Depressive symptoms and HIV among a cohort of adolescent young men and transgender women who have sex with men, Bangkok and Nakhon Sawan, Thailand, 2017-2019.

Screening for depression may identify persons for HIV prevention services and to ensure linkage to care for ART and mental health. We assessed factors associated with depressive symptoms using multiple logistic regression among 15- to 29-year-old gay, bisexual or other men who have sex with men (MSM) and transgender women who have sex with men (TGW) attending HIV prevention clinics at Silom Community Clinic or Bangrak Hospital in Bangkok or Rainbow Clinic in Nakhon Sawan, Thailand. We defined depressive symptoms as a self-report of feelings of sadness that impacted daily life in the past one month. Among 192 MSM, 51 TGW, and 11 gender-questioning persons screened: 12.6% met the criteria for depression; 5.9% had new HIV diagnosis. Independently associated factors which increase the risk of depressive symptoms included: studying in a private school (AOR 7.17); experiencing any type of bullying (AOR 2.8); having a partner with HIV (AOR 4.1); and learning about the study from sources other than a friend (AOR 4.2). Given many youths had depressive symptoms, screening for depression and connection to mental health services would be beneficial in sexual health settings to meet the needs of HIV-vulnerable youth.

Changes in genetic risk for emotional eating across the menstrual cycle: a longitudinal study.

BACKGROUND: Previous studies have shown significant within-person changes in binge eating and emotional eating across the menstrual cycle, with substantial increases in both phenotypes during post-ovulation. Increases in both estradiol and progesterone levels appear to account for these changes in phenotypic risk, possibly via increases in genetic effects. However, to date, no study has examined changes in genetic risk for binge phenotypes (or any other phenotype) across the menstrual cycle. The goal of the present study was to examine within-person changes in genetic risk for emotional eating scores across the menstrual cycle. METHOD: Participants were 230 female twin pairs (460 twins) from the Michigan State University Twin Registry who completed daily measures of emotional eating for 45 consecutive days. Menstrual cycle phase was coded based on dates of menstrual bleeding and daily ovarian hormone levels. RESULTS: Findings revealed important shifts in genetic and environmental influences, where estimates of genetic influences were two times higher in post- as compared with pre-ovulation. Surprisingly, pre-ovulation was marked by a predominance of environmental influences, including shared environmental effects which have not been previously detected for binge eating phenotypes in adulthood. CONCLUSIONS: Our study was the first to examine within-person shifts in genetic and environmental influences on a behavioral phenotype across the menstrual cycle. Results highlight a potentially critical role for these shifts in risk for emotional eating across the menstrual cycle and underscore the need for additional, large-scale studies to identify the genetic and environmental factors contributing to menstrual cycle effects.

Effect of laundry activities on in-stream concentrations of linear alkylbenzene sulfonate in a small rural South African river.

In many parts of the world clothes are washed near to or in rivers and streams. Little information is available on resulting concentrations of detergent ingredients or on any potential effects caused. In this study, the fate of a commonly used anionic surfactant, linear alkylbenzene sulphonate (LAS) was investigated in a reach of the Balfour River (Eastern Cape Province, South Africa) which was regularly used as a site for laundry activity. Samples of river water were collected upstream of the main washing site and at a number of locations downstream on several occasions in winter and summer. Sediment samples were also collected and analysed. In addition, a household survey was conducted to ascertain the amount of detergent used and the distribution of washing practices. The results of the survey suggested that the use of riverside locations for laundry activities was seasonal. Most washing tended to be done at home during the winter with riverside sites used more frequently during the summer months. The monitoring data showed that LAS concentrations in water were very variable. They were occasionally high in the immediate vicinity of the laundry site (up to 342 microg L(-1)) but were generally very low (<11 microg L(-1)) at downstream monitoring stations, suggesting that LAS was rapidly dissipated by a combination of degradation, hydrodynamic dispersion and dilution. Concentrations in the immediate vicinity of the washing site were lower than expected on the basis of the household survey because most waste water was disposed of on the river bank rather than directly in the river. No ecological effects are expected from LAS emissions at this site.

Multielectrode impedance tuning: reducing noise and improving stimulation efficacy.

Multielectrode arrays (MEAs) have emerged as a leading technology for extracellular, electrophysiological investigations of neuronal networks. The study of biological neural networks is a difficult task that is further confounded by mismatches in electrode impedance. Electrode impedance plays an important role in shaping incoming signals, determining thermal noise, and influencing the efficacy of stimulation. Our approach to optimally reduce thermal noise and improving the reliability of stimulation is twofold minimize the impedance and match it across all electrodes. To this aim, we have fabricated a device that allows for the automated, impedance-controlled electroplating of micro-electrodes. This device is capable of rapidly (minutes) producing uniformly low impedances across all electrodes in an MEA. The need for uniformly low impedances is important for controlled studies of neuronal networks; this need will increase in the future as MEA technology scales from tens of electrodes to thousands.

Agitation in Alzheimer's disease is a manifestation of frontal lobe dysfunction.

OBJECTIVES: (1) To investigate the prevalence and characteristics of agitation in patients with Alzheimer's disease (AD) and other forms of dementia; (2) to explore the association between agitation and other clinical variables, including disease severity, functional impairment and other neuropsychiatric symptoms, and (3) to determine the predictors of agitation. METHODS: Data for 427 men and women with dementia from outpatient clinics of the University of California, Los Angeles Alzheimer's Disease Center were analyzed. There were 277 patients with AD, 43 with vascular dementia, 47 with mixed dementia, 45 with frontotemporal dementia and 15 with dementia with Lewy bodies. Patients were evaluated with the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Functional Activities Questionnaire (FAQ), neuropsychological tests and the Caregiver Appraisal instrument. SPSS10 was utilized for statistical analysis. RESULTS: There was no difference in agitation subscale scores among patients with dementia of various etiologies. In patients with AD, there was increased prevalence of agitation with increasing dementia severity. Agitation contributed substantially to caregiver burden and impact. There was a significant correlation between the FAQ and the NPI agitation subscale score after adjusting for MMSE scores. Delusion, disinhibition and irritability subscale scores in AD patients were correlated with agitation across disease severity. Subscale scores of frontally mediated behaviors including irritability, delusions and disinhibition predicted most of the variance in agitation levels. CONCLUSION: Agitation is common in AD and other dementias and has a marked impact on caregivers. It is related to dementia severity and to specific types of associated psychopathology implicating frontal lobe dysfunction. The present study is the largest and most comprehensive assessment of agitation reported. The data suggest that agitation in AD is a frontal lobe syndrome. Frontal lobe dysfunction may predispose AD patients to agitation by exaggerating behavioral responses to many types of coexisting psychopathology or environmental provocations.

Anaerobic benzene oxidation coupled to nitrate reduction in pure culture by two strains of Dechloromonas.

Benzene contamination is a significant problem. It is used in a wide range of manufacturing processes and is a primary component of petroleum-based fuels. Benzene is a hydrocarbon that is soluble, mobile, toxic and stable, especially in ground and surface waters. It is poorly biodegraded in the absence of oxygen. However, anaerobic benzene biodegradation has been documented under various conditions. Although benzene biomineralization has been demonstrated with nitrate, Fe(III), sulphate or CO2 as alternative electron acceptors, these studies were based on sediments or microbial enrichments. Until now there were no organisms in pure culture that degraded benzene anaerobically. Here we report two Dechloromonas strains, RCB and JJ, that can completely mineralize various mono-aromatic compounds including benzene to CO2 in the absence of O2 with nitrate as the electron acceptor. This is the first example, to our knowledge, of an organism of any type that can oxidize benzene anaerobically, and we demonstrate the potential applicability of these organisms to the treatment of contaminated environments.

Survival and neurite outgrowth of rat cortical neurons in three-dimensional agarose and collagen gel matrices.

To better understand interactions between neurons and extracellular matrix equivalents, embryonic day-18 rat cortical neurons were immobilized and maintained in culture for up to 24 days in agarose and type I collagen gels. Using live/dead staining, neuronal cultures in low density collagen gel lasted at least 3 weeks. At 14 days, over 50% of immobilized cells in collagen gel were found viable while in low density agarose gel no cells survived. In situ cell death detection showed that most, if not all, dead cells in either of the gels underwent apoptosis. The collagen-trapped neurons exhibited normal neuronal polarity and developed long neurites, estimated at over 500 microm. The results suggest that collagen, because it is a major extracellular matrix constituent, suppresses apoptosis and provides a suitable substrate for neuronal survival and differentiation.

Cognitive and metabolic responses to metrifonate therapy in Alzheimer disease.

OBJECTIVE: The objective of this study was to identify the relation between the cognitive benefit seen with the cholinesterase inhibitor metrifonate and changes in brain metabolism as visualized with [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). BACKGROUND: The regional metabolic correlates of treatment with cholinesterase inhibitors are poorly understood. METHODS: Six patients with mild to moderate Alzheimer disease (AD) were evaluated before and after treatment with the long-lasting cholinesterase inhibitor metrifonate. Patients were given 60 or 80 mg of metrifonate per day (based on weight) for 6 to 12 weeks. Clinical evaluations included the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory. Imaging was carried out using FDG-PET. The PET studies, registered to a probabilistic anatomic atlas, were normalized across the group's mean intensity levels and subjected to voxel-by-voxel subtraction of the posttreatment minus pretreatment studies. Subvolume thresholding corrected random lobar noise to produce a three-dimensional functional significance map. RESULTS: The criteria for cognitive improvement with treatment were met for the MMSE (>2 points improvement from baseline), and the drawing subscale of the ADAS-cog was significantly improved with treatment. The three-dimensional significance map revealed a significant metabolic increase of the dorsolateral frontoparietal network on the left and bilateral temporal cortex with metrifonate treatment. CONCLUSION: The clinical benefits observed in AD with cholinesterase inhibitor therapy are associated with a metabolic increase of heteromodal cognitive and medial temporal networks.

Primary neural precursor cell expansion, differentiation and cytosolic Ca(2+) response in three-dimensional collagen gel.

To investigate the ability to culture neural precursor cells in a three-dimensional (3D) collagen gel, neuroepithelial cells were isolated from embryonic day 13 rat cortex, dispersed within type I collagen and maintained for up to 30 days in vitro. Cultured in Neuorobasal medium supplemented with B27 containing basic fibroblast growth factor, the collagen-entrapped precursor cells actively expanded and formed clone-like clusters. Many cells in the center of the cluster were proliferating as revealed by 5-bromo-2'-deoxyuridine uptake. Some cells began to migrate away from the center at 5 days and were labeled by either neuronal marker neuron-specific beta-tubulin (TuJ1) or astrocytic marker glial fibrillary acidic protein. The differentiated neurons (TuJ1(+)) exhibited characteristic cytosolic Ca(2+) oscillations in response to excitatory neurotransmitter glutamate. These findings suggest the suitability of the 3D culture system for the proliferation and differentiation of neural precursor cells.

Orbital and dorsolateral frontal perfusion defect associated with behavioral response to cholinesterase inhibitor therapy in Alzheimer's disease.

The authors retrospectively explored the behavioral and functional imaging profile of Alzheimer's disease (AD) patients who respond to cholinesterase inhibitor therapy by using the Neuropsychiatric Inventory (NPI) and baseline [99mTc]HMPAO SPECT. Thirty AD patients were divided into three groups (Responders, Nonresponders, and Unchanged) based on their behavioral response to donepezil. Responders had significantly (P < or = 0.01) more pretreatment irritability, disinhibition (P < or = 0.05), and euphoria (P = 0.05) than Nonresponders and significantly lower lateral orbital frontal (P < 0.00001) and dorsolateral frontal (P < or = 0.0005) perfusion bilaterally. A pretreatment orbitofrontal syndrome may predict behavioral response to cholinesterase inhibitor therapy in AD.

Immobilization of neural cells in three-dimensional matrices for biosensor applications.

To overcome logistical difficulties with current designs of cell- or tissue-based biosensors which have individual cells or tissue slices immobilized on membranes or microelectrode arrays, we have proposed a system that uses three-dimensional cultures of neural cells immobilized in hydrogel matrices. In this design, immobilized cells would be maintained in a reservoir and then transferred to a detector platform when needed for analysis. The development of such a system relies upon a renewable supply of cells and the ability to culture cells for long periods of time in three-dimensions while maintaining their physiological function. To investigate the ability to culture neural cells in 3D matrices, embryonic rat cortical neurons and astrocytes were immobilized by matrix entrapment in a novel sugar poly(acrylate) hydrogel and collagen gels. The sugar poly(acrylate) hydrogel does not appear to support neural cell growth as a result of a lack of cell adherence, small pore size and, possibly, harshness of synthesis conditions. In contrast, collagen gels support the growth of cortical neurons, astrocytes, as well as neural progenitor cells. Evidence is also presented from immunocytochemistry and patch-clamp measurements which shows that neural progenitor cells proliferate in culture and can be induced to differentiate into neural cell types. Thus, they potentially represent a renewable cell source.

Sustained release of silver from periodontal wafers for treatment of periodontitis.

Periodontal wafers intended to treat the underlying infections in patients with periodontitis have been developed. The wafers consist of poly(lactic-co-glycolic acid) as a primary bioerodible polymeric component, poly(ethylene glycol) as a plasticizer and encapsulation aid, and silver nitrate as the antimicrobial agent. The wafers are capable of sustained in vitro release of bioactive silver for at least 4 weeks. The wafers exhibit silver release that follows erosion kinetics, confirming a bulk erosion/release mechanism. In clinical evaluation, sustained release of silver at bactericidal levels for at least 21 days is observed. Staining of hard and soft tissues due to the released silver is minimal and reversible.

Adsorption of plasma proteins on to poly(ethylene oxide)/poly(propylene oxide) triblock copolymer films: a focus on fibrinogen.

Triblock copolymers of the form PEO(alpha)PPO(beta)PEO(alpha) [where PEO is poly(ethylene oxide) and PPO is poly(propylene oxide)] have many biomedical applications, many of which depend on the surface properties of the copolymers and the influence that those properties have on the adsorption of proteins. As a tool to help us better understand, predict and exploit the influence of these triblock copolymers on protein adsorption, we developed a model system in which well-defined monolayers of the copolymers are supported by solid, hydrophobic, microscopic beads. At the bead/water interface, the copolymers all form stable films in which the nominal molecular areas correspond to those of the molecules when they are packed rather tightly at the air/water interface. Beads coated with condensed films of copolymers that contain short PEO segments and elicit appreciable inflammation absorb appreciable quantities of plasma proteins, including fibrinogen, from aqueous solution. Beads coated with fibrinogen aggregate when they are stirred in the presence of thrombin, a consequence of interbead fibrin formation. Beads coated with condensed films of copolymers that contain long PEO segments and elicit little inflammation absorb little plasma protein, and they do not aggregate in the presence of thrombin. Our data and observations are consistent with the prevailing notion that the utility of triblock copolymers as agents for modifying the surface properties of blood-contacting surfaces derives from the influence of the copolymers on the adsorption of plasma proteins. In this regard, the ability of the copolymers to influence fibrinogen-mediated adhesive events may be particularly important. As to the mechanism of protein resistance, our data support the proposal that sibling PEO segments of copolymers in condensed films fold back across their parental PPO cores, limiting access of proteins to the hydrophobic cores themselves.

Ubiquity and diversity of dissimilatory (per)chlorate-reducing bacteria.

Environmental contamination with compounds containing oxyanions of chlorine, such as perchlorate or chlorate [(per)chlorate] or chlorine dioxide, has been a constantly growing problem over the last 100 years. Although the fact that microbes reduce these compounds has been recognized for more than 50 years, only six organisms which can obtain energy for growth by this metabolic process have been described. As part of a study to investigate the diversity and ubiquity of microorganisms involved in the microbial reduction of (per)chlorate, we enumerated the (per)chlorate-reducing bacteria (ClRB) in very diverse environments, including pristine and hydrocarbon-contaminated soils, aquatic sediments, paper mill waste sludges, and farm animal waste lagoons. In all of the environments tested, the acetate-oxidizing ClRB represented a significant population, whose size ranged from 2.31 x 10(3) to 2.4 x 10(6) cells per g of sample. In addition, we isolated 13 ClRB from these environments. All of these organisms could grow anaerobically by coupling complete oxidation of acetate to reduction of (per)chlorate. Chloride was the sole end product of this reductive metabolism. All of the isolates could also use oxygen as a sole electron acceptor, and most, but not all, could use nitrate. The alternative electron donors included simple volatile fatty acids, such as propionate, butyrate, or valerate, as well as simple organic acids, such as lactate or pyruvate. Oxidized-minus-reduced difference spectra of washed whole-cell suspensions of the isolates had absorbance maxima close to 425, 525, and 550 nm, which are characteristic of type c cytochromes. In addition, washed cell suspensions of all of the ClRB isolates could dismutate chlorite, an intermediate in the reductive metabolism of (per)chlorate, into chloride and molecular oxygen. Chlorite dismutation was a result of the activity of a single enzyme which in pure form had a specific activity of approximately 1,928 micromol of chlorite per mg of protein per min. Analyses of the 16S ribosomal DNA sequences of the organisms indicated that they all belonged to the alpha, beta, or gamma subclass of the Proteobacteria. Several were closely related to members of previously described genera that are not recognized for the ability to reduce (per)chlorate, such as the genera Pseudomonas and Azospirllum. However, many were not closely related to any previously described organism and represented new genera within the Proteobacteria. The results of this study significantly increase the limited number of microbial isolates that are known to be capable of dissimilatory (per)chlorate reduction and demonstrate the hitherto unrecognized phylogenetic diversity and ubiquity of the microorganisms that exhibit this type of metabolism.

The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease.

BACKGROUND: Behavioral abnormalities are common in Alzheimer disease (AD); cholinergic treatment reduces the behavioral disturbances of some patients with AD. Characterizing the pretreatment profile of patients who are likely to respond to cholinergic therapy will aid the efficient use of clinical resources. OBJECTIVE: To determine the baseline behavioral profile for 86 patients with AD treated with the cholinesterase inhibitor donepezil hydrochloride. METHODS: Open-label retrospective study of treatment-related behavioral assessments. Based on previous double-blind placebo-controlled experience using the Neuropsychiatric Inventory (NPI), patients were divided into responder (> or =4-point total NPI score decrease, indicating improvement), unchanged (+/-3-point total NPI score change), or nonresponder (> or =4-point total NPI score increase, indicating worsening) groups. The Mini-Mental State Examination assessed cognitive response. RESULTS: Behavioral improvement was seen in 35 patients (41%), worsening in 24 (28%), and no change in 27 (31%). Comparison of profiles in behavioral responders vs nonresponders revealed significantly worse delusions (P = .04), agitation (P = .04), depression (P = .006), anxiety (P = .02), apathy (P = .003), disinhibition (P = .02), and irritability (P<.001) at baseline in responders. Five behaviors changed significantly from baseline, improving for the responders and worsening for the nonresponders: delusions (P = .003 for nonresponders, P = .004 for responders), agitation (P = .01), anxiety (P = .006 for nonresponders, P = .004 for responders), disinhibition (P = .02 for nonresponders, P = .05 for responders), and irritability (P = .003 for nonresponders, P = .001 for responders). The behavioral changes were dose dependent. Cognition did not change significantly with donepezil treatment within any group. CONCLUSIONS: Donepezil has psychotropic properties, and pretreatment behaviors help predict patients' responses to treatment.

Compliance and functional residual capacity after staple versus combined staple/holmium laser lung volume reduction surgery in a rabbit emphysema model.

BACKGROUND: There is some evidence to suggest that laser exposure, when added to standard staple reduction techniques, may result in improved physiologic response to lung volume reduction surgery (LVRS). In this study, we compared physiologic responses of staple LVRS with combined staple/laser in a rabbit emphysema model. METHODS: Ninety-three New Zealand White rabbits underwent emphysema induction with aerosolized elastase 4 weeks before surgery and were killed 1 week after surgery. Treatment groups were bilateral moderate volume staple LVRS (< or =3 g, n = 39), combined moderate volume staple (< or =3 g)/holmium laser LVRS (n = 18), large-volume staple LVRS (> or =3 g, n = 27), or sham surgery (n = 9). RESULTS: Decrease in postoperative static respiratory system compliance by combined moderate-volume staple/laser treatment (1.22 cc/cm H2O) was similar to large-volume staple resection (1.40 cc/cm H2O, p = 0.39), and superior to moderate staple resection (0.82 cc/cm H2O, p = 0.01) or sham surgery (0.09 cc/cm H2O, p = 0.0001). Functional residual capacity decrease was greater after combined moderate staple/laser resection (6.46 cc) than large-volume staple resection (4.52 cc, p = 0.33), moderate-volume staple resection (4.59 cc, p = 0.43), or sham surgery (4.10 cc, p = 0.29). Perioperative mortality was highest after laser/staple LVRS (22%, 4/18). CONCLUSIONS: In this rabbit model, combined staple/ holmium laser reduction for emphysema results in significant improvement in compliance and trends toward improvement in functional residual capacity above staple reduction alone, but with higher mortality.

Anatomical loops and their electrical dynamics in relation to whisking by rat.

An accumulation of anatomical, behavioral, and electrophysiological evidence allows us to identify the neuronal circuitry that is involved with vibrissa-mediated sensation and the control of rhythmic vibrissa movement. Anatomical evidence points to a multiplicity of closed sensorimotor loops, while electrophysiological data delineate the flow of electrical signals in these pathways. These loops process sensory input from the vibrissae and send projections to direct vibrissa movement, starting at the level of the hindbrain and proceeding toward loops that involve multiple structures in the forebrain. The nature of the vibrissa-related electrical signals in behaving animals has been studied extensively at the level of neocortical loops. Two types of spike signal are observed that serve as a reference of vibrissa motion: a fast signal that correlates with the relative phase of the vibrissae within a whisk cycle and a slow signal that correlates with the amplitude, and possibly the set-point, of the vibrissae during a whisk. Both signals are observed in vibrissa primary sensory (S1) cortex, and in some cases they are sufficiently robust to allow vibrissa position to be accurately estimated from the spike train of a single neuron. Unlike the case for S1 cortex, only the slow signal has been observed in vibrissa primary motor (M1) cortex. The control capabilities of M1 cortex were estimated from experiments with anesthetized animals in which progressive areas along the vibrissa motor branch were microstimulated with rhythmically applied currents. The motion of the vibrissae followed stimulation of M1 cortex only for rates that were well below the frequency of rhythmic whisking; in contrast, the vibrissae followed stimulation of the facial nucleus, whose cells directly drive the vibrissae, for rates above that of whisking. In toto, the evidence implies that there is fast signaling from the facial nucleus, through the mystacial pad and the vibrissae and up through sensory cortex, but only slow signaling at the level of the motor cortex and down through the superior colliculus to the facial nucleus. The transformation from fast sensory signals to slow motor control is an unresolved issue. On the other hand, there is a candidate scheme to understand how the fast reference of vibrissa motion in the whisk cycle may be used to decode the angle of the vibrissae upon their contact with an object. We discuss a circuit in which servo mechanisms are used to determine the angle of contact relative to the preferred phase of the fast reference signals. Support for this scheme comes from results with anesthetized animals on the frequency and phase entrainment of intrinsic neuronal oscillators in S1 cortex. A prediction based on this scheme is that the output from a decoder circuit is maximal when the angle of contact differs from the preferred phase of a fast regerence signal. In contrast, for correlation-based schemes the output is maximal when the angle of contact equals the preferred phase.

Circumstances around weapon injury in Cambodia after departure of a peacekeeping force: prospective cohort study.

OBJECTIVE: To examine the circumstances surrounding weapon injury and combatant status of those injured by weapons. DESIGN: Prospective cohort study. SETTING: Northwestern Cambodia after departure of United Nations peacekeeping force. SUBJECTS: 863 people admitted to hospital for weapon injuries over 12 months. MAIN OUTCOME MEASURES: Annual incidence of weapon injury by time period; proportions of injuries inflicted as a result of interfactional combat (combat injuries) and outside such combat (non-combat injuries) by combatant status and weapon type. RESULTS: The annual incidence of weapon injuries was higher than the rate observed before the peacekeeping operation. 30% of weapon injuries occurred in contexts other than interfactional combat. Most commonly these were firearm injuries inflicted intentionally on civilians. Civilians accounted for 71% of those with non-combat injuries, 42% of those with combat related injuries, and 51% of those with weapon injuries of either type. CONCLUSIONS: The incidence of weapon injuries remained high when the disarmament component of a peacekeeping operation achieved only limited success. Furthermore, injuries occurring outside the context of interfactional combat accounted for a substantial proportion of all weapon injuries, were experienced disproportionately by civilians, and were most likely to entail the intentional use of a firearm against a civilian.