Elevated Southern Hemisphere moisture availability during glacial periods.

Late Pleistocene ice-age climates are routinely characterized as having imposed moisture stress on low- to mid-latitude ecosystems1-5. This idea is largely based on fossil pollen evidence for widespread, low-biomass glacial vegetation, interpreted as indicating climatic dryness6. However, woody plant growth is inhibited under low atmospheric CO2 (refs. 7,8), so understanding glacial environments requires the development of new palaeoclimate indicators that are independent of vegetation9. Here we show that, contrary to expectations, during the past 350 kyr, peaks in southern Australian climatic moisture availability were largely confined to glacial periods, including the Last Glacial Maximum, whereas warm interglacials were relatively dry. By measuring the timing of speleothem growth in the Southern Hemisphere subtropics, which today has a predominantly negative annual moisture balance, we developed a record of climatic moisture availability that is independent of vegetation and extends through multiple glacial-interglacial cycles. Our results demonstrate that a cool-moist response is consistent across the austral subtropics and, in part, may result from reduced evaporation under cool glacial temperatures. Insofar as cold glacial environments in the Southern Hemisphere subtropics have been portrayed as uniformly arid3,10,11, our findings suggest that their characterization as evolutionary or physiological obstacles to movement and expansion of animal, plant and, potentially, human populations10 should be reconsidered.

Clocks, cancer, and chronochemotherapy.

The circadian clock coordinates daily rhythmicity of biochemical, physiologic, and behavioral functions in humans. Gene expression, cell division, and DNA repair are modulated by the clock, which gives rise to the hypothesis that clock dysfunction may predispose individuals to cancer. Although the results of many epidemiologic and animal studies are consistent with there being a role for the clock in the genesis and progression of tumors, available data are insufficient to conclude that clock disruption is generally carcinogenic. Similarly, studies have suggested a circadian time-dependent efficacy of chemotherapy, but clinical trials of chronochemotherapy have not demonstrated improved outcomes compared with conventional regimens. Future hypothesis-driven and discovery-oriented research should focus on specific interactions between clock components and carcinogenic mechanisms to realize the full clinical potential of the relationship between clocks and cancer.

Reasons to believe in vaporization: a review of the benefits of photo-selective and transurethral vaporization.

PURPOSE: In the current review, we will discuss the state of the literature of vaporization of the prostate for the treatment of benign prostatic enlargement (BPE). We discuss two methods of vaporization of the prostate: Transurethral Vaporization of the Prostate (TUVP) and Greenlight Photo-selective Vaporization of the Prostate (PVP). METHODS: A comprehensive review of the literature was performed on TUVP and PVP. The literature on transurethral resection of the prostate (TURP) was also extensively reviewed as a comparative surgical method. RESULTS: The evidence shows that TUVP appears to be the safer choice, as compared to TURP due to less intra- and peri-operative complications. PVP was associated with less bleeding complications than TURP with outpatient discharge. Importantly, PVP was not associated with serious bleeding events requiring blood transfusions or medical treatment in patients under anticoagulation or antiplatelet therapies. PVP was also shown to be a cost-effective option compared to TURP. CONCLUSION: Prostate vaporization for the treatment of BPE appears to be an efficient and safer alternative to TURP. Vaporization techniques, particularly Greenlight PVP, should be offered to most men, especially those under anticoagulation therapy, as well as patients at risk of bleeding complications.

The use of random forests modelling to detect yeast-mannan sensitive bacterial changes in the broiler cecum.

In this study, sequencing of the 16S rRNA gene targeting the V4-V6 regions was conducted to assess the cecal microbial alterations in response to dietary supplementation with a yeast derived mannan rich fraction (MRF) in standard commercial broiler production settings across four separate broiler trials. The resulting data was analysed to identify consistent changes in the bacterial community structure of the broiler cecum in response to MRF supplementation. Subsequently, the datasets from each individual trial were pooled and analysed for differences between control and MRF supplemented diets at day 35 posthatch. The results from this analysis showed that Phylum Firmicutes was decreased and Phylum Bacteroidetes was increased across all four trials at day 35 posthatch when compared to the control. An extension of the random forest bioinformatics approach to discover a highly relevant set of microbial operational taxonomic units (OTUs) which are indicative of MRF supplementation in the broiler cecum was then used. This approach has enabled the identification of a novel set of yeast-mannan sensitive bacterial OTUs in the cecal microbiome. This information will be helpful in developing potential future nutritional strategies and will be favourable to the poultry industry.

Major Reduction in Axillary Lymph Node Dissections After Neoadjuvant Systemic Therapy for Node-Positive Breast Cancer by combining PET/CT and the MARI Procedure.

BACKGROUND: Axillary lymph node dissection (ALND) is frequently performed for node-positive (cN+) breast cancer patients. Combining positron emission tomography/computed tomography (PET/CT) before-NST and the MARI (marking axillary lymph nodes with radioactive iodine seeds) procedure after neoadjuvant systemic therapy (NST) has the potential for avoiding unnecessary ALNDs. This report presents the results from implementation of this strategy. METHODS: All breast cancer patients treated with NST at the Netherlands Cancer Institute who underwent a PET/CT and the MARI procedure from July 2014 to July 2017 were included in the study. All the patients underwent tailored axillary treatment according to a protocol based on the combined results of PET/CT before NST and the MARI procedure after NST. With this protocol, patients showing one to three FDG-avid axillary lymph nodes (ALNs) on PET/CT (cN<4) and a tumor-negative MARI node receive no further axillary treatment. All cN (<4) patients with a tumor-positive MARI node receive locoregional radiotherapy, as well as patients with four or more FDG-avid ALNs [cN(4+)] and a tumor-negative MARI node after NST. An ALND is performed only for cN(4+) patients with a tumor-positive MARI node. RESULTS: The data of 159 patients who received a PET/CT before NST and a MARI procedure after NST were analyzed. Of these patients, 110 had one to three FDG-avid ALNs and 49 patients showed four or more FDG-avid ALNs on PET/CT before NST. For 130 patients (82%), ALND was omitted. Locoregional radiotherapy was administered to 91 patients (57%), and 39 patients (25%) received no further axillary treatment. CONCLUSION: Combining pre-NST axillary staging with PET/CT and post-NST staging with the MARI procedure resulted in an 82% reduction of ALNDs for cN + breast cancer patients.

The influence of Antarctic subglacial volcanism on the global iron cycle during the Last Glacial Maximum.

Marine sediment records suggest that episodes of major atmospheric CO2 drawdown during the last glacial period were linked to iron (Fe) fertilization of subantarctic surface waters. The principal source of this Fe is thought to be dust transported from southern mid-latitude deserts. However, uncertainty exists over contributions to CO2 sequestration from complementary Fe sources, such as the Antarctic ice sheet, due to the difficulty of locating and interrogating suitable archives that have the potential to preserve such information. Here we present petrographic, geochemical and microbial DNA evidence preserved in precisely dated subglacial calcites from close to the East Antarctic Ice-Sheet margin, which together suggest that volcanically-induced drainage of Fe-rich waters during the Last Glacial Maximum could have reached the Southern Ocean. Our results support a significant contribution of Antarctic volcanism to subglacial transport and delivery of nutrients with implications on ocean productivity at peak glacial conditions.

A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia.

Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35-44 years, either RIC or myeloablative conditioning was permitted. The aim was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50-0.85), P=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37%; adjusted HR 1.50 (1.01-2.21), P=0.04) due to lower NRM (34 vs 14%, P=0.002) In adjusted analyses, there was a survival benefit for sibling RIC over chemotherapy (59 vs 49%, HR 0.75 (0.57-0.97), P=0.03), with consistent results in intermediate and adverse-risk patients. In patients aged 35-44 years, best outcomes were seen with a sibling RIC transplant, although a comparison with chemotherapy and myeloablative transplant was not significant in adjusted analyses (P=0.3).

Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation.

This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.

Surveillance MR imaging is superior to serum tumor markers for detecting early tumor recurrence in patients with appendiceal cancer treated with surgical cytoreduction and HIPEC.

BACKGROUND: The purpose of this study was to determine if MRI surveillance is better than serum tumor makers in detecting early recurrence in patients with mucinous appendiceal neoplasm. MATERIALS AND METHODS: A total of 50 patients with appendiceal neoplasm (DPAM 11, PMCA 39) underwent abdominal and pelvic MRI prior to surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients then entered follow-up surveillance with serial MRI every 6 months and serial laboratory studies including CA 125, CEA, and CA19-9. Written reports for surveillance MRI exams were reviewed for tumor recurrence and compared with results of serial laboratory tests. Proof of tumor recurrence was by a consensus of surgery and histopathology, as well as clinical and imaging findings on serial examinations. RESULTS: During surveillance tumor recurrence was documented in 30 patients (60 %) with median time to recurrence of 13 months (range 3-56 months). MRI detected recurrent tumor in 28 patients, including 11 patients with normal laboratory values (sensitivity 0.93, specificity 0.95, accuracy 0.94, PPV 0.97, and NPV 0.90). Serial laboratory values showed tumor recurrence in 14 patients (sensitivity 0.48, specificity 1.00, accuracy 0.69, PPV 1.0, and NPV 0.57). Median survival was 50 months for 11 patients with earlier MRI detection of recurrence vs 33 months for the other 19 patients with recurrence. CONCLUSIONS: Following cytoreductive surgery and HIPEC MRI detects tumor recurrence earlier and with greater accuracy than serial tumor markers alone.

Primary hypoparathyroidism in dogs: a retrospective study of 17 cases.

OBJECTIVE: To evaluate the clinico-pathological findings, response to treatment and prevalence of complications in dogs with primary hypoparathyroidism. DESIGN: Retrospective study of 17 dogs presenting to the University of Melbourne Veterinary Clinical Centre and Murdoch University Veterinary Hospital over a 15 year period (1990 to 2004). Case records were evaluated for signalment, body weight, diet type, historical and clinical findings, serum total calcium, phosphate, albumin and parathyroid hormone concentrations, urinary fractional excretion ratios of calcium and phosphate, electrocardiogram (ECG) results, treatments administered, outcome and period of follow-up. RESULTS: The most common breeds identified were St Bernard (three dogs), Chihuahua (two dogs), German Shepherd (two dogs) and Jack Russell Terrier (two dogs). Three dogs were cross bred. Seizures, muscle tremors and fasciculations, stiff gait, tetany, muscle cramping, behavioural change and hyperventilation were the most common clinical signs. Vomiting, inappetence, diarrhoea, abdominal pain, hyperthermia, facial pruritus, ataxia, weakness, cataracts, and circling also occurred with less frequency. The mean duration of observed clinical signs preceding diagnosis was 33 days (median 13 days, range 1 to 173 days). All dogs had marked hypocalcaemia with normal or mildly increased serum albumin concentrations. Mean phosphate concentrations were significantly higher in inappetent dogs (P = 0.049). Mean serum calcium concentrations were significantly lower in dogs with cataracts compared to those without (P = 0.046). There were no other significant relationships between serum calcium or phosphate concentrations and the clinical presentation or outcome. No significant correlations were identified between the presence of a particular clinical sign and the duration of clinical signs. ECGs were obtained in four dogs and all exhibited QT interval prolongation due to a ST-segment prolongation. Sixteen of 17 dogs were treated successfully for hypocalcaemia and discharged from hospital. Acute management included parenteral calcium gluconate (10 dogs) and intravenous anticonvulsants (five dogs). Chronic therapy included oral vitamin D analogues and calcium supplementation. Treatment complications occurred in two dogs and included acute renal failure (one dog) and iatrogenic tissue necrosis following subcutaneous calcium administration (one dog). The mean follow-up period was 14.5 months (median 13 months, range 0 to 39 months). Twelve dogs were alive at the last follow up and two dogs were euthanased for unrelated reasons. The type of vitamin D analogue used was not associated with outcome. CONCLUSION: Primary hypoparathyroidism was an uncommon diagnosis in dogs. Saint Bernards, cross bred dogs, German Shepherd dogs and Terrier breeds were most commonly affected. Neurological signs were the most common presenting clinical signs, although alimentary signs may have been more common than previously reported. Dogs with primary hypoparathyroidism appeared to have a good prognosis following initiation of calcium supplementation and vitamin D therapy. Complications of treatment were uncommon and could be minimised with regular monitoring.

Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis.

BACKGROUND: Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for approximately 15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. METHODS AND FINDINGS: An animal model of LCA, the Lrat-/- mouse, recapitulates clinical features of the human disease. Here, we report that two interventions--intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds--each restore retinal function to Lrat-/- mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to approximately 50% of wild-type levels (p < 0.05 versus wild-type and knockout controls), and pupillary light responses (PLRs) of Lrat-/- mice increased approximately 2.5 log units (p < 0.05). Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration) also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from approximately 5% of wild-type levels in Lrat-/- mice to approximately 50% of wild-type levels in treated Lrat-/- mice (p < 0.05 versus wild-type and knockout controls). The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and approximately 1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. CONCLUSION: Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness.

Effect of vitamin A depletion on nonvisual phototransduction pathways in cryptochromeless mice.

Mice exhibit multiple nonvisual responses to light, including 1) photoentrainment of circadian rhythm; 2) "masking," which refers to the acute effect of light on behavior, either negative (activity suppressing) or positive (activity inducing); and 3) pupillary constriction. In mammals, the eye is the sole photosensory organ for these responses, and it contains only 2 known classes of pigments: opsins and cryptochromes. No individual opsin or cryptochrome gene is essential for circadian photoreception, gene photoinduction, or masking. Previously, the authors found that mice lacking retinol-binding protein, in which dietary depletion of ocular retinaldehyde can be achieved, had normal light signaling to the SCN, as determined by per gene photoinduction. In the present study, the authors analyzed phototransduction to the SCN in vitamin A-replete and vitamin A-depleted rbp-/- and rbp-/-cry1-/-cry2-/- mice using molecular and behavioral end points. They found that vitamin A-depleted rbp-/- mice exhibit either normal photoentrainment or become diurnal. In contrast, while vitamin A-replete rbp-/-cry1-/-cry2-/- mice are light responsive (with reduced sensitivity), vitamin A-depleted rbp-/-cry1-/-cry2-/- mice, which presumably lack functional opsins and cryptochromes, lose most behavioral and molecular responses to light. These data demonstrate that both cryptochromes and opsins regulate nonvisual photoresponses.

Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver.

Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat-/-) mouse. Despite the expression of LRAT in multiple tissues, the Lrat-/- mouse develops normally. The histological analysis and electron microscopy of the retina for 6-8-week-old Lrat-/- mice revealed that the rod outer segments are approximately 35% shorter than those of Lrat+/+ mice, whereas other neuronal layers appear normal. Lrat-/- mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat-/- mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation.

Crohn disease with endoscopic correlation: single-shot fast spin-echo and gadolinium-enhanced fat-suppressed spoiled gradient-echo MR imaging.

PURPOSE: To compare T2-weighted breath-hold single-shot fast spin-echo (SE) and gadolinium-enhanced spoiled gradient-echo (GRE) MR imaging with contrast material administered orally and rectally for evaluating patients with Crohn disease. MATERIALS AND METHODS: Twenty-eight patients with Crohn disease received 2% barium sulfate and water enema. The abdomen and pelvis were imaged with transverse and coronal single-shot fast SE and gadolinium-enhanced spoiled GRE MR imaging. Two radiologists reviewed the two types of images for bowel disease. The extent, severity, and conspicuity of the disease were determined. Proof of bowel disease at MR imaging was compared with that at endoscopy, barium study, and surgery. Statistical analysis was performed with the McNemar test. RESULTS: Twenty-five of 28 patients had proven abnormal bowel segments. The per-patient sensitivity of gadolinium-enhanced spoiled GRE MR imaging for the two radiologists was 100% and 96% versus 60% and 60% (P <.05) with single-shot fast SE MR imaging. Gadolinium-enhanced spoiled GRE MR images depicted more segments (54 and 52 of 61 segments; sensitivity, 89% and 85%, respectively) of the diseased bowel than did single-shot fast SE MR images (31 and 32 of 61 segments; sensitivity, 51% and 52%, respectively; P <.001). Severity of Crohn disease was correctly depicted at gadolinium-enhanced spoiled GRE imaging in 93% of patients versus in 43% of patients at single-shot fast SE imaging. CONCLUSION: In patients with Crohn disease, gadolinium-enhanced fat-suppressed spoiled GRE MR imaging better depicted the extent and severity of intestinal disease compared with single-shot fast SE imaging.

Assessment of outcomes at alternative medicine cancer clinics: a feasibility study.

OBJECTIVE: This pilot study tested the feasibility of performing outcomes and more advanced research regarding cancer patients at two complementary and alternative (CAM) clinics. The primary objectives were to determine the feasibility of (1) obtaining and collecting data from medical records, (2) determining 5-year survival, and (3) comparing 5-year survival to that of conventional treatment. In addition, in this paper we present the barriers and recommend strategies to facilitate high-quality research. SETTINGS/LOCATION: The Bio-Medical Center in Tijuana, Mexico, and the Livingston Foundation Medical Center in San Diego, California. SUBJECTS: New patients who were treated for cancer during 1992 at the Livingston Foundation Medical Center and during the first quarter of 1992 at the Bio-Medical Center. RESULTS: Charts were available for 89.6% of the 307 new patients treated at the Bio-Medical Center; 149 (54%) patients were treated for cancer and 65 (43.6%) cases were confirmed by pathology reports. In contrast, all records were available for 193 new patients treated for cancer at the Livingston Clinic; 152 (78.8%) cases had pathology confirmation. At both clinics, patients were equally divided by gender and were predominantly Caucasian, were married, and were U.S. residents. On average, patients were 51-54 years old and within 1 year of diagnosis for breast, colorectal, lung, or male genital cancer. Most patients (61.1%-63.7%) arrived with distant or regional disease after conventional surgery and/or chemotherapy/radiotherapy. Survival at 5 years was determined for 57.0% at the Bio-Medical Center (11.4% were alive and 45.6% were deceased) and 94.8% at Livingston (14.5% were alive and 80.3% were deceased). The limited number of cases by cancer site prevented comparison to conventional treatment. CONCLUSIONS: Historical, widespread use of clinics such as these with anecdotal reports of extraordinary survival merit prospective, systematic monitoring of patient outcomes. For data to be meaningful, however, disease status must be pathologically confirmed and patient follow-up improved.

Coley toxins immunotherapy: a retrospective review.

OBJECTIVE: Coley toxins are administered to cancer patients worldwide, though clinical studies assessing efficacy either alone or in combination with conventional cancer therapy are limited. This article provides an overview of Coley toxins immunotherapy and compares the survival experience of cancer patients who received Coley toxins for renal, ovarian, breast cancer, or soft-tissue sarcomas with patients who received conventional treatment other than radiation. DATA SOURCES: Cases were compiled from 5 of 18 monographs by Helen Coley Nauts. STUDY SELECTION: Using a retrospective cohort design with external controls, 128 Coley cases treated in New York from 1890 to 1960 were compared with 1675 controls from the Surveillance Epidemiology End Result (SEER) population-based cancer registry who received a cancer diagnosis in 1983. DATA EXTRACTION: Groups were matched on age, sex, ethnicity, site, stage, and treatment status (i.e., no radiotherapy). DATA SYNTHESIS: The Cox proportional hazards model controlled for stage and menopausal status (when applicable) and the hazard ratio and 95% CI defined the odds of site-specific survival from date of diagnosis to last follow-up. Compared to the SEER population, risk of death within 10 years was not significantly different in Coley patients treated for renal, ovarian, breast cancer, or soft-tissue sarcomas. CONCLUSIONS: This study suggests that patients treated with surgery and Coley toxins between 1890 and 1960 experienced survival rates comparable to those of patients diagnosed in 1983 and treated with nonradiotherapeutic conventional approaches. The study is limited by small sample sizes, possibly inaccurate technology for staging during Coley time, and potential selection bias with Coley patients.

New Metallacarborane Chemistry: Molybdenum and Tungsten Carbonyl Multidecker Sandwiches. Cluster Dimers Linked via Metal-Metal Bonds(1).

This article reports the synthesis, characterization, and chemistry of the first molybdenum and tungsten complexes bearing small carborane ligands, including novel M-M-linked dicluster species. The reaction of the nido-2,3-Et(2)C(2)B(4)H(4)(2)(-) dianion with (RCN)(3)M(CO)(3) reagents (M = Mo, W; R = Me, Et) gave the (Et(2)C(2)B(4)H(4))M(CO)(3)(2)(-) anions, which were isolated as lithium (12-crown-4) salts 1b (M = Mo) and 2b (M = W). Treatment of 1b and 2b with Ph(4)PX (X = Cl, Br, I) followed by triflic acid afforded the dimeric products [(Et(2)C(2)B(4)H(4))Mo(CO)(2)](2)(&mgr;-X)(2) (X = Cl (3a), Br (3b), I (3c)) and the corresponding tungsten dimers 4a-c, all of which are red or orange air-stable crystalline solids. X-ray crystallography on 3b revealed a geometry without precedent in small metallacarborane dimers, in which two MC(2)B(4) pentagonal pyramidal clusters are linked via an intercluster metal-metal bond. From NMR and other spectroscopic evidence, the remaining dimeric products 3a, 3c, and 4a-c are proposed to have structures similar to 3b. Decapitation of 3b with HCl/EtOAc in THF gave red solid [(Et(2)C(2)B(3)H(5))Mo(CO)(2)](2)(&mgr;-Br)(2) (5), which is proposed to have two open planar C(2)B(3) end rings and, hence, is a potential building block for linear polymers via deprotonation and metal-ion-stacking reactions. Compound 3b was also generated in a different reaction, involving the nido-Et(2)C(2)B(4)H(5)(-) anion and [Mo(CO)(4)Br](2)[&mgr;-Br](2) which also produced the bis(carboranyl)molybdenum complex (Et(2)C(2)B(4)H(4))(2)Mo(CO)(2) (6), a nearly colorless solid for which a bent sandwich structure is postulated. The reaction of the nido-cobaltacarborane anion CpCo(Et(2)C(2)B(3)H(4))(-) with [Mo(CO)(4)Cl](2)[&mgr;-Cl](2) in toluene gave two isolable products, red CpCo(Et(2)C(2)B(3)H(3))Mo(CO)(4) (7) and dark red [CpCo(Et(2)C(2)B(3)H(3))](2)Mo(CO)(2) (8), which have, respectively, triple-decker and bent-tetradecker sandwich structures based on X-ray crystallographic structure determinations. The reaction of CpCo(Et(2)C(2)B(3)H(4))(-) with [Mo(CO)(4)Br](2)[&mgr;-Br](2) in toluene gave 8 and a known fused-cluster complex Cp(2)Co(2)(Et(4)C(4)B(6)H(6)) (9). Treatment of the CpCo(Et(2)C(2)B(3)H(4))(-) anion with [W(CO)(4)Br](2)[&mgr;-Br](2) afforded red crystalline CpCo(Et(2)C(2)B(3)H(3))W(CO)(4) (10), which on reaction with PhLi followed by Me(3)OBF(4) gave 11, a B(5)-benzyl derivative of 10. X-ray diffraction analyses established triple-decker sandwich structures for both compounds. The new products were characterized by multinuclear NMR, IR, UV-vis, and mass spectroscopy, and elemental analysis, supplemented by electrochemical data on 3b, 8, and 11.

Improving office-based physician's prevention practices for sexually transmitted diseases.

OBJECTIVE: To determine whether office-based interventions increase primary care physicians' risk assessment of and counseling practices for patients regarding sexually transmitted diseases and the human immunodeficiency virus (HIV). DESIGN: Randomized controlled clinical trial. SETTING: Washington, D.C., Metropolitan Statistical Area. STUDY PARTICIPANTS: Office-based primary care physicians (family or general practice, internal medicine, and obstetrics-gynecology). INTERVENTION: Mailed educational materials alone or coupled with a simulated patient instructor office visit. MEASUREMENTS: Self-reported and observed frequency of assessing and counseling patients regarding their risk factors for sexually transmitted diseases and HIV infection. Participants were interviewed by telephone before and after the intervention (n = 757). A subset of participants (n = 194) was also observed after the intervention by simulated patient evaluators in blinded office visits. RESULTS: 89% of physicians who received both educational materials and a simulated patient instructor visit reported that they reviewed the educational materials compared with 53% of those who only received the educational materials (P < or = 0.001). Physicians in the combined intervention group had higher self-reported and observed rates for several risk assessment questions and counseling recommendations than did physicians in the control group or the group that only received educational materials. Seventy-three percent of physicians of the combined intervention group reported an increase in counseling patients about reducing risky sexual behavior compared with 53% of the group receiving only educational materials and 42% of the control group (P < or = 0.001). CONCLUSIONS: Mailed educational materials combined with an office visit by a simulated patient instructor for role-play and feedback on clinical performance increased the frequency of office-based physicians' risk assessment and risk reduction counseling of patients for sexually transmitted diseases and HIV infection.