Expanding the Effectiveness of the Massachusetts Comprehensive Permit Law by Eliminating Its Subsidy Requirement

The United States is in an affordable housing crisis; the problem is particularly acute in Massachusetts. Local zoning—especially in the form of density controls—is probably the most significant cause of the crisis. To mitigate the power of local zoning Massachusetts passed the Comprehensive Permit Law, which allows local zoning boards of appeals to override local zoning if certain requirements are met. One of those requirements, a government subsidy to the developer, has in some instances hindered the construction of affordable housing. Typically, a subsidy is required as an incentive to builders; otherwise their projects would not be profitable enough for them. In localities where real estate values are high, however, a density bonus (being able to develop more units on the same piece of land) may be enough to incentivize builders. In areas where subsidies are not necessary, project oversight, now largely performed by subsidizing agencies, should be performed by the Department of Housing and Community Development or local housing authorities

Next generation sequencing sheds light on the natural history of hepatitis C infection in patients that fail treatment

Background and rationale of the study: High rates of sexually-transmitted infection and reinfection with hepatitis C (HCV) have recently been reported in HIV-infected men who have sex with men and reinfection has also been described in monoinfected injecting drug users. The diagnosis of reinfection has traditionally been based on direct Sanger sequencing of samples pre and post-treatment, but not on more sensitive deep sequencing techniques. We studied viral quasispecies dynamics in patients who failed standard of care therapy in a high-risk HIV-infected cohort of patients with early HCV infection to determine whether treatment failure was associated with reinfection or recrudescence of pre-existing infection. Paired sequences (pre- and post- treatment) were analysed. The HCV E2 hypervariable region-1 was amplified using nested RT-PCR with indexed genotype-specific primers and the same products were sequenced using both Sanger and 454 pyrosequencing approaches. Results: Of 99 HIV-infected patients with acute HCV treated with 24-48 weeks of pegylated interferon alpha and ribavirin, 15 failed to achieve a sustained virological response (6 relapsed, 6 had a null response and 3 had a partial response). Using direct sequencing, 10/15 patients (66%) had evidence of a previously undetected strain post-treatment; in many studies, this is interpreted as reinfection. However, pyrosequencing revealed that 15/15 (100%) of patients had evidence of persisting infection. 6/15 (40%) patients had evidence of a previously undetected variant present in the post-treatment sample in addition to a variant that was detected at baseline. This could represent superinfection or a limitation of the sensitivity of pyrosequencing. Conclusion: In this high-risk group, the emergence of new viral strains following treatment failure is most commonly associated with emerging dominance of pre-existing minority variants rather than re-infection. Superinfection may occur in this cohort but reinfection is over-estimated by Sanger sequencing. (Hepatology 2014;

Drop-out rate from the liver transplant waiting list due to HCC progression in HCV-infected patients treated with direct acting antivirals.

BACKGROUND & AIM: concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following directly acting antiviral (DAA) therapy in cirrhotic patients with a prior complete oncological response have been raised. Data regarding the impact of HCV-treatment with DAAs on waiting list drop-out rates in patients with active HCC and HCV-related cirrhosis awaiting liver transplantation (LT) are lacking. MATERIALS AND METHODS: HCV-HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Centre were considered eligible for the study. After enrollment patients were divided into 2 groups, depending on whether they underwent DAAs treatment while awaiting LT or not. For each patient clinical, serological and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow-up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence-rates were calculated. RESULTS: twenty-three patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT-listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) drop-out events due to HCC-progression were registered (p = 0.9). No significant differences in terms of radiological progression were highlighted (p = 0.16). Nine out of 23 cases (39%) and 14/23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation or microvascular invasion. During post-LT FU, 1/8 DAAs treated patient (12,5%) and 1/12 control (8,3%) experienced HCC recurrence (p = 0.6). CONCLUSIONS: Viral eradication does not seem to be associated with an increased risk of drop-out due to neoplastic progression in HCV-HCC patients awaiting LT

The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: a prospective internally controlled interventional trial

Background Pathogen surveillance is challenging but crucial in children with cystic fibrosis—who are often nonproductive of sputum even if actively coughing—because infection and lung disease begin early in life. The role of sputum induction as a diagnostic tool for infection has not previously been systematically addressed in young children with cystic fibrosis. We aimed to assess the pathogen yield from sputum induction compared with that from cough swab and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage. Methods This prospective internally controlled interventional trial was done at the Children’s Hospital for Wales (Cardiff, UK) in children with cystic fibrosis aged between 6 months and 18 years. Samples from cough swab, sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage were matched for within-patient comparisons. Primary outcomes were comparative pathogen yield between sputum induction and cough swab for stage 1, and between sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage for stage 2. Data were analysed as per protocol. This study is registered with the UK Clinical Research Network (14615) and with the International Standard Randomised Controlled Trial Network Registry (12473810). Findings Between Jan 23, 2012, and July 4, 2017, 124 patients were prospectively recruited to the trial and had 200 sputum induction procedures for stage 1. 167 (84%) procedures were successful and the procedure was well tolerated. Of the 167 paired samples, 63 (38%) sputum-induction samples were pathogen positive compared with 24 (14%) cough swabs (p<0·0001; odds ratio [OR] 7·5; 95% CI 3·19–17·98). More pathogens were isolated from sputum induction than cough swab (79 [92%] of 86 vs 27 [31%] of 86; p<0·0001). For stage 2, 35 patients had a total of 41 paired sputum-induction and bronchoalveolar lavage procedures. Of the 41 paired samples, 28 (68%) were positive for at least one of the concurrent samples. 39 pathogens were isolated. Sputum induction identified 27 (69%) of the 39 pathogens, compared with 22 (56%; p=0·092; OR 3·3, 95% CI 0·91–12·11) on single-lobe, 28 (72%; p=1·0; OR 1·1, 95% CI 0·41–3·15) on two-lobe, and 33 (85%; p=0·21; OR 2·2, 95% CI 0·76–6·33) on six-lobe bronchoalveolar lavage. Interpretation Sputum induction is superior to cough swab for pathogen detection, is effective at sampling the lower airway, and is a credible surrogate for bronchoalveolar lavage in symptomatic children. A substantial number of bronchoscopies could be avoided if sputum induction is done first and pathogens are appropriately treated. Both sputum induction and six-lobe bronchoalveolar lavage provide independent, sizeable gains in pathogen detection compared with the current gold-standard two-lobe bronchoalveolar lavage. We propose that sputum induction and six-lobe bronchoalveolar lavage combined are used as standard of care for comprehensive lower airway pathogen detection in children with cystic fibrosis

Ionic Liquids to Replace Hydrazine

A method for developing safe, easy-to-handle propellants has been developed based upon ionic liquids (ILs) or their eutectic mixtures. An IL is a binary combination of a typically organic cation and anion, which generally produces an ionic salt with a melting point below 100 deg C. Many ILs have melting points near, or even below, room temperature (room temperature ionic liquids, RTILs). More importantly, a number of ILs have a positive enthalpy of formation. This means the thermal energy released during decomposition reactions makes energetic ILs ideal for use as propellants. In this specific work, to date, a baseline set of energetic ILs has been identified, synthesized, and characterized. Many of the ILs in this set have excellent performance potential in their own right. In all, ten ILs were characterized for their enthalpy of formation, density, melting point, glass transition point (if applicable), and decomposition temperature. Enthalpy of formation was measured using a microcalorimeter designed specifically to test milligram amounts of energetic materials. Of the ten ILs characterized, five offer higher Isp performance than hydrazine, ranging between 10 and 113 seconds higher than the state-of-the-art propellant. To achieve this level of performance, the energetic cations 4- amino-l,2,4-triazolium and 3-amino-1,2,4-triazolium were paired with various anions in the nitrate, dicyanamide, chloride, and 3-nitro-l,2,4-triazole families. Protonation, alkylation, and butylation synthesis routes were used for creation of the different salts

Dido and Musical Word Painting in Purcell\u27s Opera Dido and Aeneas (1680): A Storm of Emotions

My research is about Henry Purcell\u27s opera Dido and Aeneas. I am investigating this piece from a historical, cultural, and analytical perspective, specifically focusing on the role of musical text-painting. My data is derived from careful placement of my research within existing research by authors including J. Peter Burkholder, Donald Jay Grout, and Claude V. Palisca. Regarding the analysis of text painting, many textbooks have focused on the last three numbers of the opera ( Thy Hand, Belinda, When I am Laid in Earth, and With Drooping Wings ). Little analytical research has investigated text-painting in the music sung by the character Dido in the first act of the opera, a gap, which I aim to fill. The musical means by which Purcell achieves text-painting here go beyond the famous sighing figures (descending half-steps) and descending chromatic tetrachords of the last numbers. Rather, Purcell uses more nuanced musical idioms, such as large intervals for triumph; intricate, nervous rhythms for stubborn and distress; consecutive sixteenth notes for storms and fierce, and long slurs with dotted rhythms for flow and shake. Text-painting can have a very large effect on songs and bring forth so much emotion. It is evident throughout his whole opera, and a great example to teach others the significance it can have on a piece. My findings on text-painting help us to better understand the composer Purcell, and his operatic music

Dido and Musical Word Painting in Purcell\u27s Opera Dido and Aeneas (1680): A Storm of Emotions

My research is about Henry Purcell\u27s opera Dido and Aeneas. I am investigating this piece from a historical, cultural, and analytical perspective, specifically focusing on the role of musical text-painting. My data is derived from careful placement of my research within existing research by authors including J. Peter Burkholder, Donald Jay Grout, and Claude V. Palisca. Regarding the analysis of text painting, many textbooks have focused on the last three numbers of the opera ( Thy Hand, Belinda, When I am Laid in Earth, and With Drooping Wings ). Little analytical research has investigated text-painting in the music sung by the character Dido in the first act of the opera, a gap, which I aim to fill. The musical means by which Purcell achieves text-painting here go beyond the famous sighing figures (descending half-steps) and descending chromatic tetrachords of the last numbers. Rather, Purcell uses more nuanced musical idioms, such as large intervals for triumph; intricate, nervous rhythms for stubborn and distress; consecutive sixteenth notes for storms and fierce, and long slurs with dotted rhythms for flow and shake. Text-painting can have a very large effect on songs and bring forth so much emotion. It is evident throughout his whole opera, and a great example to teach others the significance it can have on a piece. My findings on text-painting help us to better understand the composer Purcell, and his operatic music