Theory of melting of molecular crystals: the liquid crystalline phase

The theory of melting of molecular crystals developed by Pople and Karasz, which takes into account order-disorder processes in both the positions and orientations of the molecules, is discussed in a slightly modified form. The theory is an extension of the two-lattice model of Lennard-Jones and Devonshire so as to allow the molecules to take up two orientations on any site. It is assumed in this paper that the energy required for a molecule to diffuse to an interstitial site varies as V−4, as in the original formulation, but that the orientational barrier varies as V−3, in conformity with recent calculations of the orientational potential energy in nematic liquid crystals. The thermodynamic properties of the disordered system are evaluated relative to those of the perfectly ordered one using the Bragg-Williams approximation. For small orientational barriers, the theory predicts two transitions, a solid state rotational transition followed by a melting transition. For larger orientational barriers, the two transitions coalesce and there is a corresponding increase in the entropy of fusion. For even larger orientational barriers, the positional melting precedes the rotational melting and there occurs an intermediate phase, similar to the nematic mesophase, that has orientational order but no positional order. The predicted entropies of transition from the liquid crystal to the isotropic phase for a certain range of orientational barriers are comparable to those observed in nematic compounds. Theoretical curves are drawn for the degree of orientational order, the anomalous specific heat and thermal expansion as functions of temperature in the liquid crystalline range, and for the variation of the transition temperatures with pressure. The curves reproduce the trends in the physical properties of nematic liquid crystals

Theory of melting of molecular crystals II: solid-solid and melting transitions

The modified form of the Pople-Karasz theory of melting of inolecualr crystatls in a pervious paper is applied to study the thermodynamics of solid-solid and melting trasitions. The results are in substantial agreement with the predictions of the theory in its original form

Intranasal oxytocin in children and adolescents with autism spectrum disorder

BACKGROUND Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was −3.7 in the oxytocin group and −3.5 in the placebo group (least-squares mean difference, −0.2; 95% confidence interval, −1.5 to 1.0; P=0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks

Nucleophilic Addition to α\alpha, α\alpha-Dihalogenocarbonyl Compounds: Synthetic and Mechanistic Implications

Hydride reduction of dibromoketones $RCOCHBr_2$ $(R=Ph, CMe_3)$ gave $RCH(OH)CHBr_2$, which, when treated with KOH in $CCl_4$, gave aldehydes RCHBrCHO via intermediate bromoepoxides I. Grignard dialkylation of $Cl_2CHCOCl$ gave chloroalcs. $Cl_2CHCR_{12}OH$ $(II, R_1=Me, Ph, PhCH_2)$ in 85-96% yields. Similar rearrangement of II with KOH in $CCl_4$ gave the corresponding chloroaldehydes $R_{12}CClCHO$

Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B)

ObjectiveTo describe the rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B).MethodThis phase 2 clinical trial was designed to evaluate the use of intranasal oxytocin treatment to improve social difficulties in individuals with autism spectrum disorder (ASD). In total, 290 participants ages 3 to 17 years with a DSM-5 diagnosis of ASD were enrolled to receive 24 weeks of treatment with either oxytocin or a matched placebo at one of seven collaborating sites. Participants were subsequently treated with open-label oxytocin for 24 additional weeks. Post-treatment assessments were done approximately 4 weeks after treatment discontinuation. Plasma oxytocin and oxytocin receptor gene (OXTR) methylation level were measured at baseline, and week 8, 24 and 36 to explore potential relationships between these biomarkers and treatment response.ResultsThis report describes the rationale, design, and methods of the SOARS-B clinical trial.ConclusionsThere is a tremendous unmet need for safe and effective pharmacological treatment options that target the core symptoms of ASD. Several studies support the hypothesis that intranasal oxytocin could improve social orienting and the salience of social rewards in ASD, thereby enhancing reciprocal social behaviors. However, due to conflicting results from a number of pilot studies on the prosocial effects of exogenous oxytocin, this hypothesis remains controversial and inconclusive. SOARS-B is the best powered study to date to address this hypothesis and promises to improve our understanding of the safety and efficacy of intranasal oxytocin in the treatment of social deficits in children with ASD

Phase 4 trial of miltefosine for the treatment of Indian visceral leishmaniasis

Background. Visceral leishmaniasis (VL) is a major public health problem in Bihar, accounting for 90% of all cases in India. Development of high levels of resistance to various existing drugs necessitated the search for alternative orally administered drugs. Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children. Methods. An open, single-arm trial was designed to investigate the feasibility of treatment of VL patients with miltefosine in field conditions in 13 centers in Bihar. Results. The phase 4 study was conducted among 1132 adult and pediatric VL patients. Compliance was good, with 1084 (95.5%) patients completing the full 28-day treatment course. Nine hundred and seventy-one (85.8%) patients returned for the final cure assessment at 6 months after treatment. The final cure rate was 82% by intention to treat analysis and 95% by per protocol analysis (similar to the 94% cure rate in hospitalized patients). Treatment-related adverse events of common toxicity criteria grade 3 occurred in ~3% of patients, including gastrointestinal toxicity and rise in aspertate amino transferase, alanine amino transferase, or serum creatinine levels, similar to previous clinical experience. Conclusion. This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder

BackgroundExperimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.MethodsWe conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ.ResultsOf the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups.ConclusionsThis placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.)