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Introduction Gallstone Ileus (GSI) is a rare cause of mechanical bowel obstruction secondary to impaction of an ectopic gallstone within the bowel lumen. Recurrent GSI is rare, accounting for less than 3% of SBO. The main risk factors for recurrence include a large choleduodenal fistula, an active fistula or faceted gallstones. There is currently no mainstay approach to managing GSI, with “single-stage” and “two-stage” options advocated. Case A 73-year-old lady presented with epigastric pain and vomiting, and was shown to have an obstructing gallstone in the distal ileum. She underwent a laparotomy and enterolithotomy and initially made a good recovery. However, she represented three months later with similar symptoms and was found to have a jejunal gallstone causing proximal small bowel obstruction. She underwent a second enterolithotomy, and is planned for an interval cholecystectomy. Discussion The management of recurrent GSI include one of three options: enterolithotomy alone, “single-stage” (enterolithotomy, cholecystectomy and fistula repair) or “two-stage” approach (enterolithotomy and interval cholecystectomy). The optimal approach in management is still debated. The traditionally taught two-stage approach demonstrates a lower mortality and recurrence rate and shorter index procedure in the unstable patient, requiring a skillset common to most general surgeons. However, with increasing reports of recurrent GSI, a single-stage approach during the index procedure has been advocated, citing decreased risk of cholecystitis, cholangitis and repeat laparotomy in the event of recurrence. Our patient underwent emergency enterolithotomy on both presentations, however there may support for a “single-step” approach in certain patient cohorts.

Infectious disease is a major cause of death worldwide, and novel methods capable of controlling the spread of disease are in high demand. This research presents a method of producing antimicrobial microcomposites by exploiting the powder-based nature of the Laser Sintering Additive Manufacturing process, via the incorporation of silver-containing additives. Silver phosphate glass additives in different formulations were designed to determine the effect of dissolution rate on the antimicrobial efficacy. These were characterised and successfully incorporated into polyamide 12 parts, without affecting the mechanical properties. The printed microcomposite parts displayed both bactericidal and antibiofouling effects against Gram-positive and Gram-negative bacteria in nutrient-poor conditions, with the efficacy found to be more sensitive to silver content than degradation rate.

In this Article, we consider the effects of filibuster change on judicial appointments, judicial voting, and opinion drafting. The filibuster effectively empowers a minority of forty-one Senators by requiring sixty votes to break off debate on a nomination. We develop a game-theoretic model that explains that the elimination of the filibuster changed the relevant “pivotal Senator” whose support was necessary to secure a nomination. Freed of the power of the minority of Senators, Presidents ought to exercise freer rein in naming judicial nominees closer to their preferred ideology. Moreover, sitting judges who seek elevation to a higher court ought to alter their “signal” that they would be good candidates to match the preferences of the newly-relevant pivotal Senator. To test our hypotheses empirically, we use the 2013 elimination of the filibuster in the U.S. Senate for lower federal court judicial nominations as an exogenous shock. We explore how the change in the filibuster rule affected the characteristics of judges President Obama nominated to the federal courts. We find statistically-significant shifts in the background characteristics of judges confirmed to the federal courts of appeals after the elimination of the filibuster. Compared to the earlier Obama appointees, these judges were more likely to be female, slightly younger, and to have previously clerked for a liberal judges, but less likely to be non-white. In addition, we find that there was a statistically-significant increase in the confirmation of judges with liberal ideologies, as measured by their common space campaign finance scores. These liberal ideologies mapped onto actual votes in politically-charged cases. Compared to Obama judges confirmed before the rule change, the judges were more likely to cast pro-choice votes in abortion cases and anti-death penalty votes in death penalty cases. We also find evidence that the elimination of the filibuster had a polarizing effect on sitting federal district judges, especially those with a greater chance of promotion to the courts of appeals. Using computational content analysis, we find that, after the change in the filibuster rule, Democratic judges were more likely to use politically-charged words signaling their very liberal ideological positions in abortion opinions and Republican judges were more likely to use words signaling their conservative views. These findings are useful in assessing the desirability of restoring the judicial filibuster, as well as to the debate over the retention of the legislative filibuster.

Purpose X-Ray-computed micro-tomography (micro-CT) is relatively well established in additive manufacturing as a method to determine the porosity and geometry of printed parts and, in some cases, the presence of inclusions or contamination. This paper aims to demonstrate that micro-CT can also be used to quantitatively analyse the homogeneity of micro-composite parts, in this case created using laser sintering (LS). Design/methodology/approach LS specimens were manufactured in polyamide 12 with and without incorporation of a silver phosphate glass additive in different sizes. The specimens were scanned using micro-CT to characterise both their porosity and the homogeneity of dispersion of the additive throughout the volume. Findings This work showed that it was possible to use micro-CT to determine information related to both porosity and additive dispersion from the same scan. Analysis of the pores revealed the overall porosity of the printed parts, with linear elastic fracture mechanics used to identify any pores likely to lead to premature failure of the parts. Analysis of the additive was found to be possible above a certain size of particle, with the size distribution used to identify any agglomeration of the silver phosphate glass. The particle positions were also used to determine the complete spatial randomness of the additive as a quantitative measure of the dispersion. Practical implications This shows that micro-CT is an effective method of identifying both porosity and additive agglomeration within printed parts, meaning it can be used for quality control of micro-composites and to validate the homogeneity of the polymer/additive mixture prior to printing. Originality/value This is believed to be the first instance of micro-CT being used to identify and analyse the distribution of an additive within a laser sintered part.

2-deoxy-D-Ribose (2dDR) was first identified in 1930 in the structure of DNA and discovered as a degradation product of it later when the enzyme thymidine phosphorylase breaks down thymidine into thymine. In 2017, our research group explored the development of wound dressings based on the delivery of this sugar to induce angiogenesis in chronic wounds. In this review, we will survey the small volume of conflicting literature on this and related sugars, some of which are reported to be anti-angiogenic. We review the evidence of 2dDR having the ability to stimulate a range of pro-angiogenic activities in vitro and in a chick pro-angiogenic bioassay and to stimulate new blood vessel formation and wound healing in normal and diabetic rat models. The biological actions of 2dDR were found to be 80 to 100% as effective as VEGF in addition to upregulating the production of VEGF. We then demonstrated the uptake and delivery of the sugar from a range of experimental and commercial dressings. In conclusion, its pro-angiogenic properties combined with its improved stability on storage compared to VEGF, its low cost, and ease of incorporation into a range of established wound dressings make 2dDR an attractive alternative to VEGF for wound dressing development.

Microbial keratitis occurs from the infection of the cornea by fungi and or bacteria. It remains one of the most common global causes of irreversible blindness accounting for 3.5% (36 million) of blind people as of 2015. This paper looks at the use of a bacteria binding polymer designed to bind Staphylococcus aureus and remove it from the corneal surface. Mechanical unbinding measurements were used to probe the interactions of a thermo-active bacteria-binding polymer, highly-branched poly(N-isopropyl acrylamide), functionalised with modified vancomycin end groups (HB-PNIPAM-Van) to bacteria placed on rabbit corneal surfaces studied ex-vivo. This was conducted during sequential temperature phase transitions of HB-PNIPAM-Van-S. aureus below, above and below the lower critical solution temperature (LCST) in 3 stages, in-vitro, using a novel micro-bead force spectroscopy (MBFS) approach via atomic force microscopy (AFM). The effect of temperature on the functionality of HB-PNIPAM-Van-S. aureus showed that the polymer-bacteria complex reduced the work done in removing bacterial aggregates at T > LCST (p p 2.5 µm) increased (p 2.5 µm) compared to S. aureus aggregates only. Here, we present the first study using AFM to assess the reversible mechanical impact of a thermo-active polymer-binding bacteria on a natural corneal surface.

Skin has a highly regulated pH environment of around pH 7.2 but with an acid barrier mantle of around pH 5.5. Trauma, inflammation, and infection are all thought to disrupt this pH environment but ...

Branched poly(N-isopropylacrylamide) was functionalized with Amphotericin B (AmB) at the chain ends to produce an antifungal material. The polymer showed antifungal properties against AmB-sensitive strains of Candida albicans, Fusarium keratoplasticum and Aspergillus flavus (minimal inhibitory concentration ranged from 5 to 500 µg ml−1) but was not effective against an AmB resistant strain of C. albicans nor against Candida tropicalis. The polymer end groups bound to the AmB target, ergosterol, and the fluorescence spectrum of a dye used as a solvatochromic probe, Nile red, was blue shifted indicating that segments of the polymer became desolvated on binding. The polymer was less toxic to corneal and renal epithelial cells and explanted corneal tissue than the free drug. Also, the polymer did not induce reactive oxygen species release from peripheral blood mononuclear cells, nor did it cause a substantial release of the proinflammatory cytokines, tumour necrosis factor-α and interleukin-1β (at 0.5 mg ml−1).

The global challenge of antimicrobial resistance is of increasing concern, and alternatives to currently used antibiotics or methods to improve their stewardship are sought worldwide. Microbial biofilms, complex 3D communities of bacteria and/or fungi, are difficult to treat with antibiotics for several reasons. These include their protective coats of extracellular matrix proteins which are difficult for antibiotics to penetrate. Nanoparticles (NP) are one way to rise to this challenge; whilst they exist in many forms naturally there has been a profusion in synthesis of these small (

The physiological wound healing process involves a cascade of events which could be affected by several factors resulting in chronic, non-healing wounds. The latter represent a great burden especially when bacterial biofilms are formed. The rise in antibiotic resistance amongst infectious microorganisms leads to the need of novel approaches to treat this clinical issue. In this context, the use of advanced biomaterials, which can enhance the physiological expression and secretion of the growth factors involved in the wound healing process, is gaining increasing attention as a robust and appealing alternative approach. Among them, mesoporous glasses are of particular interest due to their excellent textural properties and to the possibility of incorporating and releasing specific therapeutic species, such as metallic ions. One of the most attractive therapeutic ions is copper thanks to its proangiogenic and antibacterial effects. In this contribution, copper containing mesoporous glass nanoparticles were proposed as a multifunctional device to treat chronic wounds. The developed nanoparticles evidenced a very high specific surface area (740 m2/g), uniform pores of 4 nm and an almost total release of the therapeutic ion within 72 h of soaking. The produced nanoparticles were biocompatible and, when tested against Gram positive and Gram negative bacterial species, demonstrated antibacterial activity against both planktonic and biofilm bacteria in 2D cell monolayers, and in a 3D human model of infected skin. Their proangiogenic effect was tested with both the aortic ring and the chick chorioallantoic membrane assays and an increase in endothelial cell outgrowth at a concentration range between 30 and 300 ng/mL was shown. Overall, in this study biocompatible, multifunctional Cu-containing mesoporous glass nanoparticles were successfully produced and demonstrated to exert both antibacterial and proangiogenic effects.

Infectious diseases (exacerbated by antimicrobial resistance) cause death, loss of quality of life and economic burden globally. Materials with inherent antimicrobial properties offer the potential to reduce the spread of infection through transfer via surfaces or solutions, or to directly reduce microbial numbers in a host if used as implants. Additive Manufacturing (AM) techniques offer shorter supply chains, faster delivery, mass customisation and reduced unit costs, as well as highly complicated part geometries which are potentially harder to clean and sterilise. Here, we present a new approach to introducing antibacterial properties into AM, using Laser Sintering, by combining antimicrobial and base polymer powders prior to processing. We demonstrate that the mechanical properties of the resultant composite parts are similar to standard polymer parts and reveal the mode of the antibacterial activity. We show that antibacterial activity is modulated by the presence of obstructing compounds in different experimental media, which will inform appropriate use cases. We show that the material is not toxic to mammalian cells. This material could be quickly used for commercial products, and our approach could be adopted more generally to add new functionality to Laser Sintered parts.

Bacterial quorum sensing has been implicated in a number of pathogenic bacterial processes, such as biofilm formation, making it a crucial target for developing materials with a novel antibiotic mode of action. This paper describes poly(N-isopropyl acrylamide) that has been covalently linked, at multiple chain ends, to homoserine lactone to give a highly branched polymer functionalized with a key messenger molecule implicated in QS. This novel functional material has shown promising anti-QS activity in a Chromobacterium violaceum assay.

Pharmacy benefit managers (PBMs) manage the drug benefits for over 95 percent of Americans with prescription drug coverage. However, conflicts of interest inherent in the PBM business model create perverse incentives for drug price increases. The most significant conflict of interest arises from manufacturer rebates paid to PBMs. PBMs negotiate rebates from drug manufacturers in exchange for giving the manufacturers’ drugs preferred status on a health plan’s formulary. Because the rebates paid to PBMs are typically a percentage of a drug’s list price, drug makers are pressured to increase list prices in order to satisfy PBMs’ demands for higher rebates. Although a portion of the increasing rebate dollars may eventually find its way to patients in the form of lower co-pays, many patients still suffer from the list prices increases. This Article analyzes various proposals to rein in PBM rebates and asserts that, compared to the other proposals, a point-of-sale rebate system maintains many of the benefits of selective contracting while minimizing incentives to increase drug list prices.

This paper explores the use of low-frequency-low-amplitude acoustic vibration on biofilm formation. Biofilm development is thought to be governed by a diverse range of environmental signals and much effort has gone into researching the effects of environmental factors including; nutrient availability, pH and temperature on the growth of biofilms. Many biofilm-forming organisms have evolved to thrive in mechanically challenging environments, for example soil yet, the effects of the physical environment on biofilm formation has been largely ignored. Exposure of Pseudomonas aeruginosa to vibration at 100, 800 and 1600Hz for 48 hours, resulted in a significant increase in biofilm formation compared with the control, with the greatest growth seen at 800Hz vibration. The results also show that this increase in biofilm formation is accompanied with an increase in P. aeruginosa cell number. Acoustic vibration was also found to regulate the spatial distribution of biofilm formation in a frequency-dependent manner. Exposure of Staphylococcus aureus to acoustic vibration also resulted in enhanced biofilm formation with the greatest level of biofilm being formed following 48hours exposure at 1600Hz. These results show that acoustic vibration can be used to control biofilm formation and therefore presents a novel and potentially cost effective means to manipulate the development and yield of biofilms in a range of important industrial and medical processes.

Microbial keratitis can arise from penetrating injuries to the cornea. Corneal trauma promotes bacterial attachment and biofilm growth, which decrease the effectiveness of antimicrobials against microbial keratitis. Improved therapeutic efficacy can be achieved by reducing microbial burden prior to antimicrobial therapy. This paper assesses a highly-branched poly(N-isopropyl acrylamide) with vancomycin end groups (HB-PNIPAM-van), for reducing bacterial attachment and biofilm formation. The polymer lacked antimicrobial activity against Staphylococcus aureus, but significantly inhibited biofilm formation (p = 0.0008) on plastic. Furthermore, pre-incubation of S. aureus cells with HB-PNIPAM-van reduced cell attachment by 50% and application of HB-PNIPAM-van to infected ex vivo rabbit corneas caused a 1-log reduction in bacterial recovery, compared to controls (p = 0.002). In conclusion, HB-PNIPAM-van may be a useful adjunct to antimicrobial therapy in the treatment of corneal infections.

Drug compounding is the practice of mixing, combining, or altering drug ingredients to create a product that meets the medical needs of a patient whose needs cannot otherwise be met with commercially-available products. Although drug compounding fills a critical need for many patients, it has also given rise to significant drug safety concerns, fraud, and anticompetitive practices. Every year, many patients experience harmful side effects and even death from compounded drugs that are contaminated or made in excessive potency because of pharmacist error. The ability of pharmacies to make and dispense drugs outside of the typical channels has also given rise to extensive fraud. In addition, some rogue pharmacies earn significant profits by mass-producing compounded drugs that are essentially copies of commercially-available drugs. Many of the drug safety problems, fraudulent practices, and anti-competitive behaviors are facilitated by regulatory gaps in the oversight of drug compounding. Traditional drug manufacturers must prove that their drugs are safe and effective and manufactured in accordance with current good manufacturing practices (CGMPs) in order to obtain FDA approval. In contrast, compounders need not obtain FDA approval for their drugs before selling them, and most compounders do not have to produce drugs in accordance with CGMPs. Moreover, traditional drug manufacturing facilities are subject to routine inspection by the FDA to ensure they are in compliance with CGMPs and that there are no other safety or quality concerns. In contrast, most compounders are not primarily overseen by the FDA but by state boards of pharmacy that are less consistent in their oversight — fewer than half of the states even conduct routine inspections of compounding pharmacies. Finally, whereas traditional manufacturers are required to report adverse events involving their drugs to the FDA, most compounders do not have to report adverse events to either the FDA or state regulatory authorities. This Article explains the regulatory gaps in drug compounding that give rise to drug safety problems, fraud, and anti-competitive behavior and proposes various measures that could be taken to close the gaps in order to protect patients, payors, and innovation.

In this article, we explore the relationship between political parties’ campaign contributions and partisan voting among state supreme court judges who won partisan elections. Using three different measures of partisan voting, we find that contributions from political parties are associated with partisanship in judicial decision making. Campaign contributions from political parties are related to judicial voting in the party-preferred ideological direction and to cohesive voting among judges from the same political party. We find that the relationship between party contributions and partisan voting is stronger for Republican judges than for Democratic judges.

Solid tumours vary in sensitivity to the vascular disrupting agent combretastatin\ud A-4 3-O-phosphate (CA4P), but underlying factors are poorly understood. The\ud signaling sphingolipid, sphingosine-1-phosphate (S1P), promotes vascular barrier\ud integrity by promoting assembly of VE-cadherin/β-catenin complexes. We tested the\ud hypothesis that tumour pre-treatment with S1P would render tumours less susceptible\ud to CA4P.\ud S1P (1μM) pretreatment attenuated an increase in endothelial cell (HUVEC)\ud monolayer permeability induced by 10μM CA4P. Intravenously administered S1P\ud (8mg/kg/hr for 20 minutes then 2mg/kg/hr for 40 minutes), reduced CA4Pinduced\ud (30mg/kg) blood fow shut-down in fbrosarcoma tumours in SCID mice\ud (n≥7 per group), as measured by tumour retention of an intravenously administered\ud fuorescent lectin. A trend towards in vivo protection was also found using laser\ud Doppler fowmetry. Immunohistochemical staining of tumours ex vivo revealed\ud disrupted patterns of VE-cadherin in vasculature of mice treated with CA4P, which\ud were decreased by pretreatment with S1P. S1P treatment also stabilized N-cadherin\ud junctions between endothelial cells and smooth muscle cells in culture, and stabilized\ud tubulin flaments in HUVEC monolayers.\ud We conclude that the rapid shutdown of tumour microvasculature by CA4P is\ud due in part to disruption of adherens junctions and that S1P has a protective effect\ud on both adherens junctions and the endothelial cell cytoskeleton.

The behavior of a linear copolymer of N-isopropylacrylamide with pendant vancomycin functionality was compared to an analogous highly branched copolymer with vancomycin functionality at the chain ends. Highly branched poly(N-isopropylacrylamide) modified with vancomycin (HB-PNIPAM-van) was synthesized by functionalization of the HB-PNIPAM, prepared using reversible addition-fragmentation chain transfer polymerization. Linear PNIPAM with pendant vancomycin functionality (L-PNIPAM-van) was synthesized by functionalization of poly(N-isopropylacrylamide-co-vinyl benzoic acid). HB-PNIPAM-van aggregated S. aureus effectively, whereas the L-PNIPAM-van polymer did not. It was found that when the HB-PNIPAM-van was incubated with S. aureus the resultant phase transition provided an increase in the intensity of fluorescence of a solvatochromic dye, nile red, added to the system. In contrast, a significantly lower increase in fluorescence intensity was obtained when L-PNIPAM-van was incubated with S. aureus. These data showed that the degree of desolvation of HB-PNIPAM-van was much greater than the desolvation of the linear version. Using microcalorimetry, it was shown that there were no significant differences in the affinities of the polymer ligands for d-Ala-d-Ala and therefore differences in the interactions with bacteria were associated with changes in the probability of access of the polymer bound ligands to the d-Ala-d-Ala dipeptide. The data support the hypothesis that generation of polymer systems that respond to cellular targets, for applications such as cell targeting, detection of pathogens etc., requires the use of branched polymers with ligands situated at the chain ends.

Consumer protection acts (CPAs) developed with the goal to protect American consumers from fraudulent, deceptive and unfair business practices. Initially, Congress, through the FTC Act, sought to define and deter conduct that the existing legal system largely failed to remedy. Subsequently, states localized and individualized these rights while maintaining a careful balance between protecting consumers and preventing the proliferation of lawsuits that harm both consumers and businesses. But in recent decades, this thoughtful balance has yielded to damaging legislative and judicial overcorrections at the state level with a common theoretical mistake: the assumption that more CPA litigation automatically yields more consumer protection. The result has been an explosion in consumer protection litigation, which serves no social function and for which consumers pay indirectly through higher prices and reduced innovation. Using data on state and federal CPA litigation from 2000-2013, we find substantial increases in CPA litigation in both, with federal litigation growing almost twice as fast in federal than state courts (a cumulative average growth rate of 6.1 percent vs. 3.4 percent). We also find that the financial crisis appears to have played a large role in the recent growth in CPA litigation — the financial services industry is the most common target for private CPA actions in a set of cases we sample, and a large proportion of these cases involve debt collection or federal lending or housing statutes. We conclude that although the entire suite of expansive provisions in CPAs — enhanced damages, class actions, attorneys fees, and eliminating the need to show harm — are responsible for the explosion in private CPA litigation, from a social standpoint, requiring consumers to show cognizable harm would be the most efficient reform.

Bioactive glasses (BG) are versatile materials for various biomedical applications, including bone regeneration and wound healing, due to their bone bonding, antibacterial, osteogenic, and angiogenic properties. In this study, we aimed to enhance the antibacterial activity of SiO2-CaO mesoporous bioactive glass nanoparticles (MBGN) by incorporating silver (Ag) through a surface modification approach. The modified Ag-containing nanoparticles (Ag-MBGN) maintained spherical shape, mesoporous structure, high dispersity, and apatite-forming ability after the surface functionalization. The antibacterial activity of Ag-MBGN was assessed firstly using a planktonic bacteria model. Moreover, a 3D tissue-engineered infected skin model was used for the first time to evaluate the antibacterial activity of Ag-MBGN at the usage dose of 1 mg/mL. In the planktonic bacteria model, Ag-MBGN exhibited a significant antibacterial effect against both Pseudomonas aeruginosa and Staphylococcus aureus in comparison to non-engineered (Ag-free) MBGN and the blank control. Moreover, Ag-MBGN did not show cytotoxicity towards fibroblasts at the usage dose. However, in the 3D infected skin model, Ag-MBGN only demonstrated antibacterial activity against S. aureus whereas their antibacterial action against P. aeruginosa was inhibited. In conclusion, surface modification by Ag incorporation is a feasible approach to enhance the antibacterial activity of MBGN without significantly impacting their morphology, polydispersity, and apatite-forming ability. The prepared Ag-MBGN are attractive building blocks for the development of 3D antibacterial scaffolds for tissue engineering.

This report empirically examines the allocation of settlements and awards in no-injury class actions among plaintiffs, attorneys, and cy pres funds. The results are based on my study of 432 no-injury class action settlements and trial awards from 2005-2015. The study finds that, on average, 60 percent of the total monetary award paid by the defendants was allocated to the plaintiffs’ class and 37.9 percent was allocated to attorneys’ fees. However, because many settlements disperse the unclaimed portion of the settlement fund to a cy pres fund, the funds available to class members at the time of settlement may significantly overstate the actual amount class members ultimately receive. Although 60 percent of the total monetary award may be available to class members, in reality, they typically receive less than 9 percent of the total. In comparison, class counsel receives an average of 37.9 percent of available funds, over 4 times the funds typically distributed to the class. A result in which plaintiffs recover less than 10 percent of the award, with the rest going to lawyers or unrelated groups, clearly does not achieve the compensatory goals of class actions. Instead, the costs of no-injury class actions are passed on to consumers in the form of higher prices, lower product quality, and reduced innovation.

Polymyxin peptide conjugated to the end groups of highly branched poly(N-isopropyl acrylamide) was shown to bind to a Gram negative bacterium, Pseudomonas aeruginosa . The nonbound polymer had a lower critical solution temperature (LCST) above 60 °C. However, binding caused aggregation, which was disrupted on cooling of the bacteria and polymer mixture. The data indicate that polymer binding of bacteria occurred by interaction of the end groups with lipopolysaccharide and that the binding decreased the LCST to below 37 °C. Cooling then progressed the polymer/bacteria aggregate through a bound LCST into an open polymer coil conformation that was not adhesive to P. aeruginosa .

Wound infection is a common complication often resulting in delayed healing with adverse clinical and financial consequences. Current antimicrobial treatments are far from ideal, side effects can include both bacterial resistance and toxicity. As a result, a great deal of effort over the last 20 years has been spent on investigating new forms of antimicrobial dressings. Here, we report the unexpected antimicrobial activity of a relatively new biocompatible thermo-responsive PHPMA–PMPC–PHPMA triblock copolymer gelator [where PHPMA denotes poly(2-hydroxypropyl methacrylate) and PMPC denotes poly(2-(methacryloyloxy)ethyl phosphorylcholine)]. In a radial diffusion assay, a 20% w/v copolymer gel produced an inhibitory zone up to six times greater than the corresponding control against Staphylococcus aureus. Similarly, in a broth inhibition assay the same copolymer reduced bacterial growth by 45% compared with control experiments conducted in the absence of any copolymer. Moreover, addition of the copolymer to a 3D-infected skin model reduced bacterial recovery by 38% compared to that of controls over 24–48 h. This is particularly relevant since these antimicrobial triblock copolymers were recently shown to be non-toxic when exposed to a tissue-engineered skin model. This antimicrobial activity was also successfully immobilised by grafting PMPC–PHPMA diblock copolymer brushes onto silicon wafers. Our results indicate that both PMPC–PHPMA diblock and PHPMA homopolymer brushes exhibit antimicrobial activity. Our hypothesis for the mode of action is that the moderately hydrophobic PHPMA chains penetrate the bacterial membrane, causing leakage of the cell contents. In summary, these gels and surfaces offer a promising new approach to antimicrobial dressings.

While infected skin wounds are on the increase because of ageing populations, rising incidence of diabetes, and antibiotic resistance, we lack relevant in vivo or in vitro models to study many aspects of bacterial interaction with skin. The aim of this study was to develop three-dimensional models of normal human skin to study bacterial infection. The common dermatological pathogens Staphylococcus aureus and Pseudomonas aeruginosa were used to infect tissue-engineered skin, and the course of infection in the skin was examined over several days. Two forms of model were developed-one in which bacteria were introduced directly to 10 mm wounds in the epidermis, and another in which wounds were created by burning a 4 mm hole in the center of the tissue before inoculation. The bacteria flourished within the engineered skin, and colonized the upper epidermal layers before invasion into the dermis. Infection with P. aeruginosa caused a loss of epidermis and de-keratinization of the skin constructs, as well as partial loss of basement membrane. These novel complex human skin infection models could be used to investigate microbial invasion of normal skin epithelium, basement membrane, and connective tissue, and as a model to study approaches to reduce bacterial burden in skin wounds.

Tort reform may not affect all segments of society equally. Studies have shown that many tort reforms disproportionately reduce compensation to women, children, the elderly, disadvantaged minorities, and less affluent people. This study goes beyond tort reform’s disproportionate effect on compensation, to explore whether tort reform also has a disproportionate effect on accidental death rates. We explain that, theoretically, tort reform’s care-level effects and activity-level effects may disproportionately impact the accident rates of different groups. Using the most accurate, comprehensive data on medical malpractice tort reforms and state-level data from 1980-2000, we examine empirically whether tort reforms indeed have such a disproportionate effect. The results from our empirical analysis are consistent with our theoretical predictions. We find that the impact of tort reform varies substantially among demographic groups. When we consider the net effect of all the reforms in our study together, our results suggest that women, children, and the elderly do not enjoy tort reform’s benefits as much as men and middle-aged people. In fact, they might even be harmed by reform.

Summary The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl/OCl − ) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized an imaging probe, sulfonaphthoaminophenyl fluorescein (SNAPF), that selectively reacts with HOCl. SNAPF detects HOCl produced by stimulated MPO-expressing cells cultured from human whole blood, as well as HOCl from bone marrow (BM)-derived macrophages isolated from transgenic mice that express human MPO. Two lines of evidence indicate that SNAPF permits the in vivo imaging of HOCl production. First, we used this approach to demonstrate HOCl production by neutrophils in experimental murine peritonitis. Second, we detected HOCl production by MPO expressing cells in human atherosclerotic arteries. Thus, fluorescence reflectance imaging by SNAPF may provide a valuable noninvasive molecular imaging tool for implicating HOCl and MPO in the damage of inflamed tissues.

Theory suggests that tort reform could have two possible impacts on accidents. Reforms could increase accidents as tortfeasors internalize less of the cost of externalities and have less incentive to reduce the risk of accidents. Alternatively, tort reforms could decrease accidents as lower expected liability costs result in lower prices, enabling consumers to buy more risk‐reducing products such as medicines, safety equipment, and medical services, and could result in consumers increasing precautions to avoid accidents. We test these effects by examining the relationship between tort reform and non‐motor‐vehicle accidental death rates using panel data techniques. We find that noneconomic damage caps, a higher evidence standard for punitive damages, product liability reform, and prejudgment interest reform are associated with fewer accidental deaths, while reforms to the collateral source rule are associated with increased deaths. Overall, the tort reforms in the states between 1981 and 2000 are associated with an estimated 24,000 fewer accidental deaths.

I. INTRODUCTION The contemporary debate over capital punishment involves a number of important arguments based on either moral principles or social welfare considerations. The primary social welfare issue, viewed as "the most important single consideration for both sides in the death penalty controversy," is whether capital punishment deters capital crimes; see, for example, Zimring and Hawkins (1986). This issue is also of great interest to several states that are currently considering a change in their death penalty laws. (1) Psychologists and criminologists studied the death penalty initially and reported no deterrent effect; see, for example, Sellin (1959) and Eysenck (1970). Economists joined the debate later, with Ehrlich's 1975 and 1977 studies that report a significant deterrent effect applying regression analysis to U.S. aggregate data for 1933-69 and state-level data for 1940 and 1950. Ensuing studies use either Ehrlich's data with different regression specifications--different regressors, functional form, or endogenous variables--or postmoratorium data with a variant of Ehrlich's regression model. Results range from a substantial deterrent effect to no effect or a small adverse effect. (2) This study uses a new approach to advance the deterrence literature. We exploit an important characteristic that other studies have not considered: the experimental nature of the moratorium that the Supreme Court imposed on executions during the 1970s. The moratorium can be viewed as an exogenously imposed "judicial experiment." The experiment's effect on murder rates provides evidence about the deterrent effect of capital punishment. We compare the murder rate for each state immediately before and after it suspended or reinstated the death penalty. Many factors that affect crime--for example, law enforcement, judicial, demographic, and economic variables--change only slightly over a short period of time. Therefore, changes in a state's murder rate quickly following a change in its death penalty law can be attributed to the legal change. Also, there are considerable cross-state variations in the timing and duration of the moratorium that began and ended in different years in different states, ranging from four to thirty years (see Tables 1 and 2). (3) These variations can strengthen our comparison-based inference, because observing similar changes in murder rates immediately after the same legal change in different years and in various states provides compelling evidence of the moratorium's effect on murder. Moreover, our analysis benefits from the experiences of the states that suspended and reinstated their death penalty statutes several times. (4) For states that experience similar murder rate changes after suspensions (or reinstatements) in different crime, economic, and demographic environments, the contribution of the legal change to murder is paramount. We supplement the before-and-after comparisons with time-series and panel data regression analyses. Unlike most existing studies, we use both pre- and postmoratorium data. The regressions disentangle the effect of having death penalty laws on murder from the effect of actual executions on murder. Basing our inference on two different approaches allows us to corroborate our findings and also detract from the modeling concerns voiced at previous studies that use only regression analysis. We also apply a battery of tests to examine the robustness of the findings. These include regression sensitivity checks with 89 additional regression equations that differ from our base models in regressors, functional form, data, and estimation method. In addition, we test whether the moratorium has an effect on property crimes that are not punishable by death. If the relationship between the moratorium and these crimes is similar to the relationship between the moratorium and murder, then we should suspect that murder rate changes are the result of broader trends in criminal behavior affecting all crimes. …

Many early empirical studies found that prison growth is associated with substantial reductions in crime. However, recent studies find no statistically significant relationship between growth in prison populations and crime. Even more striking, one recent study finds that, in certain circumstances, imprisoning more people can even increase crime.I attempt here to briefly solve the puzzle, suggesting how the studies conflicting findings might be reconciled. The differences in the studies’ results may be due to the different characteristics of the periods that the studies address. The earlier studies examined periods when prison populations tended to grow by adding additional violent and property offenders. The studies’ empirical results supported what theory would seem unambiguously to suggest: that putting more offenders in prison should decrease crime by both incapacitating incarcerated offenders and deterring potential offenders. In contrast, during the periods that the later studies addressed, both the War on Drugs and new sentencing reforms caused prison populations to grow in two additional and different ways: by adding drug offenders and by increasing sentence lengths for low-level offenders. I discuss several reasons why imprisoning more drug offenders may not reduce crime and may even increase it. I also evaluate how longer sentences for low-level offenders may have similar, counterproductive effects. Finally, I explore how recent increases both in the numbers of drug offenders and in sentence lengths for low-level offenders might reconcile the studies’ results.

This study explores the impact of truth-in-sentencing (TIS) legislation on police, prosecutors, and criminals. Truth-in-sentencing laws are determinate-sentencing laws that require violent offenders to serve at least 85 percent of their prison sentences. The standard economic model of crime suggests that TIS laws will deter violent offenders but also reduce probabilities of arrest and conviction. However, I explain that if states share the goals of TIS legislation, police and prosecutors may increase these probabilities. My theoretical model also predicts that the legislation will cause more trials and impose higher maximum prison sentences. Using a county-level data set, empirical results confirm that TIS laws deter violent offenders, increase the probability of arrest, and increase maximum imposed prison sentences. Truth-in-sentencing laws decrease murders by 16 percent, aggravated assaults by 12 percent, robberies by 24 percent, rapes by 12 percent, and larcenies by 3 percent. However, offenders substitute into property crimes: burglaries increase by 20 percent and auto thefts by 15 percent. Copyright 2002 by the University of Chicago.

Many states have recently enacted three-strikes laws to increase punishment for frequent offenders. However, only California actively enforces its three-strikes legislation. Existing studies of the impact on crime in California consider only partial deterrence: the deterrence of offenders committing their last strike. The only study addressing full deterrence, the deterrence of all potential offenders, examines the impact across all states in a model that does not consider the simultaneity of crime and the passage of three-strikes laws. I offer a theoretical model that shows that strike laws should deter all offenders and that partial deterrence measurements underestimate the laws' benefits. Theory-based empirical results indicate that strike sentences generally deter the crimes covered by the laws. During the first 2 years of the legislation, approximately eight murders, 3,952 aggravated assaults, 10,672 robberies, and 384,488 burglaries were deterred in California; however, larcenies increased by 17,700 during this period. Copyright 2002 by the University of Chicago.

Despite a rapid increase in economic significance and substantial increase in international use, third-party litigation financing remains poorly understood. No academic consensus takes account of the multiple economic conundrums that third-party litigation financing arises to solve, nor do legal scholars adequately consider obvious public and private substitutes for litigation financing that society rightfully recognizes as innocuous or outright beneficial. In this Article, we explore the economic challenges driving both business plaintiffs and sophisticated law firms to seek external litigation financing. We examine closely the key elements of the litigation financing arrangement itself, focusing on eligible cases and clients, devices financiers employ to ensure repayment without meaningful control over the litigation, and theorize conditions under which third-party litigation financing will be attractive to companies and firms. We then address several concerns regarding third-party litigation financing, ultimately finding them either unpersuasive in theory or undemonstrated in fact. We conclude by noting the variety of similar arrangements already safely beyond the scope of these concerns. Ultimately, litigation financing encourages both businesses and firms to make more efficient uses of capital. Any attempt to regulate or dissuade litigation financing must begin with an economically and legally sound appreciation for how the industry actually functions.

Heat shock or stress proteins (Hsp) are typically regarded as being intracellular proteins that have a range of functions including the maintenance of cellular integrity. Members of the Hsp70 family of molecules have been implicated in the processing and presentation of antigen and the cross reactivity of lymphocytes specific for pathogen-derived heat shock proteins with self Hsp70 has been suggested to be an underlying cause of certain autoimmune diseases. This study reports the presence of soluble Hsp70 in the peripheral circulation of normal individuals. Concentrations of soluble Hsp70 in females were approximately twice those in males. Circulating anti-Hsp70 antibodies were detected in all individuals assessed, but there were no differences between males and females. However, there was a significant correlation between soluble Hsp70 concentration and antibody levels in males, but not females. The physiological role for circulating heat shock proteins is intriguing, but currently unknown. These findings extend our previous observations that Hsp60 is present in the peripheral circulation and support the proposition that soluble heat shock proteins may play a regulatory role in either the prevention or protection of pathophysiological processes involving inadvertent immunorecognition or cross-recognition of heat shock proteins.

This chapter summarizes the literature on the economic analysis of criminal law. First, it discusses the positive theory of criminal behavior and reviews the empirical evidence in support of the theory. Then, it discusses the normative theory of how public law enforcement should be designed to minimize the social costs of crime.