltage range to a threshold potential, beyond which dilatation was maximal. Experimental data could be simulated in a computational model with electrotonic decay of hyperpolarisation but imposition of this threshold. The model was tested by reducing the amplitude of the local hyperpolarisation which led to entry into the linear range closer to the local site and decay of dilatation. Serial section electron microscopy and light dye treatment confirmed that the spread of dilatation occurred through the endothelium and that the two cell layers were tightly coupled. Generality of the mechanism was demonstrated by applying the model to the attenuated propagation of dilatation found in larger arteries.We conclude that long distance spread of locally initiated dilatations is not due to a regenerative electrical phenomenon, but rather a restricted linear relationship between voltage and vessel tone, which minimises the impact of electrotonic decay of voltage. Disease-related alterations in endothelial coupling or ion channel expression could therefore decrease the ability to adjust blood flow to meet metabolic demand.

Depolarization evoked by acetylcholine in mesenteric arteries of hypertensive rats attenuates endothelium-dependent hyperpolarizing factor.

OBJECTIVE: During blockade of endothelium-dependent hyperpolarizing factor (EDHF), acetylcholine evoked larger and faster depolarization in mesenteric arteries of spontaneously hypertensive rats (SHR) than normotensive Wistar-Kyoto (WKY) rats. We studied the mechanism underlying this response and its role in the attenuation of EDHF. METHODS: Electrophysiology, computational modelling and myography were used to study changes in membrane potential and effects on contractility. RESULTS: The large acetylcholine-evoked depolarization in SHR was accompanied by contraction, but this was not seen in WKY rats. The depolarization depended on release of intracellular Ca2+ but was unaffected by nonselective cation channel inhibitors, gadolinium, lanthanum or amiloride. The depolarization was significantly reduced by the Ca2+-dependent Cl- channel inhibitors, niflumic acid or flufenamic acid, or alterations in Cl- gradients using bumetanide (Na/K/Cl transporter inhibitor) or external Cl- replacement with isethionate. These drugs altered the time course of EDHF-evoked hyperpolarizations in SHR, making them indistinguishable from those in WKY rats. EDHF-induced relaxation was less sensitive to acetylcholine in SHR than in WKY rats, but this difference was eliminated following artery pretreatment with bumetanide. Computational modelling in which the SHR fast depolarizing response was selectively modulated mimicked physiologically acquired results obtained in SHR and WKY rats during Cl- -channel blockade. CONCLUSIONS: Acetylcholine evokes a fast depolarization in SHR but not in WKY rats, mediated by the opening of Ca2+-dependent Cl- channels. The depolarization is responsible for a constriction that reduces EDHF-mediated relaxation. Data suggest that Ca2+-dependent Cl- channels may provide a novel therapeutic target for improvement of endothelial dysfunction during hypertension.

Electrical events underlying organized myogenic contractions of the guinea pig stomach.

The stomach generates a characteristic pattern of coordinated activity whereby rings of contraction regularly start in the corpus and migrate slowly down the stomach to the duodenum. This behaviour persists after isolating the stomach and after blocking nervous activity; hence the response is myogenic, resulting from organized contractions of smooth muscle cells lying in the stomach wall. Each ring of contraction is triggered by a long lasting wave of depolarization, termed a slow wave. Slow waves are now known to be generated by sets of interstitial cells of Cajal (ICC), which intermingle with gastric smooth muscle cells. This article describes some studies which identify the roles played by ICC in the on-going generation of coordinated gastric movements. Intramuscular ICC in the corpus generate slow waves and these provide the dominant pacemaker frequency in the stomach. Corporal slow waves, in turn, activate a network of myenteric ICC, which starts in the antrum and slowly conducts waves of depolarization down the stomach. As these waves pass over bundles of circularly orientated muscle cells, they activate a set of intramuscular ICC which lie in the circular muscle layer: these generate slow waves that rapidly spread radially, so triggering each ring of contraction.

An electrical analysis of slow wave propagation in the guinea-pig gastric antrum.

This paper provides an electrical description of the propagation of slow waves and pacemaker potentials in the guinea-pig gastric antrum in anal and circumferential directions. As electrical conduction between laterally adjacent circular muscle bundles is regularly interrupted, anal conduction of pacemaker potentials was assumed to occur via an electrically interconnected chain of myenteric interstitial cells of Cajal (ICC(MY)). ICC(MY) were also connected resistively to serially connected compartments of longitudinal muscle. Circumferential conduction occurred in a circular smooth muscle bundle that was represented as a chain of electrically connected isopotential compartments: each compartment contained a proportion of intramuscular interstitial cells of Cajal (ICC(IM)) that are responsible for the regenerative component of the slow wave. The circular muscle layer, which contains ICC(IM), and the ICC(MY) network incorporated a mechanism, modelled as a two-stage chemical reaction, which produces an intracellular messenger. The first stage of the reaction is proposed to be activated in a voltage-dependent manner as described by Hodgkin and Huxley; the messenger altered the mean rate of discharge of depolarizing unitary potentials as a function of the concentration of messenger according to a conventional dose-effect relationship. A separate membrane conductance, scaled by the product of an independent voltage-sensitive reaction, was included in the ICC(MY) compartments; this was used to describe the primary component of pacemaker potentials and simulated a delay before the activation of this membrane current. The model generates pacemaker potentials and slow waves with propagation velocities similar to those determined in the physiological experiments described in the accompanying paper.

Propagation of slow waves in the guinea-pig gastric antrum.

Intracellular recordings were made from the circular layer of the intact muscular wall of the guinea-pig gastric antrum in preparations where much of the corpus remained attached. When two electrodes were positioned parallel to and near to the greater curvature, slow waves were first detected at the oral site and subsequently at the anal site: the oro-anal conduction velocity was found to be 2.5 mm s(-1). When one electrode was positioned near the greater curvature and the other at a circumferential location, slow waves were first detected near the greater curvature and subsequently at the circumferential site: the circumferential conduction velocity was 13.9 mm s(-1). When recordings were made from preparations in which the circular muscle layer had been removed, the oro-anal and the circumferential conduction velocities were both about 3.5 mm s(-1). When slow waves were recorded from preparations in which much of the myenteric network of antral interstitial cells (ICC(MY)) had been dissected away, slow waves were first detected near the region of intact ICC(MY) and subsequently at a circumferential location: the circumferential conduction velocity of slow waves in regions devoid of ICC(MY) was 14.7 mm s(-1). When the electrical properties of isolated single bundles of circular muscle were determined, their length constants were about 3 mm and their time constant about 230 ms, giving an asymptotic electrotonic propagation velocity of 25 mm s(-1). Oro-anal electrical coupling between adjacent bundles of circular muscle was found to vary widely: some bundles were well connected to neighbouring bundles whereas others were not. Together the observations suggest that the slow oro-anal progression of slow waves results from a slow conduction velocity of pacemaker potentials in the myenteric network of interstitial cells. The rapid circumferential conduction of slow waves results from the electrical properties of the circular muscle layer which allow intramuscular ICC (ICC(IM)) to support the radial spread of slow waves: regions of high resistance between bundles prevent the anally directed spread of slow waves within the circular layer.

Atypical slow waves generated in gastric corpus provide dominant pacemaker activity in guinea pig stomach.

When intracellular recordings were made from the circular layer of the intact muscular wall of the isolated guinea pig gastric corpus, an ongoing regular high frequency discharge of slow waves was detected even though this region lacked myenteric interstitial cells. When slow waves were recorded from preparations consisting of both the antrum and the corpus, slow waves of identical frequency, but with different shapes, were generated in the two regions. Corporal slow waves could be distinguished from antral slow waves by their time courses and amplitudes. Corporal slow waves, like antral slow waves, were abolished by buffering the internal concentration of calcium ions, [Ca2+]i, to low levels, or by caffeine, 2-aminoethoxydiphenyl borate or the chloride channel blocker DIDS. Corporal preparations demonstrated an ongoing discharge of unitary potentials, as has been found in all other tissues containing interstitial cells. The experiments show that the corpus provides the dominant pacemaker activity which entrains activity in other regions of the stomach and it is suggested that this activity is generated by corporal intramuscular interstitial cells.

Role of interstitial cells of Cajal in the control of gastric motility.

Most regions of the gastrointestinal tract generate spontaneous electrical and mechanical activity in the absence of stimulation. When electrical recordings are made from slow muscle cells lying in the gastrointestinal tract, a regular discharge of long lasting waves of depolarization, slow waves, is detected. It has recently become apparent that slow waves are generated by a specialized population of smooth muscle cells, known as interstitial cells of Cajal (ICC). ICC can be subdivided into at least two separate groups. In most regions of the gastrointestinal tract, one group of ICC form a network that generates pacemaker potentials, so producing rhythmical membrane potential changes in the adjacent muscle layers. The second group of ICC are distributed amongst the smooth muscle cells and are tightly electrically coupled to them. In some regions of the gut, the second group of ICC augment the waves of pacemaker depolarization, so ensuring that voltage-dependent calcium channels in the smooth muscles are activated during each slow wave cycle. In addition, the second group of ICC are densely innervated by inhibitory and excitatory nerve terminals. Thus intrinsic nerve terminals, rather than communicating directly with smooth muscle cells, selectively innervate ICC and release transmitters directly onto them. The signals that are generated in the ICC, by the neurally released transmitters, then alter the activity of surrounding smooth muscle cells.

Properties of unitary potentials recorded from myenteric interstitial cells of Cajal distributed in the guinea-pig gastric antrum.

Intracellular recordings were made from myenteric interstitial cells of Cajal (ICC-MY) distributed in the guinea-pig gastric antrum to investigate the properties of unitary potentials. In most cells studied, pacemaker potentials with initial fast transient and following plateau components were generated periodically, and intervals between the potentials were quiescent. However, there were few cells (less than 5% of cells examined) which showed discharge of unitary potentials spontaneously in the intervals between pacemaker potentials. The amplitude and frequency of unitary potentials appeared to be random variables, as observed in isolated circular smooth muscle bundles of the guinea-pig gastric antrum. BAPTA-AM (an intracellular Ca2+ chelator) or papaverine (a non-selective phosphodiesterase inhibitor) reduced the discharge frequency of unitary potentials, with associated decrease in the frequency of pacemaker potentials. These agents finally abolished both unitary potentials and pacemaker potentials. In preparations showing no detectable generation of unitary potentials, depolarization of the membrane with high-K solution ([K+]o = 10.6 mM) elicited generation of unitary potentials during intervals between pacemaker potentials. Pinacidil (an opener of K(ATP)-channels) hyperpolarized the membrane and increased the frequency and amplitude of unitary potentials with no alteration to the relationship between the amplitudes of unitary potentials and their half-widths. These results suggest that the elevation of intracellular Ca2+ concentration is causally related to the generation of unitary potentials in pacemaker cells. They are consistent with the proposition that the depolarization produced by a burst of unitary potentials triggers the primary component of pacemaker potentials in ICC-MY, which induces a release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive internal stores and then activates Ca2+-sensitive Cl- -channels to form the plateau component. Similarities and differences in unitary potentials between circular muscle and pacemaker cells are discussed.