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NRG Oncology's Developmental Therapeutics and Radiation Therapy Subcommittee assembled an interdisciplinary group of investigators to address barriers to successful early phase clinical trials of novel combination therapies involving radiation. This Policy Review elucidates some of the many challenges associated with study design for early phase trials combining radiotherapy with novel systemic agents, which are distinct from drug-drug combination development and are often overlooked. We also advocate for potential solutions that could mitigate or eliminate some of these barriers, providing examples of specific clinical trial designs that could help facilitate efficient and effective evaluation of novel drug-radiotherapy combinations., Competing Interests: Declaration of interests JMB received grants or contracts from the National Institutes of Health (NIH); royalties or licences from UpToDate; and has a leadership or fiduciary role in other board, society, committee, or advocacy group (paid or unpaid) for the American Society for Radiation Oncology (ASTRO) and is on the Board of Directors as Science Council Chair. SEF reports ongoing research with Novartis and Bayer; received consulting fees from Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; payment or honoraria as a speaker for Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; participates on an advisory board at Lantheas, Progenics, Blue Earth, Bayer, Astellas, Pfizer, and Jaansen; and has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid on the board of chancellors at the American College of Radiology. SKJ received grants or contracts from the National Cancer Institute, Merck, Beigene, Guardant, and Adlai made to their institution; consulting fees from Merck, AstraZeneca, Beigene, Radialogica, Syntactx, and IMX; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from ASTRO; is a senior editor at the International Journal of Radiation Biology Physics; received payment for expert testimony from Dechert; support for attending meetings and travel from ASTRO, AstraZeneca, and Merck; and participation on a data safety monitoring board for Advarra. RJK declares ongoing committee role at ASTRO and ongoing senior editor role at International Journal of Radiation Oncology Biology Physics; received grants or contracts from NIH and Bridge Bio to their institution; received consulting fees from HunaTek and Guidepoint Global; has patents planned, issued, or pending with University of Wisconsin; and has leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid with ASTRO. SHL received grants from Beyond Spring, STCube Pharmaceuticals, and Nektar Therapeutics; consulting fees from XRAD Therapeutics; support for attending meetings and travel from AstraZeneca; participated on an advisory board for AstraZeneca and Creatv Microtech; and has stock or stock options from Seek Diagnostics. AMM received consulting fees from AstraZeneca, Merck, Varian Medical Systems, Kortuc, and Siemens; payment for expert testimony from Arizona Legal Group; support for attending meetings and travel from NRG Oncology; and has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at American Brachytherapy Society. JM declares in the last 36 months grants or contracts from NIH, Merck, BMS, Genentech, Incyte, Trisalus, Transgene, and EMD Serono; consulting fees from GLG and Guidepoint; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Association of Northern California Oncologists; participation on a data safety monitoring board or advisory board at Multiplex Thera; and stock or stock options from Multiplex Thera. SPP received grants or contracts from Amgen, AstraZeneca, MedImmune, A2bio, Bristol Myers Squibb, Eli Lilly, Fate Therapeutics, Gilead, Iovance, Merck, Pfizer, and Roche Genentech; and consulting fees from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Certis, Eli Lilly, Jazz, Genentech, Illumina, Merck, Pfizer, Signatera, and Tempus. SS received grants or contracts from Merck, Regeneron, Exelixis, and Innovio; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Exelixis and Medscape; and participated on a data safety monitoring board or advisory board at Luminos, Eisai, and Naveris. MX-W received grants or contracts from NCI; consulting fees from Eli Lilly and Novocure; and participated on a data safety monitoring board or advisory board for Eli Lilly. ZSZ has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid at the American Board of Radiology. KRP and PAT-S are employed by the NIH. TMW declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Common biologic samples used to diagnose COVID-19 include nasopharyngeal, nasal, or oropharyngeal swabs, and salivary samples. The performance characteristics of a sucked "lollipop" swab to detect SARS-CoV-2 virus is assessed in four small sub-studies., Methods: In each sub-study, a flocked swab was sucked for 20 s and submitted for PCR detection of SARS-CoV-2 virus., Results: Across all studies, 52 of 69 (75.4%) COVID-19 positive participants had positive "lollipop" swabs. Twelve of the 17 COVID-19 positive participants with negative "lollipop" swabs had known corresponding cycle threshold values of >37 from their nasal/nasopharyngeal swabs, an indication of low viral load at time of sampling. In a paired samples sub-study, the sensitivity and specificity of the "lollipop" swabs were 100% and 98%., Conclusions: "Lollipop" swabs performed satisfactorily especially in individuals with acute infection of COVID-19. "Lollipop" swabs are a simple method of sample collection for detecting SARS-CoV-2 virus and warrants additional consideration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shelby O'Connor reports financial support was provided by Wisconsin Partnership Program - AAJ7234 related to study materials. Ellen Wald reports financial support was provided by Wisconsin Partnership Program - AAJ7234 related to study materials. Shelby O'Connor reports a relationship with National Institutes of Health that includes: funding grants. Shelby O'Connor reports a relationship with Gingko Concentric that includes: funding grants. Shelby O'Connor reports a relationship with Centers for Disease Control and Prevention that includes: funding grants. Shelby O'Connor reports a relationship with Bill and Melinda Gates Foundation that includes: funding grants. Shelby O'Connor reports a relationship with AEGIS that includes: funding grants. Dr. Shelby has served as a reviewer for the Scientific Review Panel PREPARE (Program of Research in Epidemic Preparedness and Response). If there are other authors, they 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 © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

The enzyme 2-methylerythritol 2,4-cyclodiphosphate synthase, IspF, is essential for the biosynthesis of isoprenoids in most bacteria, some eukaryotic parasites, and the plastids of plant cells. The development of inhibitors that target IspF may lead to novel classes of anti-infective agents or herbicides. Enantiomers of tryptophan hydroxamate were synthesized and evaluated for binding to Burkholderia pseudomallei (Bp) IspF. The L-isomer possessed the highest potency, binding BpIspF with a K D of 36 µM and inhibited BpIspF activity 55% at 120 µM. The high-resolution crystal structure of the L-tryptophan hydroxamate (3)/BpIspF complex revealed a non-traditional mode of hydroxamate binding where the ligand interacts with the active site zinc ion through the primary amine. In addition, two hydrogen bonds are formed with active site groups, and the indole group is buried within the hydrophobic pocket composed of side chains from the 60 s/70 s loop. Along with the co-crystal structure, STD NMR studies suggest the methylene group and indole ring are potential positions for optimization to enhance binding potency., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Despite the growing interest in the experiences of transgender individuals, the phenomenon of fetishization of transgender bodies and identities has been overlooked. The present study was aimed at investigating the experiences of fetishization of transgender and nonbinary (TGNB) people. Participants in the current study represent a sample of 142 TGNB volunteers from the community who answered the prompt: "If you feel comfortable, could you describe your experience of being fetishized?" Using thematic analysis, we developed three overarching themes relevant to the experiences of fetishization of TGNB participants: (1) context of fetishization; (2) negative experiences of fetishization; and (3) positive or ambiguous experiences of fetishization. The results demonstrated that, in most cases, fetishization was understood by TGNB people as a negative experience of sexual objectification, although some individuals experienced fetishization as a positive experience, perceiving the sexual desire of the other person or living it as a kink. Consistent with the integrated theory of dehumanization, the results demonstrated that both sexual objectification and minority stress contributed to participants' understanding of fetishization for TGNB individuals. Implications for clinical work with TGNB individuals are discussed.

Background: Industry funding of research comes with important conflicts of interest, especially when research findings have financial implications for funders. When considering industry funding, academic investigators seek ways to mitigate and manage conflict to ensure integrity of research design, analysis, interpretation, and to protect researchers' and their institutions' credibility. This qualitative study's purpose was to conduct semi-structured interviews with expert stakeholders to gain insight into industry funding of research focused on nutrition and obesity, and determine the feasibility of developing a transparent process using an advisory board to help govern industry funding and manage conflict., Methods: We conducted seven semi-structured interviews with a purposive group of expert stakeholders representing varied perspectives. We distributed a summary of the advisory board concept to interviewees; developed and used a 16-question interview guide; and analyzed the interviews using open coding, manifest content analysis, axial coding, and code list reviews to identify and refine themes., Results: Most interviewees agreed that managing conflicts between industry funders and researchers was possible but difficult. They believed a carefully constructed advisory board empowered with specific responsibilities could help facilitate this process. They posited that strict guidelines are required to protect research quality and reporting, researcher(s)' and research institution(s)' reputations, and subsequent policy influenced by the research findings. They recommended specific guidelines and a framework for developing and administering the advisory board., Conclusions: A carefully constructed advisory board empowered with specific responsibilities could be useful to manage actual and perceived conflicts of interest, and increase transparency of research processes, funding, and results for industry-funded research. Stricter guidelines than those previously proposed in existing frameworks are needed to instill confidence in industry-funded nutrition and obesity research. A possible next step could include a pilot study of the advisory board concept to determine specific requirements for execution and to develop rigorous guidelines.

Objective: Angiogenesis inhibition is a valuable strategy for ovarian cancer (EOC). Pazopanib (paz) is a potent small molecular inhibitor of VEGF-1, -2, -3, PDGFR, c-kit, and has activity as a single agent in ovarian cancer. We designed a trial to assess the benefit of adding paz to gemcitabine (gem) in patients with recurrent EOC., Methods: An open-label, randomized, multi-site, phase 2 trial was conducted (NCT01610206) including patients with platinum resistant or sensitive disease, ≤ 3 prior lines of chemotherapy, and measurable/evaluable disease. Patients were randomly assigned to weekly gem 1000 mg/m 2 on days 1 and 8 of a 21 day cycle, with or without paz 800 mg QD, stratified by platinum sensitivity and number of prior lines (1 vs 2 or 3). The primary endpoint was PFS., Results: 148 patients were enrolled 2012-2017. Median age was 63 years (30-82); 60% were platinum resistant; median surveillance was 13 months (0.4-54 months). Median PFS was 5.3 (95% CI, 4.2-5.8) vs 2.9 months (95% CI, 2.1-4.1) in the gem arm. The PFS effect was most pronounced in the platinum resistant group (5.32 vs 2.33 months Tarone-Ware p < 0.001). There was no difference in OS. Overall RR (PR 20% vs 11%, Chi-squre p = 0.02) and DCR (80% vs 60%, Chi-square p < 0.001) were higher in the combination. High grade AEs in the combination arm included ≥ Grade 3: hypertension (15%), neutropenia (35%), and thrombocytopenia (12%)., Conclusions: The addition of paz to gem enhanced anti-tumor activity; those with platinum-resistant disease derived the most benefit from combination therapy, even in the setting of receiving prior bevacizumab., Competing Interests: Declaration of competing interest Dr. Duska has served on advisory boards for Astra Zeneca, Genentech, Merck, Tesaro, Morphotek. She serves on the DSMC for an Inovio trial. She has received research funding from GSK/Novartis (current trial) and Merck. Her instition has received research funding from multiple pharmaceutical companies. Dr. Secord reports research funding from pharmaceutical companies outside the submitted work; and a grant from the National Cancer Trial Network outside the submitted work. She also reports honoraria/advisory boards from Alexion, Aravive, Astex Pharmaceuticals Inc., Astra Zeneca, Clovis, Janssen/Johnson & Johnson, Merck, Mersana, Myriad, Oncoquest, Roche/Genentech, and Tesaro outside of the submitted work. Dr. Moore has served on advisory boards for Astra Zeneca, Advaxis, Clovis, Immunogen, Tesaro, Genentech/Roche, Janssen, Pfizer, Merck, Aravive, Samumed, Oncomed, VBL Therapeutics and Eisai. She serves on steering committees (not compensated) for Astra Zeneca, Tesaro, VBL Therapeutics. She has received research funding from PTC Therapeutics, Lilly, Genentech/Roche and Clovis. Dr. Brown reports personal fees from Tesaro, personal fees from Clovis, from Tempus, personal fees from AstraZeneca, personal fees from Genentech, personal fees from Olympus, personal fees from Advanced Surgical Concepts, personal fees from OncLive, outside the submitted work. The following authors report no financial interests: Dr. McGuire, Dr. Petroni, Ms Varhegyi, Dr. Barroilhet, Dr. Jelovac, Dr. Darus., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Scope: Increased fruit consumption is associated with reduced risk of colitis. It has been investigated whether the anti-colitic effects of the polyphenol-rich aronia berry (Aronia mitschurinii 'Viking') are mediated through Th17 and Treg., Methods and Results: Colitis is induced in recombinase activating gene-1 deficient mice injected with syngeneic CD4 + CD62L + naïve T cells. Mice consume either 4.5% w/w aronia-berry-supplemented or a control diet concurrent with T cell transfer. The extent of colitis and immunocyte populations are evaluated at weeks 3 to 7 after transfer. Aronia consumption prevents colitic wasting and reduces colon weight/length ratios relative to the control diet at weeks 5 and 7. Compared to the control diet, aronia feeding increases Treg in mesenteric lymph node at all colitis stages. Treg and regulatory Th17 subpopulations (IL-17A + IL-10 + and IL-17A + IL-22 + ) are increased in lamina propria and spleen at week 5 in aronia-fed mice. Aronia feeding also decreases total CD4 + cells but increases colonic Tregs. The ability of aronia to modulate colonic cytokines is associated with functional T cell IL-10 and increased diversity of microbiota., Conclusions: Aronia berry consumption inhibits adoptive transfer colitis by increasing Treg and regulatory Th17 cells. Dietary modulation of T cells is dynamic and precedes colitic wasting., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease that progresses to right ventricular (RV) failure and death if left untreated. Little is known regarding the progression of RV failure in this disease, greatly limiting effective prognoses, and therapeutic interventions. Large animal models enable the use of clinical techniques and technologies to assess progression and diagnose failure, but the existing large animal models of CTEPH have not been shown to replicate the functional consequences of the RV, i.e., RV failure. Here, we created a canine embolization model of CTEPH utilizing only microsphere injections, and we used a combination of right heart catheterization (RHC), echocardiography (echo), and magnetic resonance imaging (MRI) to quantify RV function. Over the course of several months, CTEPH led to a 6-fold increase in pulmonary vascular resistance (PVR) in four adult, male beagles. As evidenced by decreased cardiac index (0.12 ± 0.01 v. 0.07 ± 0.01 [L/(min * kg)]; p < 0.05), ejection fraction (0.48 ± 0.02 v. 0.31 ± 0.02; p < 0.05), and ventricular-vascular coupling ratio (0.95 ± 0.09 v. 0.45 ± 0.05; p < 0.05), as well as decreased tricuspid annular plane systolic excursion (TAPSE) (1.37 ± 0.06 v. 0.86 ± 0.05 [cm]; p < 0.05) and increased end-diastolic volume index (2.73 ± 0.06 v. 2.98 ± 0.02 [mL/kg]; p < 0.05), the model caused RV failure. The ability of this large animal CTEPH model to replicate the hemodynamic consequences of the human disease suggests that it could be utilized for future studies to gain insight into the pathophysiology of CTEPH development, following further optimization.

Purpose: Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the common terminology criteria for adverse events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data are becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied., Methods: Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed. Patients reported HRQoL at baseline, after 1 month, and end of treatment (n = 118), whereas physicians adjudicated AEs via CTCAE. Mean HRQoL scores were compared between patient randomization arms, as well as between those patients who did/did not receive dose modifications., Results: Ninety-four percent had a CTCAE grade ≥1 for at least one treatment-associated AE, with 18% undergoing dose modification due to toxicity. Mean HRQoL scores did not significantly differ at each of the three time points. Patient and physician-adjudicated reports of nausea were significantly correlated at the start (r = 0.31, p < 0.01) and end of treatment (r = 0.42, p < 0.05). There were no significant correlations between need for dose modification and HRQoL scores., Conclusions: Despite the high rate of physician-adjudicated AEs and need for dose modifications with selumetinib, patient-reported HRQoL was not impacted by treatment. Since HRQoL did not differ in the subgroup of patients who received dosage reductions due to AEs, patients may be willing to tolerate select AEs without dose modification (if medically appropriate). More research is needed to determine how to best integrate HRQoL data into clinical trial conduct., Competing Interests: The Authors declare that there is no conflict of interest.

Objective: To determine the efficacy and morbidity of repairing spontaneous cerebrospinal fluid (CSF) leaks with the middle cranial fossa (MCF) approach without the use of a lumbar drain (LD), as perioperative use of LD remains controversial., Study Design: Retrospective review from 2003 to 2015., Setting: University of Iowa Hospitals and Clinics and Indiana University Health Center., Patients: Those with a confirmed lateral skull base spontaneous CSF leaks and/or encephaloceles., Intervention: MCF approach for repair of spontaneous CSF leak and/or encephalocele without the use of lumbar drain. Assessment of patient age, sex, body mass index (BMI), and medical comorbidities., Main Outcome Measure: Spontaneous CSF leak patient characteristics (age, sex, BMI, obstructive sleep apnea) were collected. Length of stay (LOS), hospital costs, postoperative complications, CSF leak rate, and need for LD were calculated., Results: Sixty-five operative MCF repairs were performed for spontaneous CSF leaks on 60 patients (five had bilateral CSF leaks). CSF diversion with LD was used in 15 of 60 patients, mostly before 2010. After 2010, only three of 44 patients (6.7%) had postoperative otorrhea requiring LD. The use of LD resulted in significantly longer LOS (3.6 ± 1.6 versus 8.7 ± 2.9 d) and hospital costs ($29,621). There were no postoperative complications in 77% (50 of 65) of cases. Three cases required return to the operating room for complications including frontal subdural hematoma (1), subdural CSF collection (1), and tension pneumocephalus (1). No patients experienced long-term neurologic sequelae or long-term CSF leak recurrence with an average length of follow-up of 19.5 months (range 3-137 mo). The average patient BMI was 37.5 ± 8.6 kg/m. The average age was 57.5 ± 11.4 years and 68% were female. Obstructive sleep apnea was present in 43.3% (26 of 60) of patients., Conclusion: The morbidity of the MCF craniotomy for repair of spontaneous CSF leaks is low and the long-term efficacy of repair is high. Universal use of perioperative lumbar drain is not indicated and significantly increases length of stay and hospital costs. Obesity and obstructive sleep apnea are highly associated with spontaneous CSF leaks.

CHOP-based (cyclophosphamide, doxorubicin, vinca alkaloid, prednisolone) chemotherapy protocols are often recommended for treatment of feline lymphoma. While maintenance-free CHOP-based protocols have been published and readily used in dogs, there is limited literature regarding similar maintenance-free protocols in cats. The purpose of this study was to describe the outcome of cats with intermediate- to high-grade lymphoma that were prescribed a modified 25-week University of Wisconsin-Madison (UW-25) chemotherapy protocol. A secondary objective was examination of potential prognostic factors. One hundred and nineteen cats from five institutions treated with a UW-25-based protocol were included. The Kaplan-Meier median progression-free interval (PFI) and survival time (MST) were 56 and 97 (range 2-2019) days, respectively. Cats assessed as having a complete response (CR) to therapy had significantly longer PFI and MST than those with partial or no response (PFI 205 versus 54 versus 21 days, respectively, P < 0.0001 and MST 318 versus 85 versus 27 days, respectively, P < 0.0001)., Competing Interests: None of the authors of this paper have financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of this paper., (© 2015 John Wiley & Sons Ltd.)

Background: There is a paucity of research on psychosocial treatments for depression in adults with intellectual disability (ID). In this pilot study, we explored the efficacy of a group CBT treatment that involved a caregiver component in adults with mild ID with a depressive disorder., Method: Sixteen adults with mild ID and a depressive disorder participated in a 10-week group CBT treatment and 8 adults with mild ID with a depressive disorder served as a treatment as usual (TAU) control group. Adults with mild ID and caregivers completed measures of depressive symptoms, behavior problems, and social skills at pre-treatment, post-treatment, and a 3-month follow-up. Adults with mild ID also completed a series of tasks to measure their understanding of the principles of cognitive therapy pre- and post-treatment., Results: The CBT group demonstrated significant decreases in depressive symptoms and behavior problems from pre-treatment to post-treatment and these effects were maintained at a 3-month follow-up. The CBT group demonstrated significant improvements in their ability to infer emotions and thoughts based on various situation-thought-emotion pairings from pre-treatment to post-treatment., Conclusions: Findings indicate that adults with mild ID with a depressive disorder benefitted from a group CBT treatment with a caregiver component. Moreover, adults with mild ID appeared to benefit, at least in part, from the cognitive therapy components of the treatment, in addition to the behavior therapy components.

FK228 [systematic name: (1S,4S,7Z,10S,16E,21R)-7-ethyl-idene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetra-za--bicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone], C(24)H(36)N(4)O(6)S(2), also known as FR901228, depsipeptide, NSC 630176, romidepsin, and marketed as Istodax by Celgene Corporation, is crystallized from ethyl acetate in P2(1) as compared to the absolute configuration of FK228, first crystallized from methanol in P2(1)2(1)2(1) [Shigematsu et al. (1994 ▶). J. Anti-biot.47, 311-314]. A slight difference is observed between the absolute configuration of FK228 and the present structure. The molecular structure is stabilized by intramolecular N-H⋯O hydrogen bonds. In the crystal, molecules are linked via N-H⋯O hydrogen bonds.

THAILANDEPSIN A [SYSTEMATIC NAME: (E)-(1S,5S,6R,9S,20R)-6-[(2S)-butan-2-yl]-5-hy-droxy-20-[2-(meth-yl-sulfan-yl)eth-yl]-2-oxa-11,12-dithia-7,19,22-triaza-bicyclo-[7.7.6]docosa-15-ene-3,8,18,21-tetra-one], C(23)H(37)N(3)O(6)S(3), is a newly reported [Wang et al. (2011). J. Nat. Prod. doi:10.1021/np200324x] bicyclic depsipeptide that has potent histone deacetyl-ase inhibitory activity and broad-spectrum anti-proliferative activity. The absolute configuration of thailandepsin A has been determined from the anomalous dispersion and the stereochemistry of all chiral C atoms. Intra-molecular N-H⋯O and N-H⋯S hydrogen bonds occur. Inter-molecular N-H⋯O and O-H⋯O hydrogen bonds are observed in the crystal structure.

The purpose of this study was to understand the mechanism responsible for joint capsule shrinkage after nonablative laser application in an in-vitro sheep model. Femoropatellar joint capsular tissue specimens harvested from 20 adult sheep were treated with one of three power settings of a holmium:yttrium-aluminum-garnet laser or served as a control. Laser treatment significantly shortened the tissue and decreased tissue stiffness in all three laser groups, whereas failure strength was not altered significantly by laser treatment. Transmission electron microscopic examination showed swollen collagen fibrils and loss of membrane integrity of fibroblasts. A thermometric study revealed nonablative laser energy caused tissue temperature to rise in the range of 64 degrees C to 100 degrees C. Electrophoresis after trypsin digestion of the tissue revealed significant loss of distinct alpha bands of Type I collagen in laser treated samples, whereas alpha bands were present in laser treated tissue without trypsin digestion. The results of this study support the concept that the primary mechanism responsible for the effect of nonablative laser energy is thermal denaturation of collagen in joint capsular tissue associated with unwinding of the triple helical structure of the collagen molecule.

Although only humans use spoken language, the vocal communication of many animals shares some features with language. Within the context of their family, normal children and young non-human primates develop proficiency in the nuances of their species-specific vocal communication system. Engaging in speech-like phonetic activity, or babbling, occurs in all normal children regardless of their native language. Similar periods of vocal development have not been described previously for non-human primates. However, in the pygmy marmoset, a South American monkey, we found that the primary vocal behavior of infants parallels many characteristics of human infant babbling. These analogous features include universality, repetition, use of a subset of the adult vocal repertoire, recognizably adult-like vocal structure and lack of a clear vocal referent. Also, like human infants, young marmosets develop in a closely knit family unit that includes both parents and often older siblings. In this context, the babbling-like behavior of the marmoset infant stimulates interaction with caregivers, thereby serving a key role in the infant's own development. These developmental and social processes indicate that the study of vocal development in non-human primate species can provide insights into the function of babbling in humans.

The equilibrium theory of island biogeography provided a framework for describing the colonization of apple leaf 'islands' by filamentous fungi. Surface sterilization of living leaves in situ by hydrogen peroxide allowed the colonization process to be followed from its inception. Numbers of species of filamentous fungi per leaf fluctuated from 6 to 21 during the first 2 weeks of colonization and equilibrated at about 12 by the third week. Turnover occurred in species composition at equilibrium. The equilibrium number of species was not related to leaf area.The presence of an equilibrium condition with turnover on the leaf surfaces is consistent with two key tenets of the theory of island biogeography. However, the apparent back of a species-area relationship is inconsistent with the island model.