Surgical repair of large segmental bone loss with the induced membrane technique: patient reported outcomes are comparable to nonunions without bone loss.

OBJECTIVE: To compare the outcomes of patients with segmental bone loss who underwent repair with the induced membrane technique (IMT) with a matched cohort of nonunion fractures without bone loss. DESIGN: Retrospective analysis on prospectively collected data. SETTING: Academic medical center. PATIENTS: Two cohorts of patients, those with upper and lower extremity diaphyseal large segmental bone loss and those with ununited fractures, were enrolled prospectively between 2013 and 2020. Sixteen patients who underwent repair of 17 extremities with segmental diaphyseal or meta-diaphyseal bone defects treated with the induced membrane technique were identified, and matched with 17 patients who were treated for 17 fracture nonunions treated without an induced membrane. Sixteen of the bone defects treated with the induced membrane technique were due to acute bone loss, and the other was a chronic aseptic nonunion. MAIN OUTCOME MEASUREMENTS: Healing rate, time to union, functional outcome scores using the Short Musculoskeletal Functional Assessment (SMFA) and pain assessed by the Visual Analog Scale (VAS). RESULTS: The initial average defect size for patients treated with the induced membrane technique was 8.85 cm. Mean follow-up times were similar with 17.06 ± 10.13 months for patients treated with the IMT, and 20.35 ± 16.68. months for patients treated without the technique. Complete union was achieved in 15/17 (88.2%) of segmental bone loss cases treated with the IMT and 17/17 (100%) of cases repaired without the technique at the latest follow up visit. The average time to union for patients treated with the induced membrane technique was 13.0 ± 8.4 months and 9.64 ± 4.7 months for the matched cohort. There were no significant differences in reported outcomes measured by the SMFA or VAS. Patients treated with the induced membrane technique required more revision surgeries than those not treated with an induced membrane. CONCLUSION: Outcomes following treatment of acute bone loss from the diaphysis of long bones with the induced membrane technique produces clinical and radiographic outcomes similar to those of long bone fracture nonunions without bone loss that go on to heal. LEVEL OF EVIDENCE: III.

Ten-step minimally invasive slalom unilateral laminotomy for bilateral decompression (sULBD) with navigation.

BACKGROUND: Unilateral laminotomy for bilateral decompression (ULBD) is a MIS surgical technique that offers safe and effective decompression of lumbar spinal stenosis (LSS) with a long-term resolution of symptoms. Advantages over conventional open laminectomy include reduced expected blood loss, muscle damage, mechanical instability, and less postoperative pain. The slalom technique combined with navigation is used in multi-segmental LSS to improve the workflow and effectiveness of the procedure. METHODS: We outline ten technical steps to achieve a slalom unilateral laminotomy for bilateral decompression (sULBD) with navigation. In a retrospective case series, we included patients with multi-segmental LSS operated in our institution using the sULBD between 2020 and 2022. The primary outcome was a reduction in pain measured by Visual Analogue Scale (VAS) for back pain and leg pain and Oswestry Disability Index (ODI). RESULTS: In our case series (N = 7), all patients reported resolution of initial symptoms on an average follow-up of 20.71 ± 9 months. The average operative time and length of hospital stay were 196.14 min and 1.67 days, respectively. On average, VAS (back pain) was 4.71 pre-operatively and 1.50 on long-term follow-up of an average of 19.05 months. VAS (leg pain) decreased from 4.33 to 1.21. ODI was reported as 33% pre-operatively and 12% on long-term follow-up. CONCLUSION: The sULBD with navigation is a safe and effective MIS surgical procedure and achieves the resolution of symptoms in patients presenting with multi-segmental LSS. Herein, we demonstrate the ten key steps required to perform the sULBD technique. Compared to the standard sULBD technique, the incorporation of navigation provides anatomic localization without exposure to radiation to staff for a higher safety profile along with a fast and efficient workflow.

Microbiome of infected fracture nonunion: Does it affect outcomes?

BACKGROUND: Infected fracture nonunions often require prolonged treatment and recovery courses. It is unclear whether the bacterial microbiome influences the time to healing as well as the eradication of infection. The goals of this study are (1) to assess the bacterial microbiome affecting infected nonunions and (2) to evaluate the effects of bacterial speciation on associated outcomes. METHODS: Between 2006 and 2022, data from 551 adult patients from a single academic institution who presented with a fracture nonunion were analyzed retrospectively for infection. All patients underwent revision surgery with three sets of cultures obtained intra-operatively. Patients with significant intra-operative cultures were grouped into gram-positive and gram-negative culture cohorts. These patients were managed with a standardized protocol involving surgical debridement, nonunion site fixation, and culture-directed antibiotic treatment. Primary outcome was time to fracture union. Secondary outcomes included number of re-operations and eventual amputation or reconstructive surgery. RESULTS: 56 nonunion patients (10 %) were diagnosed with an infected nonunion (44 g-positive, 12 g-negative). Of these, 3 g-positive patients received an amputation or arthroplasty procedure prior to fracture union, and seven were lost to follow-up. There were no significant differences in age, gender, or nonunion site between cohorts. Most nonunions occurred in the lower extremity. The most common bacteria were staph species (54.3 %). 36 g-positive and 10 g-negative patients achieved fracture union. Time to union was on average 158.4 days longer in the gram-negative cohort-but did not reach statistical significance (446.8 days gram-positive, 662.3 days gram-negative, p = 0.69). There was no difference in re-operation rates (1.9 % gram-positive, 2.2 % gram-negative, p = 0.84). CONCLUSIONS: Patients with infected nonunions had wide-ranging bacterial contamination that were treated successfully using a standardized protocol. However, patients with any gram-negative culture trended toward a delay in time to union.

No decay in outcomes at a mean 8 years following surgical treatment for aseptic fracture nonunion.

PURPOSE: The purpose of this study is to compare medium to long term patient reported outcomes to one-year data for patients treated surgically for an aseptic fracture nonunion. METHODS: 305 patients surgically treated for a fracture-nonunion were prospectively followed. Data collected included pain scores measured by the Visual Analog Scale (VAS), clinical outcomes assessed by the Short Musculoskeletal Functional Assessment (SMFA), and range of motion. 75% of patients in this study had lower extremity fracture nonunions and 25% had upper extremity fracture nonunions. Femur fracture nonunions were the most common. Data at latest follow-up was compared to one-year follow-up using the independent t-test. RESULTS: Sixty-two patients were available for follow-up data at an average of eight years. There were no differences in patient reported outcomes between one and eight years according to the standardized total SMFA (p = 0.982), functional index SMFA (p = 0.186), bothersome index SMFA (p = 0.396), activity index SMFA (p = 0.788), emotional index SMFA (p = 0.923), or mobility index SMFA (p = 0.649). There was also no difference in reported pain (p = 0.534). Range of motion data was collected for patients who followed up in clinic for an average of eight years after their surgical treatment. 58% of these patients reported a slight increase in range of motion at an average of eight years. CONCLUSION: Patient functional outcomes, range of motion, and reported pain all normalize after one year following surgical treatment for fracture nonunion and do not change significantly at an average of eight years. Surgeons can feel confident in counseling patients that their results will last and they do not need to follow up beyond one year, barring pain or other complications. LEVEL OF EVIDENCE: Level IV.

Revisiting the Conformational Isomerism of Dihaloethanes: A Hybrid Computational and Experimental Laboratory for the Undergraduate Curriculum.

The conformational isomerism of disubstituted ethanes is a well-known concept that is part of every chemistry curriculum. Due to the species' simplicity, studying the (free) energy difference between the gauche and anti isomers has been the testing ground of experimental and computational techniques, such as Raman and IR spectroscopy, quantum chemistry, and atomistic simulations. While students normally receive formal training in spectroscopic techniques during their early undergraduate years, computational methods often receive less attention. In this work, we revisit the conformational isomerism of 1,2-dichloroethane and 1,2-dibromoethane and design a hybrid computational and experimental laboratory for our undergraduate chemistry curriculum with a focus on introducing computational techniques as a complementary research tool to experimentation. We show how commonly available Raman spectrometers and atomistic simulations performed on desktop computers can be combined to study the conformational isomerism of disubstituted ethanes while discussing the advantages and limitations of the different approaches.

Patient obesity is associated with severity of proximal humerus fractures, not outcomes.

PURPOSE: The purpose of this study is to evaluate the effect of obesity on the outcome of operatively treated proximal humerus fractures. METHODS: Between December 2003 and October 2020, 240 patients with proximal humerus fractures requiring surgery were prospectively followed and classified according to the international AO/Orthopedic Trauma Association (AO/OTA) and Neer classifications. Patients' body mass indexes (BMI) were calculated and used to identify two groups, BMI ≥ 30 kg/cm (obese) and < 30 kg/cm (non-obese). Independent t tests were used for statistical analysis of continuous variables and χ2 tests for categorical variables. Regression analysis was performed to determine if BMI was a predictor of fracture pattern severity as determined by the AO/OTA classification. RESULTS: Overall, 223 patients who sustained proximal humerus fractures were analyzed. Patient age at time of injury was 60.5 ± 13.7 years. There were 67 AO/OTA 11A, 79 AO/OTA 11B, and 77 AO/OTA 11C fracture types. Seventy-two patients (32.3%) were obese. No significant differences were seen between groups in regard to demographic variables, Neer classification, or functional and clinical outcomes as determined by DASH scores and shoulder ROM, respectively. Statistical analyses confirmed that obesity is associated with more severe fracture patterns of the proximal humerus as categorized by the AO/OTA classification. An independent t test confirmed that BMI was significantly higher in the complex fracture group based on the AO/OTA classification (p = 0.047). Regression analysis also demonstrated that age (p = 0.005) and CCI (p = 0.021) were predictors of more severe fractures, while BMI approached significance (p = 0.055) based on the AO/OTA classification. CONCLUSION: A significantly higher incidence of complex proximal humerus fracture patterns is observed in patients with higher body mass indexes based on the AO/OTA classification. Age and CCI are also associated with more severe fracture patterns of the proximal humerus as determined by the AO/OTA classification. No differences were seen in outcomes or complication rates between obese patients and non-obese patients. LEVEL OF EVIDENCE: Level III.

Reinterpreting the Fate of Iridium(III) Photocatalysts─Screening a Combinatorial Library to Explore Light-Driven Side-Reactions.

Photoredox catalysts are primarily selected based on ground and excited state properties, but their activity is also intrinsically tied to the nature of their reduced (or oxidized) intermediates. Catalyst reactivity often necessitates an inherent instability, thus these intermediates represent a mechanistic turning point that affords either product formation or side-reactions. In this work, we explore the scope of a previously demonstrated side-reaction that partially saturates one pyridine ring of the ancillary ligand in heteroleptic iridium(III) complexes. Using high-throughput synthesis and screening under photochemical conditions, we identified different chemical pathways, ultimately governed by ligand composition. The ancillary ligand was the key factor that determined photochemical stability. Following photoinitiated electron transfer from a sacrificial tertiary amine, the reduced intermediate of complexes containing 1,10-phenanthroline derivatives exhibited long-term stability. In contrast, complexes containing 2,2'-bipyridines were highly susceptible to hydrogen atom transfer and ancillary ligand modification. Detailed characterization of selected complexes before and after transformation showed differing effects on the ground and excited state reduction potentials dependent on the nature of the cyclometalating ligands and excited states. The implications of catalyst stability and reactivity in chemical synthesis was demonstrated in a model photoredox reaction.

Mechanisms of Interaction of Small Hydroxylated Cryosolvents with Dehydrated Model Cell Membranes: Stabilization vs Destruction.

The mechanism by which cryosolvents such as alcohols modify and penetrate cell membranes as a function of their concentration and hydration state remains poorly understood. We conducted molecular dynamics simulations of 1,2-dioleoyl-sn-glycero-3-phosphocholine bilayers in the presence of aqueous solutions of four common penetrating hydroxylated cryosolvents (methanol, ethylene glycol, propylene glycol, and glycerol) at varying concentration ranges and across three different hydration states. All cryosolvents were found to preferentially replace water at the bilayer interface, and a reduction in hydration state correlates with a higher proportion of cryosolvent at the interface for relative concentrations. Minor differences in chemical structure had a profound effect on cryosolvent-membrane interactions, as the lone methyl groups of methanol and propylene glycol enhanced their membrane localization and penetration, but with increasing concentrations acted to destabilize the membrane structure in a process heightened at higher hydration states. By contrast, ethylene glycol and glycerol promoted and retained membrane structural integrity by forming hydrogen-bonded lipid bridges via distally located hydroxyl groups. Glycerol exhibited the highest capacity to cross-link lipids at relative concentrations, as well as promoted a bilayer structure consistent with a fully hydrated bilayer in the absence of cryosolvent for all hydration states investigated.

Multi-Phase Solvation Model for Biological Membranes: Molecular Action Mechanism of Amphotericin B.

Amphotericin B (AmB) is still the most effective drug for the treatment of systemic fungal infections in humans. Despite significant theoretical and experimental efforts trying to understand its molecular mechanism of action, the answer has remained elusive. In this work, we present a computational methodology to test the current membrane related hypotheses, namely, transmembrane ion channel, adsorption, and sterol sponge. We use a thermodynamic approach in which we represent the membrane by a multiphase solvation model with atomic detail (MMPSM) and calculate the free energy of transferring the drug between phases with different dielectric properties. Furthermore, we compare AmB to a chemical analogue with increased safety, an l-histidine methyl ester of AmB. Our findings reveal that both drugs dimerize in all solvents studied here. Also, it is energetically unfavorable for the drugs to penetrate into the hydrophobic core of the membrane, unless their concentration is high. Finally, it is thermodynamically possible that the sterols migrate from the membrane into a drug droplet adsorbed at the surface of the bilayer. In light of our results, several effects could take place in the complex antibiotic process. We suggest a molecular mechanism that connects all three hypotheses through a drug concentration dependence and propose that the drug promotes the formation of membrane toroidal pores. Because MMPSM is of general interest, we made it available at http://tripplab.com/tools/mmpsm .

Mathematical Modelling of Trachoma Transmission, Control and Elimination.

The World Health Organization has targeted the elimination of blinding trachoma by the year 2020. To this end, the Global Elimination of Blinding Trachoma (GET, 2020) alliance relies on a four-pronged approach, known as the SAFE strategy (S for trichiasis surgery; A for antibiotic treatment; F for facial cleanliness and E for environmental improvement). Well-constructed and parameterized mathematical models provide useful tools that can be used in policy making and forecasting in order to help to control trachoma and understand the feasibility of this large-scale elimination effort. As we approach this goal, the need to understand the transmission dynamics of infection within areas of different endemicities, to optimize available resources and to identify which strategies are the most cost-effective becomes more pressing. In this study, we conducted a review of the modelling literature for trachoma and identified 23 articles that included a mechanistic or statistical model of the transmission, dynamics and/or control of (ocular) Chlamydia trachomatis. Insights into the dynamics of trachoma transmission have been generated through both deterministic and stochastic models. A large body of the modelling work conducted to date has shown that, to varying degrees of effectiveness, antibiotic administration can reduce or interrupt trachoma transmission. However, very little analysis has been conducted to consider the effect of nonpharmaceutical interventions (and particularly the F and E components of the SAFE strategy) in helping to reduce transmission. Furthermore, very few of the models identified in the literature review included a structure that permitted tracking of the prevalence of active disease (in the absence of active infection) and the subsequent progression to disease sequelae (the morbidity associated with trachoma and ultimately the target of GET 2020 goals). This represents a critical gap in the current trachoma modelling literature, which makes it difficult to reliably link infection and disease. In addition, it hinders the application of modelling to assist the public health community in understanding whether trachoma programmes are on track to reach the GET goals by 2020. Another gap identified in this review was that of the 23 articles examined, only one considered the cost-effectiveness of the interventions implemented. We conclude that although good progress has been made towards the development of modelling frameworks for trachoma transmission, key components of disease sequelae representation and economic evaluation of interventions are currently missing from the available literature. We recommend that rapid advances in these areas should be urgently made to ensure that mathematical models for trachoma transmission can robustly guide elimination efforts and quantify progress towards GET 2020.

Myo1g is an active player in maintaining cell stiffness in B-lymphocytes.

B-lymphocytes are migrating cells that specialize in antigen presentation, antibody secretion, and endocytosis; these processes implicate the modulation of plasma membrane elasticity. Cell stiffness is a force generated by the interaction between the actin-cytoskeleton and the plasma membrane, which requires the participation of several proteins. These proteins include class I myosins, which are now considered to play a role in controlling membrane-cytoskeleton interactions. In this study, we identified the motor protein Myosin 1g (Myo1g) as a mediator of this phenomenon. The absence of Myo1g decreased the cell stiffness, affecting cell adhesion, cell spreading, phagocytosis, and endocytosis in B-lymphocytes. The results described here reveal a novel molecular mechanism by which Myo1g mediates and regulates cell stiffness in B-lymphocytes. © 2016 Wiley Periodicals, Inc.

Palliative Care Training in Surgical Oncology and Hepatobiliary Fellowships: A National Survey of Program Directors.

BACKGROUND: Despite previous literature affirming the importance of palliative care training in surgery, there is scarce literature about the readiness of Surgical Oncology and hepatopancreaticobiliary (HPB) fellows to provide such care. We performed the first nationally representative study of surgical fellowship program directors' assessment of palliative care education. The aim was to capture attitudes about the perception of palliative care and disparity between technical/clinical education and palliative care training. METHODS: A survey originally used to assess surgical oncology and HPB surgery fellows' training in palliative care, was modified and sent to Program Directors of respective fellowships. The final survey consisted of 22 items and was completed online. RESULTS: Surveys were completed by 28 fellowship programs (70 % response rate). Only 60 % offered any formal teaching in pain management, delivering bad news or discussion about prognosis. Fifty-eight percent offered formal training in basic communication skills and 43 % training in conducting family conferences. Resources were available, with 100 % of the programs having a palliative care consultation service, 42 % having a faculty member with recognized clinical interest/expertise in palliative care, and 35 % having a faculty member board-certified in Hospice and Palliative Medicine. CONCLUSIONS: Our data shows HPB and surgical oncology fellowship programs are providing insufficient education and assessment in palliative care. This is not due to a shortage of faculty, palliative care resources, or teaching opportunities. Greater focus one valuation and development of strategies for teaching palliative care in surgical fellowships are needed.

Theoretical study of the aqueous solvation of HgCl2: Monte Carlo simulations using second-order Moller-Plesset-derived flexible polarizable interaction potentials.

A study of the solvation of HgCl(2) including ab initio aggregates of up to 24 water molecules and the results of extensive Monte Carlo simulations for the liquid phase using MP2-derived interaction potentials is presented. The interaction potentials are flexible, polarizable, and include non-additive effects. We conclude that a cluster description of the solvation mechanism is limited when compared to the condensed phase. The molecular image derived from the MC simulations is peculiar. It resembles that of a hydrophobic solute, which explains the rather easy passage of this neutral molecule through the cell membrane; however, it also shows an intermittent binding of one, two, or three water molecules to HgCl(2) in the fashion of a hydrophilic solute.

Effect of membrane structure on the action of polyenes II: nystatin activity along the phase diagram of ergosterol- and cholesterol-containing POPC membranes.

Pores formed by the polyene antibiotic nystatin were studied in solvent-free lipid membranes. The membranes were formed by the tip-dip technique using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) with different mol fractions (0-50%) of cholesterol or ergosterol. The effects of the mol fraction of sterol and of temperature variation (15-35°C) on the activity of the pores, their unitary conductances, lifetimes and time average conductances were studied. The results were used to analyze the behavior of nystatin channels along the phase diagrams previously reported for these lipid mixtures and to propose that membrane structure is the determinant factor for the known ergosterol/cholesterol selectivity.

Effect of membrane structure on the action of polyenes: I. Nystatin action in cholesterol- and ergosterol-containing membranes.

A detailed and thorough characterization of nystatin-induced permeability on lipid bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)-containing ergosterol or cholesterol is presented. The results show that the same collection of transmembrane pores appears in membranes containing either sterol. The concentration range for the appearance of these pores is sterol-dependent. Another mechanism of action, membrane disruption, is also observed in ergosterol-POPC membranes. The greater potency of nystatin present in ergosterol-containing membranes cannot be explained simply by the longer opening times of its pores, as has been suggested; it is also due to an increased number of events in these membranes. The present results and those of a companion paper lead us to propose that membrane structure is the determining factor for drug selectivity in membranes with different sterols.

Aqueous solvation of As(OH)3: a Monte Carlo study with flexible polarizable classical interaction potentials.

A theoretical study of the hydration of arsenious acid is presented. This study included ab initio calculations and Monte Carlo simulations. The model potentials used for the simulations were ab initio derived and they include polarizability, nonadditivity, and molecular relaxation. It is shown that with these refined potentials it is possible to reproduce the available experimental evidence and therefore permit the study of clusters, as well as of the hydration process in solution. From the study of stepwise hydration and the Monte Carlo simulation of the condensed phase it is concluded that As(OH)(3) presents a hydration scheme similar to an amphipathic molecule. This phenomenon is explained as due to the existence of both a positive electrostatic potential and a localized lone pair in the vicinity of As. These results are used to rationalize the known passage of As(OH)(3) through aqua-glyceroporines.

Cardiac magnetic resonance versus transthoracic echocardiography for the assessment of cardiac volumes and regional function after myocardial infarction: an intrasubject comparison using simultaneous intrasubject recordings.

BACKGROUND: Although echocardiography is commonly used to evaluate cardiac function after MI, CMR may provide more accurate functional assessment but has not been adequately compared with echo. The primary study objective was to compare metrics of left ventricular volumes and global and regional function determined by cardiac magnetic resonance (CMR) and echocardiography (echo) in patients (pts) with recent myocardial infarction (MI). METHODS: To compare CMR with echo, 47 consecutive patients (pts 70% male; mean age = 66 +/- 11 years) with MI >6 wks previously and scheduled for imaging evaluation were studied by both echo and CMR within 60 min of each other. Readers were blinded to pt information. Pearson's correlation coefficient, paired t-tests, and chi-square tests were used to compare CMR and echo measures. Further comparisons were made between pts and 30 normal controls for CMR and between pts and published normal ranges for echo. RESULTS: Measures of volume and function correlated moderately well between CMR and echo (r = 0.54 to 0.75, all p < 0.001), but large and systematic differences were noted in absolute measurements. Echo underestimated left ventricular (LV) volumes (by 69 ml for end-diastolic, 35 ml for end-systolic volume, both p < 0.001), stroke volume (by 34 ml, p < 0.001), and LV ejection fraction (LVEF) (by 4 percentage point, p = 0.02). CMR was much more sensitive to detection of segmental wall motion abnormalities (p < 0.001). CMR comparisons with normal controls confirmed an increase in LV volumes, a decrease in LVEF, and preservation of stroke volume after MI. CONCLUSION: This intra subject comparison after MI found large, systematic differences between CMR and echo measures of volumes, LVEF, and wall motion abnormality despite moderate inter-modality correlations, with echo underestimating each metric. CMR also provided superior detection and quantification of segmental function after MI. Serial studies of LV function in individual patients should use the same modality.

The kick with the kite: an analysis of kite surfing related off shore rescue missions in Cape Town, South Africa.

BACKGROUND: This study analyses kite surfing related off shore rescue missions in Cape Town, South Africa with the aim of providing more information on the frequency, pattern, and severity of kite surfing related injuries. METHODS: The observation period for this study started on October 1, 2003 and ended on May 1, 2004 and included 30 air rescue missions. Data and information were collected prospectively. RESULTS: The Air Mercy Service in Cape Town Province responded to 30 requests for help. Twenty five accidents were attributed to inability to detach the kite from the harness. Injuries occurred in five incidents and included fractures of the upper arm, ribs and ankle, and lacerations and contusions to the head and neck. Two patients suffered from hypothermia and one experienced severe exhaustion. All surfers were rescued successfully and there were no fatal accidents. DISCUSSION: The risk potential of this new sport is unclear. Dangerous situations can occur despite proper training and safety precautions due to unpredictable conditions and difficulties with equipment. Safety should be stressed. Surfers should sailing with a fellow kiter and should wear a life vest. More efforts must be taken to make this booming new water sport safer.

On the role of sterol in the formation of the amphotericin B channel.

Amphotericin B is an antimycotic agent that has been studied for a long time, both because of its pharmacological action and the interest in understanding how this ionic channel works. It has been proposed that the channel is formed by a barrel of monomers, and that the presence of sterol is needed for the formation of such a barrel. As a matter of fact this need of a sterol has been used as a guiding idea in attempts to design derivatives more efficient in the discrimination of the cholesterol containing membranes, as compared to the ergosterol containing ones, henceforth diminishing the unwanted side effects in its pharmacological use. In this work we show that unitary channels that appear in a cholesterol containing membrane also appear when this membrane is free of cholesterol. We prove this to be the case for two membranes, a biological one, asolectin, and a synthetic one, DMPC. We then advance the idea that the role of sterols in the formation of the amphotericin B channel is related to the effects they have on the structure of the membrane itself, rather than to a direct involvement in the channel formation. We further look into the effect that different cholesterol concentrations in the membrane produce on the single channel properties.

Access to psychiatric care; the results of the Pathways to Care study in Preston.

BACKGROUND: The aim of the present research was to study factors that might determine speed of access to psychiatric care, including the effect of the introduction of a community psychiatric service. METHODS: A Pathways to Care analysis was used to detail new referrals to mental health professionals (MHPs) during two one-month intervals one year apart, before and after the introduction of a community service (n = 279). Univariate analysis of possible factors that might affect access was undertaken, including socio-demographic factors, clinical factors and style of service. Significant associations were then investigated using stepwise logistic regression. RESULTS: The inception rate for treatment was similar to that reported for other services (0.10 per cent). After the establishment of community teams, there was an overall 22 per cent increase in the number of patients seen, with the greatest increase being for neurotic disorders and patients seen by non-medical staff. Of patient-based factors, younger age and suicidal ideation were associated with shorter pathways. Older age, married status, somatic symptoms, anxiety and depression were associated with slower pathways. Patients with suicidal ideation were seen within three days. The introduction of a community pathways team was associated with a lengthening of time to specialist care. CONCLUSIONS: Following a non-experimental change in service delivery, an increase in referrals for less severe mental illness was demonstrated. Continued comprehensive data collection of this type can be used by purchasers to monitor referral patterns and can provide a basis for determining priorities in service delivery.