Reducing Voltage Hysteresis in Li-Rich Sulfide Cathodes by Incorporation of Mn.

Conventional intercalation-based cathode materials in Li-ion batteries are based on charge compensation of the redox-active cation and can only intercalate one mole of electron per formula unit. Anion redox, which employs the anion sublattice to compensate charge, is a promising way to achieve multielectron cathode materials. Most anion redox materials still face the problems of slow kinetics and large voltage hysteresis. One potential solution to reduce voltage hysteresis is to increase the covalency of the metal-ligand bonds. By substituting Mn into the electrochemically inert Li1.33Ti0.67S2 (Li2TiS3), anion redox can be activated in the Li1.33-2y/3Ti0.67-y/3Mn y S2 (y = 0-0.5) series. Not only do we observe substantial anion redox, but the voltage hysteresis is significantly reduced, and the rate capability is dramatically enhanced. The y = 0.3 phase exhibits excellent rate and cycling performance, maintaining 90% of the C/10 capacity at 1C, which indicates fast kinetics for anion redox. X-ray absorption spectroscopy (XAS) shows that both the cation and anion redox processes contribute to the charge compensation. We attribute the drop in hysteresis and increase in rate performance to the increased covalency between the metal and the anion. Electrochemical signatures suggest the anion redox mechanism resembles holes on the anion, but the S K-edge XAS data confirm persulfide formation. The mechanism of anion redox shows that forming persulfides can be a low hysteresis, high rate capability mechanism enabled by the appropriate metal-ligand covalency. This work provides insights into how to design cathode materials with anion redox to achieve fast kinetics and low voltage hysteresis.

A multicenter study of DDAVP versus platelet transfusions for antiplatelet agent reversal in patients with traumatic brain injury.

BACKGROUND: Antiplatelet agents have been shown to worsen outcomes following traumatic injury. Research on desmopressin (DDAVP) and platelet transfusion for antiplatelet reversal is limited. We aimed to evaluate the effect of these agents on patients taking pre-injury antiplatelet medications who experienced traumatic brain injury (TBI) after blunt trauma. METHODS: This is a retrospective cohort study of adult trauma patients from 2014 to 2021 on aspirin and/or a P2Y12 inhibitor. Patients were stratified into groups based on if they received DDAVP, platelets, both agents, or neither. RESULTS: Of 5525 included patients, 4696 (85.4%) were not reversed, 461 (8.4%) received platelets, 173 (3.1%) received DDAVP, and 172 (3.1%) received both reversals. There was no statistically significant difference in length of stay between, but patients who received platelets or both reversals were more likely to have hospital complications (p < 0.05), longer hospital length of stay (p < 0.001), and longer ICU length of stay (p < 0.001) compared to those who did not receive reversal. A subgroup analysis of patients with a head AIS of 4 or 5 confirmed these findings. CONCLUSIONS: Patients who received platelets or both reversals had a longer length of hospital stay and length of ICU stay. It is difficult to recommend one treatment over another based on our results alone. Further studies are needed to help clarify the risks and benefits of reversal agents in this patient population.

Four-factor prothrombin complex concentrate versus andexanet alfa for the reversal of traumatic brain injuries.

BACKGROUND: Andexanet alfa was approved in 2018 for reversal of direct oral anticoagulants but due to issues of cost and access, four-factor prothrombin complex concentrate (4F-PCC) continues to be used for this indication. The objective of this study is to evaluate outcomes of reversal with these agents in patients with isolated traumatic brain injuries (TBI). METHODS: This is a retrospective review of 35 trauma centres from 2014 to 2021. Patients were included with an Abbreviated Injury Scale (AIS)>2 for head and having received andexanet alfa or 4F-PCC within 24 hours of admission. Patients were excluded if P2Y12 inhibitor use or AIS>2 outside of head. Primary outcome includes rate of mortality/hospice at hospital discharge. Secondary outcomes include a composite of serious hospital complications. A subgroup analysis of severe TBI patients (AIS head 4 or 5) was completed. Multivariable logistic regression was used to account for differences in comorbidities and TBI severity. RESULTS: 4F-PCC was given to 265 patients with another 59 receiving andexanet alfa. Patients in the andexanet alfa group were more likely to have an AIS head score of 5 (47.5% vs 26.1%; p<0.005). After adjusting for severity of TBI and comorbidities with regard to tomortality/hospice, there were 15 (25.4%) patients in the andexanet alfa group and 49 (18.5%) in the 4F-PCC group (OR 1.34; 95% CI 0.67 to 2.71). This remained consistent when looking at severe patients with TBI with 12 (28.6%) andexanet alfa patients and 37 (28.7%) 4F-PCC patients (OR 0.93 (95% CI 0.40 to 2.16)). Severe hospital complications were also similar between groups with 5 (8.5%) andexanet alfa patients as compared with 21 (7.9%) 4F-PCC patients (OR 1.01; 95% CI 0.36 to 2.88). CONCLUSION: There was no firm conclusion on the treatment effect in mortality/hospice or serious complications among isolated TBI patients reversed with 4F-PCC as compared with andexanet alfa.

Genetic and Epigenetic Regulation in Lingo-1: Effects on Cognitive Function and White Matter Microstructure in a Case-Control Study for Schizophrenia.

Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3'-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016-1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology.

Aqueous Cold Sintering of Li-Based Compounds.

Aqueous cold sintering of two lithium-based compounds, the electrolyte Li6.25La3Zr2Al0.25O12 (LLZAO) and cathode material LiCoO2 (LCO), is reported. For LLZAO, a relative density of ∼87% was achieved, whereas LCO was sintered to ∼95% with 20 wt % LLZAO as a flux/binder. As-cold sintered LLZAO exhibited a low total conductivity (10-8 S/cm) attributed to an insulating grain boundary blocking layer of Li2CO3. The blocking layer was reduced with a post-annealing process or, more effectively, by replacing deionized water with 5 M LiCl during cold sintering to achieve a total conductivity of ∼3 × 10-5 S/cm (similar to the bulk conductivity). For LCO-LLZAO composites, scanning electron microscopy and X-ray computer tomography indicated a continuous LCO matrix with the LLZAO phase evenly distributed but isolated throughout the ceramics. [001] texturing during cold sintering resulted in an order of magnitude difference in electronic conductivity between directions perpendicular and parallel to the c-axis at room temperature. The electronic conductivity (∼10-2 S/cm) of cold sintered LCO-LLZAO ceramics at room temperature was comparable to that of single crystals and higher than those synthesized via either conventional sintering or hot pressing.

Vapor Sorption and Halogen-Bond-Induced Solid-Form Rearrangement of a Porous Pharmaceutical.

A porous, nonsolvated polymorph of the voltage-gated sodium channel blocker mexiletine hydrochloride absorbs iodine vapor to give a pharmaceutical cocrystal incorporating an I2Cl- anion that forms a halogen-π interaction with the mexiletine cations. The most thermodynamically stable form of the compound does not absorb iodine. This example shows that vapor sorption is a potentially useful and underused tool for bringing about changes in pharmaceutical solid form as part of a solid form screening protocol.

Designer Gelators for the Crystallization of a Salt Active Pharmaceutical Ingredient-Mexiletine Hydrochloride.

We report an approach to obtain drug-mimetic supramolecular gelators, which are capable of stabilizing metastable polymorphs of the pharmaceutical salt mexiletine hydrochloride, a highly polymorphic antiarrhythmic drug. Solution-phase screening led to the discovery of two new solvated solid forms of mexiletine, a type C 1,2,4-trichlorobenzene tetarto-solvate and a type D nitrobenzene solvate. Various metastable forms were crystallized within the gels under conditions which would not have been possible in solution. Despite typically crystallizing concomitantly with form 1, a pure sample of form 3 was crystallized within a gel of ethyl methyl ketone. Various type A channel solvates were crystallized from gels of toluene and ethyl acetate, in which the contents of the channels varied from those of solution-phase forms. Most strikingly, the high-temperature-stable form 2 was crystallized from a gel in 1,2-dibromoethane: the only known route to access this form at room temperature. These results exemplify the powerful stabilizing effect of drug-mimetic supramolecular gels, which can be exploited in pharmaceutical polymorph screens to access highly metastable or difficult-to-nucleate solid forms.

Impact of Repeated Exposure and Cleaning on Protective Properties of Structural Firefighting Turnout Gear.

The US fire service has become acutely aware of the need to clean PPE after fires. However, there is concern that damage from repeated cleaning may impact critical protection from fireground risk. Using a protocol that included repeated simulated fireground exposures (between 0 and 40 cycles) and/or repeated cleaning with techniques common in the fire service, we found that several important protective properties of NFPA 1971 compliant turnout gear are significantly changed. Outer shell and thermal liner tear strength showed a statistically significant reduction when laundered as compared to wet or dry decontamination. Larger changes in outer shell tear strength resulted when the coat closure incorporated hook & dee clasps as compared with garments using zippered closures. Total Heat Loss (THL) was reduced for all samples that underwent any form of cleaning while Thermal Protective Performance (TPP) was only increased in the gear that was laundered. These results suggest that some important protective properties of bunker gear can be decreased after repeated exposure/cleaning cycles relative to their levels when tested in a new condition. For the specific materials tested, outer shell trap tear strength in the fill direction and seam strength dropped below NFPA 1971 requirements after 40 laundering cycles. The findings for this study may have utility for setting preconditions for the measurement of certain performance properties in future editions of NFPA 1971.

Impact of a Pharmacist-Led Intensive Care Unit Sleep Improvement Protocol on Sleep Duration and Quality.

BACKGROUND: Sleep improvement protocols are recommended for use in the intensive care unit (ICU) despite questions regarding which interventions to include, whether sleep quality or duration will improve, and the role of pharmacists in their development and implementation. OBJECTIVE: To characterize the impact of a pharmacist-led, ICU sleep improvement protocol on sleep duration and quality as evaluated by a commercially available activity tracker and patient perception. METHODS: Critical care pharmacists from a 40-bed, mixed ICU at a large community hospital led the development and implementation of an interprofessional sleep improvement protocol. It included daily pharmacist medication review to reduce use of medications known to disrupt sleep or increase delirium and guideline-based recommendations on both environmental and nonpharmacological sleep-focused interventions. Sleep duration and quality were compared before (December 2018 to December 2019) and after (January to June 2019) protocol implementation in non-mechanically ventilated adults using both objective (total nocturnal sleep time [TST] measured by an activity tracker (Fitbit Charge 2) and subjective (patient-perceived sleep quality using the Richards-Campbell Sleep Questionnaire [RCSQ]) measures. RESULTS: Groups before (n = 48) and after (n = 29) sleep protocol implementation were well matched. After protocol implementation, patients had a longer TST (389 ± 123 vs 310 ± 147 minutes; P = 0.02) and better RCSQ-perceived sleep quality (63 ± 18 vs 42 ± 24 mm; P = 0.0003) compared with before implementation. CONCLUSION AND RELEVANCE: A sleep protocol that incorporated novel elements led to objective and subjective improvements in ICU sleep duration and quality. Application of this study may result in increased utilization of sleep protocols and pharmacist involvement.

Effect of Alteplase Administration on International Normalized Ratio in Patients With Acute Ischemic Stroke.

BACKGROUND/OBJECTIVE: Alteplase may elevate international normalized ratio (INR) results, although the exact rate of elevation occurrence is not firmly established in the literature. The purpose of this study is to determine the occurrence rate of INR elevation following alteplase administration. We also aimed to determine what factors are independently associated with the development of elevated INR following alteplase administration for ischemic stroke. METHODS: We conducted a multicenter, retrospective, cohort study of patients who received alteplase for acute ischemic stroke. Patients were screened for baseline INR measurement and a repeat value within 24 hours of alteplase administration. The primary outcome was the percent of patients who experienced ≥0.4-point increase in INR. Secondary outcomes included the rate of adverse bleeding events and identification of factors independently associated with elevated INR following alteplase administration. RESULTS AND CONCLUSIONS: Two hundred and sixty-one patients were included, with 44 (16.9%) patients having an INR increase of 0.4 or more. Patients with an INR increase ≥0.4 experienced a nonstatistically significant increase in bleeding episodes (8.8% vs 18.2%; P = .10). We identified African American race (odds ratio, 3.48, 95% confidence interval, 1.5-7.6; P = .002) as an independent predictor of INR increase ≥0.04. An INR elevation is common following receipt of alteplase for ischemic stroke. Those of African American race were at increased risk of INR elevation; however, more studies are needed to determine whether these patients are at a higher bleeding risk as a result of INR elevation.

Characterisation of ICU sleep by a commercially available activity tracker and its agreement with patient-perceived sleep quality.

BACKGROUND: A low-cost, quantitative method to evaluate sleep in the intensive care unit (ICU) that is both feasible for routine clinical practice and reliable does not yet exist. We characterised nocturnal ICU sleep using a commercially available activity tracker and evaluated agreement between tracker-derived sleep data and patient-perceived sleep quality. PATIENTS AND METHODS: A prospective cohort study was performed in a 40-bed ICU at a community teaching hospital. An activity tracker (Fitbit Charge 2) was applied for up to 7 ICU days in English-speaking adults with an anticipated ICU stay ≥2 days and without mechanical ventilation, sleep apnoea, delirium, continuous sedation, contact isolation or recent anaesthesia. The Richards-Campbell Sleep Questionnaire (RCSQ) was administered each morning by a trained investigator. RESULTS: Available activity tracker-derived data for each ICU study night (20:00-09:00) (total sleep time (TST), number of awakenings (#AW), and time spent light sleep, deep sleep and rapid eye movement (REM) sleep) were downloaded and analysed. Across the 232 evaluated nights (76 patients), TST and RCSQ data were available for 232 (100%), #AW data for 180 (78%) and sleep stage data for 73 (31%). Agreement between TST (349±168 min) and RCSQ Score was moderate and significant (r=0.34; 95% CI 0.18 to 0.48). Agreement between #AW (median (IQR), 4 (2-9)) and RCSQ Score was negative and non-significant (r=-0.01; 95% CI -0.19 to 0.14). Agreement between time (min) spent in light (259 (182 to 328)), deep (43±29), and REM (47 (28-72)) sleep and RCSQ Score was moderate but non-significant (light (r=0.44, 95% CI -0.05 to 0.36); deep sleep (r=0.44, 95% CI -0.11 to 0.15) and REM sleep (r=0.44; 95% CI -0.21 to 0.21)). CONCLUSIONS: A Fitbit Charge 2 when applied to non-intubated adults in an ICU consistently collects TST data but not #AW or sleep stage data at night. The TST moderately correlates with patient-perceived sleep quality; a correlation between either #AW or sleep stages and sleep quality was not found.

Experimenting with At-Home General Chemistry Laboratories During the COVID-19 Pandemic.

During the COVID-19 pandemic, an at-home laboratory program was created and implemented for a section of the general chemistry course at the University of Southern California. The experiments were designed to only utilize safe household items and no special equipment. These laboratory activities, spanning over 4 weeks, focused on concepts usually covered in the final one-third of our second-semester chemistry laboratory, including pH, acid-base titrations, buffers, solubility, phase equilibria, and thermodynamics. In this article, we describe the design of the laboratories and our experience with this experiment, while also providing an assessment on how similar activities could be integrated profitably into a regular general chemistry course.

Quality of life in children and adolescents with obsessive-compulsive disorder: The Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q).

The current study examined quality of life (QOL) and its clinical correlates among 225 intensive treatment-seeking children and adolescents with obsessive-compulsive disorder (OCD) using the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q). Youth completed the PQ-LES-Q along with self-report measures assessing functional impairment, anxiety sensitivity, OCD symptoms, nonspecific anxiety, depression, and social anxiety. Parents completed measures on their child's anxiety, the presence of inattention/hyperactivity, depression, functional impairment, and frequency of family accommodation of symptoms. Contrary to expectation, child-reported OCD symptoms did not significantly predict QOL; however, lower overall QOL was strongly associated with the presence of comorbid major depressive disorder (g=3D -0.76) and slightly related to comorbid social phobia (g=3D -0.36). These results suggest that assessing and addressing comorbid conditions in the treatment of youth with OCD is an important component of intensive treatment.

Carbohydrate-supramolecular gels: Adsorbents for chromium(VI) removal from wastewater.

HYPOTHESIS: To overcome the contamination of water by heavy metals the adsorption of the pollutant on gel phases is an attractive solution since gels are inexpensive, potentially highly efficient and form a distinct phase while allowing diffusion of the contaminated water throughout the material. This work tests the chromium(VI) adsorbent capacity of new supramolecular gels for Chromium(VI) removal from wastewater. EXPERIMENTS: First hydrophobic imidazolium salts of carbohydrate anions were synthesised as new gelators. Subsequently, they were dissolved in a solvent by heating and, after cooling overnight, to give the formation of supramolecular gels. The properties of the resulting gels, such as thermal stability, mechanical strength, morphology, rheology, and kinetics of gel formation, were studied as a function of gelator structure, gelation solvent and pollutant removal efficiency. FINDINGS: Carbohydrate-derived gels showed the best removal capacity, i.e. 97% in 24 h. Interestingly, in one case, the reduction of chromium(VI) to chromium(III) also occurred after the adsorption process, and this phenomenon has been analysed using 1H NMR spectroscopy, IR spectroscopy, and SEM. The most efficient gel can reach an adsorption capacity of 598 mg/g in contrast to a value of 153 mg/g for the most effectively best hydrogels reported to date. The new gel can be also recycled up to 4 times. These findings suggest that these new, supramolecular hydrogels have potential applications in environmental remediation.

Polymorphism in M(H2PO2)3 (M = V, Al, Ga) compounds with the perovskite-related ReO3 structure.

Trivalent metal hypophosphites with the general formula M(H2PO2)3 (M = V, Al, Ga) adopt the ReO3 structure, with each compound displaying two structural polymorphs. High-pressure synchrotron X-ray studies reveal a pressure-driven phase transition in Ga(H2PO2)3 that can be understood on the basis of ab initio thermodynamics.

The capricious nature of iodine catenation in I2 excess, perovskite-derived hybrid Pt(iv) compounds.

Perovskite-derived hybrid platinum iodides with the general formula A2PtIVI6 (A = formamidinium FA and guanidinium GUA) accommodate excess I2 to yield hydrogen-bond-stabilized compounds where the I2 forms catenates with I- anions on the PtI6 octahedra.

Hydrogen Bonding Controls the Structural Evolution in Perovskite-Related Hybrid Platinum(IV) Iodides.

We describe the solid-state structural evolution in four hybrid hexaiodoplatinate(IV) compounds, demonstrating the increasingly important role that extended hydrogen bonding plays in directing the structure across the series. The compounds are A2PtI6, where A is one of the following amines: ammonium, NH4+; methylammonium, CH3NH3+; formamidinium, CH(NH2)2+; guanidinium, C(NH2)3+. These are closely related in structure and properties to the hybrid halide perovskites of lead(II) that have recently established their prowess in optoelectronics. The first three of these compounds crystallize in the vacancy-ordered double perovskite A2Pt□I6 (□ indicates a vacant site) structure in the K2PtCl6 archetype, despite the relatively large perovskite tolerance factors involved. The last compound, (GUA)2PtI6, crystallizes in a vacancy-ordered variant of the hexagonal CsNiCl3 structure: the K2MnF6 structure. A combination of solid-state 195Pt and 1H NMR spectroscopy and detailed density functional theory calculations helps to reveal structural trends and establish the hydrogen-bonding tendencies. The calculations and measured optical properties support the surprising observation in these iodosalt compounds that, for smaller A cations, the conduction bands are considerably disperse, despite lacking extended I-Pt-I connectivity.

Factors influencing the intentions of nurses and respiratory therapists to use automated external defibrillators during in-hospital cardiac arrest: a qualitative interview study.

OBJECTIVES: Nurses and respiratory therapists are seldom allowed to use automated external defibrillators (AED) during in-hospital cardiac arrest. This can result in significant time delays before defibrillation occurs and lower survival for cardiac arrest victims. We sought to identify barriers and facilitators to AED use by nurses and respiratory therapists. METHODS: We conducted semi-structured qualitative interviews with a purposeful sample of nurses and respiratory therapists. We developed the interview guide based on the constructs of the theory of planned behaviour, which elicits salient attitudes, social influences, and control beliefs potentially influencing the intent to use an AED. Interviews were recorded, transcribed verbatim, and analysed until achieving data saturation. Two independent reviewers performed inductive analyses to identify emerging categories and themes, and ranked them by frequency of the number of participants stating the topic. RESULTS: Demographics for the 24 interviewees include mean age 40.5, 79.2% female, 87.5% performed cardiopulmonary resuscitation (CPR), 29.2% defibrillated a patient. Identified attitudes pertained to the timeliness of defibrillation, patient survival, simplicity of AED use, accuracy of rhythm recognition, and harm to self or others. Social influences consisted of physician and hospital administration support of AED use. Control beliefs included training on AED use, policy allowing AED use, familiarity with AED, and task burden during resuscitation. CONCLUSIONS: Most nurses and respiratory therapists intended to use an AED if permitted to do so by a medical directive. Successful implementation would require educational initiatives focusing on safety and efficacy of AEDs, support from physicians and hospital administrators, and additional training on AED use.

Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats.

Postnatal administration of phencyclidine (PCP) in rodents causes major brain dysfunction leading to severe disturbances in behavior lasting into adulthood. This model is routinely employed to model psychiatric disorders such as schizophrenia, as it reflects schizophrenia-related brain disturbances including increased apoptosis, and disruptions to myelin and plasticity processes. Leucine-rich repeat and Immunoglobin-like domain-containing protein 1 (Lingo-1) is a potent negative regulator of both axonal myelination and neurite extension. The Nogo receptor (NgR)/tumor necrosis factor (TNF) receptor orphan Y (TROY) and/or p75 neurotrophin receptor (p75) complex, with no lysine (K) (WNK1) and myelin transcription factor 1 (Myt1) are co-receptors or cofactors in Lingo-1 signaling pathways in the brain. We have examined the developmental trajectory of these proteins in a neurodevelopmental model of schizophrenia using PCP to determine if Lingo-1 pathways are altered in the prefrontal cortex throughout different stages of life. Sprague-Dawley rats were injected with PCP (10 mg/kg) or saline on postnatal days (PN)7, 9, and 11 and killed at PN12, 5 or 14 weeks for measurement of Lingo-1 signaling proteins in the prefrontal cortex. Myt1 was decreased by PCP at PN12 (P=0.045), and at 14 weeks PCP increased Lingo-1 (P=0.037), TROY (P=0.017), and WNK1 (P=0.003) expression. This is the first study reporting an alteration in Lingo-1 signaling proteins in the rat prefrontal cortex both directly after PCP treatment in early development and in adulthood. We propose that Lingo-1 pathways may be negatively regulating myelination and neurite outgrowth following the administration of PCP, and that this may have implications for the cortical dysfunction observed in schizophrenia.

Effects of common GRM5 genetic variants on cognition, hippocampal volume and mGluR5 protein levels in schizophrenia.

GRM5 (coding for metabotropic glutamate receptor 5, mGluR5) is a promising target for the treatment of cognitive deficits in schizophrenia, but there has been little investigation of its association with cognitive and brain phenotypes within this disorder. We examined the effects of common genetic variation in GRM5 with cognitive function, hippocampal volume, and hippocampal mGluR5 protein levels in schizophrenia patients relative to healthy controls. Two independent GRM5 variants rs60954128 [C>T] and rs3824927 [G>T] were genotyped in a schizophrenia case/control cohort (n=249/261). High-resolution anatomical brain scans were available for a subset of the cohort (n=103 schizophrenia /78 control). All participants completed a standard set of neuropsychological tests. In a separate postmortem cohort (n=19 schizophrenia/20 controls), hippocampal mGluR5 protein levels were examined among individuals of different GRM5 genotypes. Schizophrenia minor allele carriers of rs60954128 had reduced right hippocampal volume relative to healthy controls of the same genotype (-12.3%); this effect was exaggerated in males with schizophrenia (-15.6%). For rs3824927, compared to major allele homozygotes, minor allele carriers with schizophrenia had lower Intelligence Quotients (IQ). Examination in hippocampal postmortem tissue showed no difference in mGluR5 protein expression according to genotype for either rs60954128 or rs3824927. While these genetic variants in GRM5 were associated with cognitive impairments and right hippocampal volume reduction in schizophrenia, they did not affect protein expression. Further study of these mechanisms may help to delineate new targets for the treatment of cognitive deficits in schizophrenia, and may be relevant to other disorders.