Connecting Law and Legislature: The Legacy of Ed Muskie

Edmund Muskie’s work impacts each of our lives, every day. The truth of this statement should become apparent as one explores the topics addressed in this symposium issue of the Maine Law Review, presented in honor of the centennial of Muskie’s birth. And yet, among the great American politicians, he may seem forgotten. His memory is in many ways confined to those who were present for his rise to national prominence in the 1960s, and to those steeped in environmental law, Maine political history, or one of the other fields in which he was most active. I will admit that prior to organizing the symposium from which this issue grew, I knew Muskie only as a caricature in a Hunter S. Thompson book about the 1972 presidential election

Monolith formation and ring-stain suppression in low-pressure evaporation of poly(ethylene oxide) droplets

When droplets of dilute suspensions are left to evaporate the final dry residue is typically the familiar coffee-ring stain, with nearly all material deposited at the initial triple line (Deegan et al, Nature, vol. 389, 1997, pp. 827-829). However, aqueous poly(ethylene oxide) (PEO) droplets only form coffee-ring stains for a very narrow range of the experimental parameters molecular weight, concentration and drying rate. Instead, over a wide range of values they form either a flat disk or a very distinctive tall central monolith via a four-stage deposition process which includes a remarkable bootstrap-building step. To predict which deposit will form, we present a quantitative model comparing the effects of advective build-up at the triple line to diffusive flux and use this to calculate a dimensionless number χ. By experimentally varying concentration and flux (using a low-pressure drying chamber), the prediction is tested over nearly two orders of magnitude in both variables and shown to be in good agreement with the boundary between disks and monoliths at χ ≈ 1.6

Dynamic Local Structure in Caesium Lead Iodide: Spatial Correlation and Transient Domains

Metal halide perovskites are multifunctional semiconductors with tunable structures and properties. They are highly dynamic crystals with complex octahedral tilting patterns and strongly anharmonic atomic behavior. In the higher temperature, higher symmetry phases of these materials, several complex structural features are observed. The local structure can differ greatly from the average structure and there is evidence that dynamic 2D structures of correlated octahedral motion form. An understanding of the underlying complex atomistic dynamics is, however, still lacking. In this work, the local structure of the inorganic perovskite CsPbI3 is investigated using a new machine learning force field based on the atomic cluster expansion framework. Through analysis of the temporal and spatial correlation observed during large-scale simulations, it is revealed that the low frequency motion of octahedral tilts implies a double-well effective potential landscape, even well into the cubic phase. Moreover, dynamic local regions of lower symmetry are present within both higher symmetry phases. These regions are planar and the length and timescales of the motion are reported. Finally, the spatial arrangement of these features and their interactions are investigated and visualized, providing a comprehensive picture of local structure in the higher symmetry phases

The clinical characterization of the adult patient with an anxiety or related disorder aimed at personalization of management

The clinical construct of “anxiety neurosis” was broad and poorly defined, so that the delineation of specific anxiety disorders in the DSM‐III was an important advance. However, anxiety and related disorders are not only frequently comorbid, but each is also quite heterogeneous; thus diagnostic manuals provide only a first step towards formulating a management plan, and the development of additional decision support tools for the treatment of anxiety conditions is needed. This paper aims to describe systematically important domains that are relevant to the personalization of management of anxiety and related disorders in adults. For each domain, we summarize the available research evidence and review the relevant assessment instruments, paying special attention to their suitability for use in routine clinical practice. We emphasize areas where the available evidence allows the clinician to personalize the management of anxiety conditions, and we point out key unmet needs. Overall, the evidence suggests that we are becoming able to move from simply recommending that anxiety and related disorders be treated with selective serotonin reuptake inhibitors, cognitive‐behavioral therapy, or their combination, to a more complex approach which emphasizes that the clinician has a broadening array of management modalities available, and that the treatment of anxiety and related disorders can already be personalized in a number of important respects

Directed evolution of GFP with non-natural amino acids identifies residues for augmenting and photoswitching fluorescence

Genetic code reprogramming allows proteins to sample new chemistry through the defined and targeted introduction of non-natural amino acids (nAAs). Many useful nAAs are derivatives of the natural aromatic amino acid tyrosine, with the para OH group replaced with useful but often bulkier substituents. Extending residue sampling by directed evolution identified positions in Green Fluorescent Protein tolerant to aromatic nAAs, including identification of novel sites that modulate fluorescence. Replacement of the buried L44 residue by photosensitive p-azidophenylalanine (azF) conferred environmentally sensitive photoswitching. In silico modelling of the L44azF dark state provided an insight into the mechanism of action through modulation of the hydrogen bonding network surrounding the chromophore. Targeted mutagenesis of T203 with aromatic nAAs to introduce π-stacking with the chromophore successfully generated red shifted versions of GFP. Incorporation of azF at residue 203 conferred high photosensitivity on sfGFP with even ambient light mediating a functional switch. Thus, engineering proteins with non-natural aromatic amino acids by surveying a wide residue set can introduce new and beneficial properties into a protein through the sampling of non-intuitive mutations. Coupled with retrospective in silico modelling, this will facilitate both our understanding of the impact of nAAs on protein structure and function, and future design endeavours

Pediatric lung transplantation: The years 1985 to 1992 and the clinical trial of FK 506

The application of lung transplantation to the pediatric population was a natural extension of the success realized in our adult transplantation program, which began in 1982. Twenty pediatric patients (age range 3 to 18 years) have had heart-lung (n = 11), double lung (n = 8), and single lung (n = 1) transplantation procedures. The causes of end-stage lung disease were primary pulmonary hypertension (n = 7), congenital heart disease (n = 5), cystic fibrosis (n = 4), pulmonary arteriovenous malformation (n = 2), graft- versus-host disease (n = 1), and desquamative interstitial pneumonitis (n = 1). Four (20%) patients had thoracic surgical procedures before the transplantation operation. The survival was 80% at a mean follow-up of 2 years. Immunosuppressive drugs included cyclosporine (n = 9) or FK 506 (n = 11) based therapy with azathioprine and steroids. Children were followed up by means of spirometry, transbronchial biopsy, and primed lymphocyte testing of bronchoalveolar lavage fluid. The mean number of treated episodes of rejection was 1.4 at 30 days, 0.5 at 30 to 90 days, and 1.4 at more than 90 days, and the first treated rejection episode occurred on average 28 days after the operation. Obliterative bronchiolitis developed in four (25%) of 16 patients surviving more than 100 days. Results of pulmonary function tests have remained good in almost all recipients. The greatest infectious risk was that of cytomegalovirus: one death and one case of pneumonia. Posttransplantation lymphoproliferative disease was diagnosed in two (12.5%) patients; both recovered. The most common complications were hypertension (25%) and postoperative bleeding (15%). Early results indicate that lung transplantation is a most promising therapy for children with severe vascular and parenchymal lung disease

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and ‘hard-to-reach’ patients

Background Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. Methods/design A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60–75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led ‘lung health check’ hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. Discussion If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. Trial registration This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number : ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015

Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry

Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology.Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999-2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005-2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution.Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance