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We present a study case where the theory of sampling (TOS) is used to make defensible inferences in a nuclear forensic investigation. The forensic investigations focused on five suspicious radioactive materials seized in 2019. All errors introduced by sampling and sub-sampling the radioactive materials are evaluated according to TOS. A maximum sampling error of 35% was tolerated. The uses of TOS enabled the forensic team to make inferences about the seized materials and therefore make confidence-based statements about the exceeding of limits established in the Swiss Radiological Protection Ordinance for radioactive substances. The analysis of the isotope and activity ratios allowed the team to exclude some potential sources of the radioactive contamination; however, it was not possible to determine its origin precisely., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Copper nitrite reductases (CuNIRs) convert NO 2 - to NO as well as NO to N 2 O under high NO flux at a mononuclear type 2 Cu center. While model complexes illustrate N-N coupling from NO that results in symmetric trans -hyponitrite [Cu II ]-ONNO-[Cu II M (M = Co, Fe) to give the first copper 2 M (M = Co, Fe) to give the first copper cis M]{[Cu 2 M]{[Cu II ](κ 2 -O 2 N 2 )[Cu I ]}. Importantly, the κ 1 -N-bound [Cu I ] fragment may be easily removed by the addition of mild Lewis bases such as CNAr or pyridine to form the spectroscopically similar anion {[Cu II ](κ 2 -O 2 N 2 )} - . The addition of electrophiles such as H + to these anionic copper(II) cis -hyponitrites leads to N 2 O generation with the formation of the dicopper(II)-bis-μ-hydroxide [Cu II ] 2 (μ-OH) 2 . One-electron oxidation of the {[Cu II ](κ 2 -O 2 N 2 )} - core turns on H-atom transfer reactivity, enabling the oxidation of 9,10-dihydroanthracene to anthracene with concomitant formation of N 2 O and [Cu II ] 2 (μ-OH) 2 . These studies illustrate both the reductive coupling of NO at a single copper center and a way to harness the strong oxidizing power of nitric oxide via the neutral cis- hyponitrite [Cu](κ 2 -O 2 N 2 ).

Inhibitors for membrane transporters have been shown to be indispensable as drugs and tool compounds. The proton-dependent oligopeptide transporters PEPT1 and PEPT2 from the SLC15 family play important roles in human and mammalian physiology. With Lys[Z(NO 2 )]-Val (LZNV), a modified Lys-Val dipeptide, a potent transport inhibitor for PEPT1 and PEPT2 is available. Here we present the crystal structure of the peptide transporter YePEPT in complex with LZNV. The structure revealed the molecular interactions for inhibitor binding and a previously undescribed mostly hydrophobic pocket, the PZ pocket, involved in interaction with LZNV. Comparison with a here determined ligand-free structure of the transporter unveiled that the initially absent PZ pocket emerges through conformational changes upon inhibitor binding. The provided biochemical and structural information constitutes an important framework for the mechanistic understanding of inhibitor binding and action in proton-dependent oligopeptide transporters., (© 2022. The Author(s).)

The Bikar and Bokak Atolls, located in the northern Marshall Islands, are extremely isolated and consist of pristine marine and terrestrial ecosystems. Both atolls may have experienced significant radioactive deposition following the nuclear weapon testing conducted at Bikini and Enewetak proving grounds. Here we report activity concentrations of artificial radionuclides ( 239 Pu, 240 Pu, 241 Pu, 241 Am, 137 Cs and 90 Sr) in marine and terrestrial samples collected from Bikar and Bokak Atolls. Artificial radionuclides in soil from the Majuro Atoll are also reported and form a radiological baseline against which the levels at the other atolls can be compared. We observed low levels of artificial radionuclides in soil from Majuro and Bokak, but significantly higher levels in soil from Bikar. The residual radioactivity in the Bikar environment is comparable to the levels previously reported for other nearby atolls, including Taka and Utrik, but lower than for Rongerik, Rongelap, Bikini and Enewetak. An analysis of 240 Pu/ 239 Pu isotope ratios and estimations of the dates of contamination from 241 Am/ 241 Pu activity ratios both indicated that the Bikar Atoll was contaminated mainly by radioactive fallout from the Castle Bravo test in 1954. We compare the results of our measurements at Bikar and Bokak to data from other atolls in the Marshall Islands and to regions of the world affected by both global and regional fallout from atmospheric nuclear weapons testing and nuclear accidents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nitric oxide (NO) is a key signaling molecule in health and disease. While nitrite acts as a reservoir of NO activity, mechanisms for NO release require further understanding. A series of electronically varied β-diketiminatocopper(II) nitrite complexes [Cu II ](κ 2 -O 2 N) react with a range of electronically tuned triarylphosphines PAr Z 3 that release NO with the formation of O═PAr Z 3 . Second-order rate constants are largest for electron-poor copper(II) nitrite and electron-rich phosphine pairs. Computational analysis reveals a transition-state structure energetically matched with experimentally determined activation barriers. The production of NO follows a pathway that involves nitrite isomerization at Cu II from κ 2 -O 2 N to κ 1 -NO 2 followed by O-atom transfer (OAT) to form O═PAr Z 3 and [Cu I ]-NO that releases NO upon PAr Z 3 binding at Cu I to form [Cu I ]-PAr Z 3 . These findings illustrate important mechanistic considerations involved in NO formation from nitrite via OAT.

Novel approaches in synthetic biology focus on the bottom-up modular assembly of natural, modified natural or artificial components into molecular systems with functionalities not found in nature. A possible application for such techniques is the bioremediation of natural water sources contaminated with small organic molecules (e.g., drugs and pesticides). A simple molecular system to actively accumulate and degrade pollutants could be a bionanoreactor composed of a liposome or polymersome scaffold combined with energizing- (e.g., light-driven proton pump), transporting- (e.g., proton-driven transporter) and degrading modules (e.g., enzyme). This work focuses on the engineering of a transport module specific for β-lactam antibiotics. We previously solved the crystal structure of a bacterial peptide transporter, which allowed us to improve the affinity for certain β-lactam antibiotics using structure-based mutagenesis combined with a bacterial uptake assay. We were able to identify specific mutations, which enhanced the affinity of the transporter for antibiotics containing certain structural features. Screening of potential compounds allowed for the identification of a β-lactam antibiotic ligand with relatively high affinity. Transport of antibiotics was evaluated using a solid-supported membrane electrophysiology assay. In summary, we have engineered a proton-driven β-lactam antibiotic translocation module, contributing to the growing toolset for bionanotechnological applications., (© 2021. The Author(s).)

The current global systemic crisis reveals how globalised societies are unprepared to face a pandemic. Beyond the dramatic loss of human life, the COVID-19 pandemic has triggered widespread disturbances in health, social, economic, environmental and governance systems in many countries across the world. Resilience describes the capacities of natural and human systems to prevent, react to and recover from shocks. Societal resilience to the current COVID-19 pandemic relates to the ability of societies in maintaining their core functions while minimising the impact of the pandemic and other societal effects. Drawing on the emerging evidence about resilience in health, social, economic, environmental and governance systems, this paper delineates a multisystemic understanding of societal resilience to COVID-19. Such an understanding provides the foundation for an integrated approach to build societal resilience to current and future pandemics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The light-driven proton pump bacteriorhodopsin (BR) from the extreme halophilic archaeon Halobacterium salinarum is a retinal-binding protein, which forms highly ordered and thermally stable 2D crystals in native membranes (termed purple membranes). BR and purple membranes (PMs) have been and are still being intensively studied by numerous researchers from different scientific disciplines. Furthermore, PMs are being successfully used in new, emerging technologies such as bioelectronics and bionanotechnology. Most published studies used the wild-type form of BR, because of the intrinsic difficulty to produce genetically modified versions in purple membranes homologously. However, modification and engineering is crucial for studies in basic research and, in particular, to tailor BR for specific applications in applied sciences. We present an extensive and detailed protocol ranging from the genetic modification and cultivation of H. salinarum to the isolation, and biochemical, biophysical and functional characterization of BR and purple membranes. Pitfalls and problems of the homologous expression of BR versions in H. salinarum are discussed and possible solutions presented. The protocol is intended to facilitate the access to genetically modified BR versions for researchers of different scientific disciplines, thus increasing the application of this versatile biomaterial.

This retrospective study evaluated the outcome after intramedullary nailing with the Rockwood Clavicle Pin (RCP) for acute displaced middle third clavicle fractures in adults. Of 84 included patients treated for this fracture 2003-2009, 66 (79%) were evaluated. Of these, 52 (79%) were re-examined, including fluoroscopy, while 14 patients (21%) were evaluated by mailed questionnaire. Primary outcome was Constant score (CS), secondary outcomes included : Subjective Shoulder Value (SSV), healing rate at follow up, complications, and cosmetic appearance. Patients were re-evaluated with a mean follow-up of 39 months (range 13-96). Mean CS at follow up was 90 (range 55-100) and mean shoulder function measured with the SSV was 93 (range 36-100). Three (6%) of the re-examined patients had a non-union at follow up. Twelve (18%) had wound problems, with exposure of the lateral part of the pin in five patients (8%). There were no deep infections but seven patients (11%) were treated for superficial wound infections. Breakage of the implant occurred in one case (2%). Treatment of displaced midshaft clavicle fractures with the RCP results in good clinical outcome and a high patient satisfaction with a high healing rate. However, the technique is associated with postoperative complications. Level of evidence : Level IV, Case series with no comparison group. Treatment study.

Background: Regular infant carrying might be a contributing factor for the development and progression of low back and pelvic girdle pain in mothers after childbirth. However, the neuromechanical adaptations of the spine due to different sling-based carrying techniques are not sufficiently well understood in order to provide evidence-based carrying recommendations., Research Question: What are the immediate effects of different sling-based infant carrying techniques on trunk neuromechanics?, Methods: Using a Vicon motion capture and a wireless surface electromyography system, three-dimensional pelvis and spinal kinematics as well as activation patterns of eight trunk muscles were derived from fifteen healthy young women during upright standing and level walking without carrying a load and while carrying a 6 kg-dummy with a sling in front and on either side. Data were analyzed using Statistical Parametric Mapping, allowing group comparisons of discrete parameters (standing) as well as continuous data (walking). To distinguish between clinically relevant and clinically not relevant kinematic findings, statistically significant differences were only considered in case of ≥5°., Results: Compared to unloaded walking, carrying the dummy in front was mainly associated with increased lumbar lordosis (standing: (Δ8.8°, p = 0.006; walking: (Δ ≥ 8.2°, 1-100% of gait cycle [%GC], p < 0.001). When carrying the dummy on the preferred side, increased thoracic kyphosis (standing: ≥6.4°, p ≤ 0.003; walking: Δ ≥ 5.6°, 1-100%GC, p < 0.001) and axial rotation towards the ipsilateral side (standing: Δ5.3°, p = 0.003; walking: Δ ≥ 5.0°, 46-58%GC, p = 0.002) were observed. All three conditions entailed increased paraspinal muscle activity during walking, although only unilaterally in side carrying (lumbar, preferred condition: Δ ≥ 13.2%maxMVIC, 49-57%GC, p < 0.001; thoracic, non-preferred condition: Δ ≥ 5.3%maxMVIC, 47-58%GC, p < 0.001)., Significance: Carrying an infant alternating on both sides using a sling could be advantageous for preventing musculoskeletal pain resulting from excessive lumbar hyperextension and paraspinal muscle hyperactivation in women after childbirth., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

To understand how membrane proteins function requires characterizing their structure, assembly, and inter- and intramolecular interactions in physiologically relevant conditions. Conventionally, such multiparametric insight is revealed by applying different biophysical methods. Here we introduce the combination of confocal microscopy, force-distance curve-based (FD-based) atomic force microscopy (AFM), and single-molecule force spectroscopy (SMFS) for the identification of native membranes and the subsequent multiparametric analysis of their membrane proteins. As a well-studied model system, we use native purple membrane from Halobacterium salinarum, whose membrane protein bacteriorhodopsin was His-tagged to bind nitrilotriacetate (NTA) ligands. First, by confocal microscopy we localize the extracellular and cytoplasmic surfaces of purple membrane. Then, we apply AFM to image single bacteriorhodopsins approaching sub-nanometer resolution. Afterwards, the binding of NTA ligands to bacteriorhodopsins is localized and quantified by FD-based AFM. Finally, we apply AFM-based SMFS to characterize the (un)folding of the membrane protein and to structurally map inter- and intramolecular interactions. The multimethodological approach is generally applicable to characterize biological membranes and membrane proteins at physiologically relevant conditions.

Western corn rootworm (WCR), Diabrotica virgifera virgifera, is one of the most significant pests of corn in the United States. Although transgenic solutions exist, increasing resistance concerns make the discovery of novel solutions essential. In order to find a novel protein with high activity and a new mode of action, a large microbial collection was surveyed for toxicity to WCR using in vitro bioassays. Cultures of strain ATX2024, identified as Chromobacterium piscinae, had very high activity against WCR larvae. The biological activity from the strain was purified using chromatographic techniques and fractions were tested against WCR larvae. Proteins in the final active fraction were identified by mass spectrometry and N-terminal sequencing and matched to the genome of ATX2024. A novel 58.9kDa protein, identified by this approach, was expressed in a recombinant expression system and found to have specific activity against WCR. Transgenic corn events containing this gene showed good protection against root damage by WCR, with average scores ranging between 0.01 and 0.04 on the Iowa State node injury scale. Sequence analysis did not reveal homology to any known insecticidal toxin, suggesting that this protein may act in a novel way to control WCR. The new WCR active protein is named GNIP1Aa, for Gram Negative Insecticidal Protein., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Synthetic biology approaches range from the introduction of unique features into organisms to the assembly of isolated biomacromolecules or synthetic building blocks into artificial biological systems with biomimetic or completely novel functionalities. Simple molecular systems can be based on containers on the nanoscale that are equipped with tailored functional modules for various applications in healthcare, industry or biological and medical research. The concept, or vision, of assembling native or engineered proteins and/or synthetic components as functional modules into molecular systems is discussed. The main focus is laid on the engineering of energizing modules generating chemical energy, transport modules using this energy to translocate molecules between compartments of a molecular system, and catalytic modules (bio-)chemically processing the molecules. Further key aspects of this discourse are possible approaches for the assembly of simple nanofactories and their applications in biotechnology and medical health.

Phosphate remobilization from digested sewage sludge containing iron phosphate was scaled-up in a microbial fuel cell (MFC). A 3litre triple chambered MFC was constructed. This reactor was operated as a microbial fuel cell and later as a microbial electrolysis cell to accelerate cathodic phosphate remobilization. Applying an additional voltage and exceeding native MFC power accelerated chemical base formation and the related phosphate remobilization rate. The electrolysis approach was extended using a platinum-RVC cathode. The pH rose to 12.6 and phosphate was recovered by 67% in 26h. This was significantly faster than using microbial fuel cell conditions. Shrinking core modelling particle fluid kinetics showed that the reaction resistance has to move inside the sewage sludge particle for considerable rate enhancement. Remobilized phosphate was subsequently precipitated as struvite and inductively coupled plasma mass spectrometry indicated low levels of cadmium, lead, and other metals as required by law for recycling fertilizers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Human heteromeric amino acid transporters (HATs) are membrane protein complexes that facilitate the transport of specific amino acids across cell membranes. Loss of function or overexpression of these transporters is implicated in several human diseases such as renal aminoacidurias and cancer. HATs are composed of two subunits, a heavy and a light subunit, that are covalently connected by a disulphide bridge. Light subunits catalyse amino acid transport and consist of twelve transmembrane α-helix domains. Heavy subunits are type II membrane N-glycoproteins with a large extracellular domain and are involved in the trafficking of the complex to the plasma membrane. Structural information on HATs is scarce because of the difficulty in heterologous overexpression. Recently, we had a major breakthrough with the overexpression of a recombinant HAT, 4F2hc-LAT2, in the methylotrophic yeast Pichia pastoris. Microgram amounts of purified protein made possible the reconstruction of the first 3D map of a human HAT by negative-stain transmission electron microscopy. Here we report the important stabilization of purified human 4F2hc-LAT2 using a combination of two detergents, i.e., n-dodecyl-β-D-maltopyranoside and lauryl maltose neopentyl glycol, and cholesteryl hemisuccinate. The superior quality and stability of purified 4F2hc-LAT2 allowed the measurement of substrate binding by scintillation proximity assay. In addition, an improved 3D map of this HAT could be obtained. The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution, and thus the elucidation of the working mechanism of this important protein complex at the molecular level.

Publicly available scientific resources help establish evaluation standards, provide a platform for teaching and improve reproducibility. Version 4 of the Insight ToolKit (ITK(4)) seeks to establish new standards in publicly available image registration methodology. ITK(4) makes several advances in comparison to previous versions of ITK. ITK(4) supports both multivariate images and objective functions; it also unifies high-dimensional (deformation field) and low-dimensional (affine) transformations with metrics that are reusable across transform types and with composite transforms that allow arbitrary series of geometric mappings to be chained together seamlessly. Metrics and optimizers take advantage of multi-core resources, when available. Furthermore, ITK(4) reduces the parameter optimization burden via principled heuristics that automatically set scaling across disparate parameter types (rotations vs. translations). A related approach also constrains steps sizes for gradient-based optimizers. The result is that tuning for different metrics and/or image pairs is rarely necessary allowing the researcher to more easily focus on design/comparison of registration strategies. In total, the ITK(4) contribution is intended as a structure to support reproducible research practices, will provide a more extensive foundation against which to evaluate new work in image registration and also enable application level programmers a broad suite of tools on which to build. Finally, we contextualize this work with a reference registration evaluation study with application to pediatric brain labeling.

Working memory is important for mental reasoning and learning processes. Several studies in adults and school-age children have shown performance improvement in cognitive tests after working memory training. Our aim was to examine not only immediate but also long-term effects of intensive working memory training on cognitive performance tests in children. Fourteen healthy male subjects between 10 and 16 years trained a visuospatial n-back task over 3 weeks (30 min daily), while 15 individuals of the same age range served as a passive control group. Significant differences in immediate (after 3 weeks of training) and long-term effects (after 2-6 months) in an auditory n-back task were observed compared to controls (2.5 fold immediate and 4.7 fold long-term increase in the training group compared to the controls). The improvement was more pronounced in subjects who improved their performance during the training. Other cognitive functions (matrices test and Stroop task) did not change when comparing the training group to the control group. We conclude that visuospatial working memory training in children boosts performance in similar memory tasks such as the auditory n-back task. The sustained performance improvement several months after the training supports the effectiveness of the training.

The Cancer Support Community (CSC) provides psychosocial support to people facing cancer in community settings. The purpose of this study was to evaluate the compatibility, effectiveness, and fidelity of the Situation-Choices-Objectives-People-Evaluation-Decisions (SCOPED) question-listing intervention at three CSC sites. Between August 2008 and August 2011, the Program Director at each CSC site implemented question-listing, while measuring patient distress, anxiety, and self-efficacy before and after each intervention. We analyzed the quantitative results using unadjusted statistical tests and reviewed qualitative comments by patients and the case notes of Program Directors to assess compatibility and fidelity. Program Directors implemented question-listing with 77 blood cancer patients. Patients reported decreased distress (p = 0.009) and anxiety (p = 0.005) and increased self-efficacy (p < 0.001). Patients and Program Directors endorsed the intervention as compatible with CSC's mission and approach and feasible to implement with high fidelity. CSC effectively translated SCOPED question-listing into practice in the context of its community-based psychosocial support services at three sites.

Plasma catecholamines provide a reliable biomarker of sympathetic activity. The low circulating concentrations of catecholamines and analytical interferences require tedious sample preparation and long chromatographic runs to ensure their accurate quantification by HPLC with electrochemical detection. Published or commercially available methods relying on solid phase extraction technology lack sensitivity or require derivatization of catecholamine by hazardous reagents prior to tandem mass spectrometry (MS) analysis. Here, we manufactured a novel 96-well microplate device specifically designed to extract plasma catecholamines prior to their quantification by a new and highly sensitive ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Processing time, which included sample purification on activated aluminum oxide and elution, is less than 1 h per 96-well microplate. The UPLC-MS/MS analysis run time is 2.0 min per sample. This UPLC-MS/MS method does not require a derivatization step, reduces the turnaround time by 10-fold compared to conventional methods used for routine application, and allows catecholamine quantification in reduced plasma sample volumes (50-250 μL, e.g., from children and mice).

It is shown how the newly developed technique of magneto-optical-trap recoil-ion momentum spectroscopy can be used to measure the temporal evolution of excited state fraction in such a trap. In this case, the fraction of atoms in a 5p state is measured. The technique can be generalized to allow the measurement of more complicated systems, e.g., a Rb sample having a mixture of 5s, 5p, 4d, and Rydberg states.

To facilitate evaluation of enzyme-ligand complexes in solution, we have isolated the 26-kDa N-terminal domain of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase for analysis by NMR spectroscopy. The isolated domain is capable of binding the substrate shikimate-3-phosphate (S3P), and this letter reports the localization of the S3P binding site using chemical shift mapping. Based on the NMR data, we propose that Ser23, Arg27, Ser197, and Tyr200 are directly involved in S3P binding. We also describe changes in the observed nuclear Overhauser effects (NOEs) that are consistent with a partial conformational change in the N-terminal domain upon S3P binding.

5-Enolpyruvylshikimate-3-phosphate (EPSP) synthase catalyzes the transfer of the enolpyruvyl moiety from phosphoenolpyruvate (PEP) to shikimate-3-phosphate (S3P). Mutagenesis and X-ray crystallography data suggest that the active site of the enzyme is in the cleft between its two globular domains; however, they have not defined which residues are responsible for substrate binding and catalysis. Here we attempt to establish the binding of the substrate S3P to the isolated N-terminal domain of EPSP synthase using a combination of NMR spectroscopy and isothermal titration calorimetry. Our experimental results indicate that there is a saturable and stable conformational change in the isolated N-terminal domain upon S3P binding and that the chemical environment of the S3P phosphorus when bound to the isolated domain is very similar to that of S3P bound to EPSP synthase. We also conclude that most of the free energy of S3P binding to EPSP synthase is contributed by the N-terminal domain.

Following efforts to ban the use of gag clauses, state lawmakers now are turning their attention to prohibiting managed care plans from using financial incentives. Twenty-seven states have enacted laws banning the use of such incentives.

Forty-eight states prohibit managed care organizations (MCOs) from limiting a provider's ability to discuss potential treatment options with patients.

When a health care provider disenrolls or is terminated by a managed care plan, how long can that provider's patients continue to receive covered treatment for a life-threatening condition, pregnancy, disability or other circumstance that requires continuous medical care? Lawmakers in twenty-seven states have answered that question.

Should managed care plans have the ability to limit an individual's "freedom of choice" when it comes to selecting a provider? As part of the anti-managed care movement of the early 1990s, 22 states enacted freedom of choice laws; the majority apply only to pharmacies.

Today, almost half the states have laws obligating managed care organizations (MCOs) such as health maintenance organizations (HMOs) and preferred provider organizations (PPOs) to contract with any willing health care provider. Although most provisions are limited to pharmacies or pharmacists, several states have adopted broad provisions applying to hospitals, physicians, chiropractors, pharmacists, podiatrists, therapists and nurses.

Medical directors of managed care organizations have the ultimate responsibility of deciding the treatments for which a health plan will pay. Cognizant of consumer concerns over the power inherent in the position, states are seeking to inject more accountability into the decision-making process. Among the issues with which they have begun to grapple: whether medical directors should be required to hold a medical license from the state in which they work and, by extension, whether they should be under the jurisdiction of the state medical board.

When a health plan denies payment for a procedure on grounds that it is not medically necessary or when it refuses a physician-ordered referral to a specialist, has it crossed the line from making an insurance judgment to practicing medicine? If the patient suffers harm as a result of the decision, is the plan liable for medical malpractice? Those were questions 35 states considered in 1999, and at least 32 states are grappling with this year as they seek to respond to physician and patient pressure to curb the power of the managed care industry. Traditionally, health insurers have been protected by state laws banning "the corporate practice of medicine," which means the patient's only recourse is to sue under a "vicarious liability" theory. Now, however, lawmakers are debating legislation to extend the scope of malpractice liability beyond individual practitioners to insurance carriers and plans themselves.

Although under standard business laws withholding prompt payment is considered an unfair trade practice, a number of states are enacting new laws or clarifying existing language to ensure that health plans are paying providers in a timely fashion.

State lawmakers across the country have begun to play an important role in ensuring that managed care plans establish and maintain grievance and appeals procedures that are responsive to the needs of their constituents.

A point-of-service (POS) option is a type of plan offered by managed care organizations (MCOs), including health maintenance organizations (HMOs), that allows people who are willing to pay higher out-of-pocket costs to see out-of-plan providers. Mandating a point-of-service option essentially eliminates the use of closed-panel HMOs. This issue brief addresses only bills that mandate managed care plans to offer a point-of-service option.

State lawmakers are aggressively enacting legislation that--depending on the perspective--either regulates managed care or provides for consumer protections. More than half the states have adopted a "Patient Bill of Rights." These new laws address the entire range of managed care issues, including, but not limited to, provider access, bans on gag clauses, consumer grievance procedures, direct access, disclosure, provider credentialing, medical records, insurer liability, solvency, drug formularies, certification and, in some cases, a point-of-service option.

Under what circumstances is an enrollee in a managed care plan eligible to exercise judgment as a "prudent layperson" in determining that an emergency medical condition exists? Does his or her condition justify immediate attention without prior authorization, even if it means an emergency room visit or dialing 911?

From pregnancy to breast cancer screening and osteoporosis prevention, women have a need for a gender-specific set of health services. Dialogue that once occurred only between women and their physicians has evolved into debate between representatives from the insurance industry and state legislators. Therefore, women's health issues have risen on the legislative agenda, illustrated by the increased volume of bills introduced and enacted during the past five years.

While national efforts are aimed at strengthening consumer protections under managed care, a number of states are increasing efforts to improve protections for providers as well. Written notification of contract termination, ensuring the existence of a due process, and disclosure of credentialing criteria are three options states are pursuing.

The information in this Issue Brief is based on a 50-state survey and a recent literature review. The Health Policy Tracking Service recognizes the complexity of this issue and discourages anyone from using this as their sole resource on the issue.

Although historically direct access legislation has focused on OB/GYNs, lawmakers are attempting to extend that "right" to other health care professionals. Although the bills address the familiar provider groups--dermatologist, eye care providers and chiropractors--an even greater number of bills address the use of specialists as primary care providers.

Group psychotherapy for children with chronic medical illness can be a powerful tool in facilitating their social and emotional adjustment to their condition. In this article, the author addresses the theoretical issues in developing and managing such a group, drawing on his experience with a long-term psychotherapy group of four children of varying ages and medical conditions. Themes arising from this group included universality of experience, understanding the disabilities of others, sharing, relationships with parents, and grief and loss. In addition to addressing developmental tasks of individual group members, the author presents therapist-related issues (e.g., transference, countertransference, the cotherapy relationship, and the therapist-parent relationship). The author concludes that participation in an ongoing psychotherapy group can provide medically ill children with considerable opportunity for growth, understanding, meaning, and adaptation.

There is evidence that prolactin (PRL) excess plays a role in the etiology of osteoporosis associated with human prolactinoma. Calcium balance in human hyperprolactinemia has not been thoroughly investigated. In the present study, rats with excess circulating PRL levels (male anterior pituitary-grafted Fischer 344 rats) had urinary calcium excretion twice that of control rats (4.16 +/- 0.43 v 2.25 +/- 0.30 mg/24h X 100 g BW). Calcium excretion expressed per mg of calcium intake was also high in pituitary-grafted rats. The excess calcium excretion in hyperprolactinemic rats was not accompanied by a concomitant rise in sodium excretion. This dissociation suggests that PRL has an effect on the renal handling of calcium. Since thiazide diuretics have a well-described hypocalciuric action, their effect was tested in these rats. In normal rats, benzthiazide, a long-acting agent, significantly reduced urinary calcium excretion in a dose-dependent fashion. Hyperprolactinemic rats responded to benzthiazide in a manner similar to control rats. In pituitary-grafted rats, benzthiazide also decreased the calcium excretion to intake ratio and normalized the calcium to sodium excretion ratio. Since the hypercalciuria of experimental hyperprolactinemia can be corrected by thiazide diuretics, these agents may have therapeutic potential in human PRL excess.

Many previous studies have established the value of the autopsy in assessing clinical diagnostic accuracy. None has described, however, the use of the autopsy as an ongoing, prospective audit of clinical and pathologic performance. The authors herein outline the process and report the initial results of a comprehensive quality assessment program on their autopsy service. Particular emphasis was placed on evaluation of the responsiveness of the autopsy to clinical questions and interests. The four parts of the overall program included an epidemiologic survey of causes of death in the authors' patient population, a determination of the clinical significance of autopsy findings, an assessment of clinical factors that may have contributed to death, and a quality control mechanism of the autopsy itself. The process can be adapted to a variety of hospital settings.

Twenty normal-hearing subjects were tested to determine their speech reception thresholds (SRTs) using the Tillman-Olsen method and a modification of their method requiring no knowledge of the pure-tone audiogram from which to estimate the SRT. Varying amounts of attenuation were added to the line leading to the test earphone to minimize experimenter bias. The data revealed no significant differences between the two methods in either the SRTs themselves or the amount of time required to obtain them. A procedure is therefore advanced for clinicians wishing to measure SRTs without prior knowledge of pure-tone thresholds.