Wireless electrical-molecular quantum signalling for cancer cell apoptosis.

Quantum biological tunnelling for electron transfer is involved in controlling essential functions for life such as cellular respiration and homoeostasis. Understanding and controlling the quantum effects in biology has the potential to modulate biological functions. Here we merge wireless nano-electrochemical tools with cancer cells for control over electron transfer to trigger cancer cell death. Gold bipolar nanoelectrodes functionalized with redox-active cytochrome c and a redox mediator zinc porphyrin are developed as electric-field-stimulating bio-actuators, termed bio-nanoantennae. We show that a remote electrical input regulates electron transport between these redox molecules, which results in quantum biological tunnelling for electron transfer to trigger apoptosis in patient-derived cancer cells in a selective manner. Transcriptomics data show that the electric-field-induced bio-nanoantenna targets the cancer cells in a unique manner, representing electrically induced control of molecular signalling. The work shows the potential of quantum-based medical diagnostics and treatments.

Photosensitisation of inkjet printed graphene with stable all-inorganic perovskite nanocrystals.

All-inorganic perovskite nanocrystals (NCs) with enhanced environmental stability are of particular interest for optoelectronic applications. Here we report on the formulation of CsPbX3 (X is Br or I) inks for inkjet deposition and utilise these NCs as photosensitive layers in graphene photodetectors, including those based on single layer graphene (SLG) as well as inkjet-printed graphene (iGr) devices. The performance of these photodetectors strongly depends on the device structure, geometry and the fabrication process. We achieve a high photoresponsivity, R > 106 A W-1 in the visible wavelength range and a spectral response controlled by the halide content of the perovskite NC ink. By utilising perovskite NCs, iGr and gold nanoparticle inks, we demonstrate a fully inkjet-printed photodetector with R ≈ 20 A W-1, which is the highest value reported to date for this type of device. The performance of the perovskite/graphene photodetectors is explained by transfer of photo-generated charge carriers from the perovskite NCs into graphene and charge transport through the iGr network. The perovskite ink developed here enabled realisation of stable and sensitive graphene-based photon detectors. Compatibility of inkjet deposition with conventional Si-technologies and with flexible substrates combined with high degree of design freedom provided by inkjet deposition offers opportunities for partially and fully printed optoelectronic devices for applications ranging from electronics to environmental sciences.

Graphene FETs with high and low mobilities have universal temperature-dependent properties.

We use phenomenological modelling and detailed experimental studies of charge carrier transport to investigate the dependence of the electrical resistivity,ρ, on gate voltage,Vg, for a series of monolayer graphene field effect transistors with mobilities,µ, ranging between 5000 and 250 000 cm2V-1s-1at low-temperature. Our measurements over a wide range of temperatures from 4 to 400 K can be fitted by the universal relationµ=4/eδnmaxfor all devices, whereρmaxis the resistivity maximum at the neutrality point andδnis an 'uncertainty' in the bipolar carrier density, given by the full width at half maximum of the resistivity peak expressed in terms of carrier density,n. This relation is consistent with thermal broadening of the carrier distribution and the presence of the disordered potential landscape consisting of so-called electron-hole puddles near the Dirac point. To demonstrate its utility, we combine this relation with temperature-dependent linearised Boltzmann transport calculations that include the effect of optical phonon scattering. This approach demonstrates the similarity in the temperature-dependent behaviour of carriers in different types of single layer graphene transistors with widely differing carrier mobilities. It can also account for the relative stability, over a wide temperature range, of the measured carrier mobility of each device.

Strengthening Management, Community Engagement, and Sustainability of the Subnational Response to Accelerate Malaria Elimination in Namibia.

Leadership and management skills are critical for health programs to deliver high-quality interventions in complex systems. In malaria-eliminating countries, national and subnational health teams are reorienting strategies to address focal transmission while preventing new cases and adapting to decentralization and declines in external financing. A capacity-strengthening program in two regions in Namibia helped malaria program implementers identify and address key operational, political, and financial challenges. The program focused on developing skills and techniques in problem-solving and teamwork, engaging decision-makers, and using financial evidence to prioritize domestic resources for malaria through participatory approaches. Results of the program included an observed 40% increase in malaria case reporting, 32% increase in reporting and tracing of imported malaria cases, 10% increase in malaria case management, integration of malaria activities into local operational plans, and an increase in subnational resources for malaria teams. To promote program sustainability beyond the implementation period, key program aspects were institutionalized into existing health system structures, program staff were trained in change leadership, and participants integrated the skills and approaches into their professional roles. A capacity -strengthening program with joint focus on leadership, management, and advocacy has potential for application to other health issues and geographies.

Effective management of district-level malaria control and elimination: implementing quality and participative process improvements.

Although it is widely recognized that strong program management is essential to achieving better health outcomes, this priority is not recognized in malaria programmatic practices. Increased management precision offers the opportunity to improve the effectiveness of malaria interventions, overcoming operational barriers to intervention coverage and accelerating the path to elimination. Here we propose a combined approach involving quality improvement, quality management, and participative process improvement, which we refer to as Combined Quality and Process Improvement (CQPI), to improve upon malaria program management. We draw on evidence from other areas of public health, as well as pilot implementation studies in Eswatini, Namibia and Zimbabwe to support the proposal. Summaries of the methodological approaches employed in the pilot studies, overview of activities and an outline of lessons learned from the implementation of CQPI are provided. Our findings suggest that a malaria management strategy that prioritizes quality and participative process improvements at the district-level can strengthen teamwork and communication while enabling the empowerment of subnational staff to solve service delivery challenges. Despite the promise of CQPI, however, policy makers and donors are not aware of its potential. Investments are therefore needed to allow CQPI to come to fruition.

Upper gastrointestinal tract involvement in Crohn's disease: A case report.

BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease that typically affects the distal part of the gastrointestinal tract (GI) such as the terminal ileum and colon. However, it can affect the upper GI tract, potentially resulting in complications such as strictures, but discussion of the management of such effects is limited in the surgical literature. CASE PRESENTATION: A 39 year old male was referred to our department with stricturing upper GI disease 20 years after CD diagnosis. He had a history of intermittent abdominal pain, nausea, frequent vomiting and weight loss. Imaging demonstrated a long stricture in the duodenum with proximal dilatation. There was no evidence of acute inflammatory Crohn's disease. A Roux-en-Y bypass was performed to successfully relieve the obstructive symptoms. DISCUSSION: Proximal obstructive gastrointestinal manifestations of CD are a rare entity and require a full diagnostic workup and treatment in a specialist centre. A variety of systemic treatments, endoscopic procedures and surgical techniques are addressed in this paper. CONCLUSION: Evidence for the optimal treatment of obstructive upper gastrointestinal CD is limited, but careful consideration of the extent of the disease, thorough preoperative planning and weighing up the benefits and risks can lead to a positive outcome for these patients.

Scaling up malaria elimination management and leadership: a pilot in three provinces in Zimbabwe, 2016-2018.

BACKGROUND: Focus for improved malaria programme performance is often placed on the technical challenges, while operational issues are neglected. Many of the operational challenges that inhibit malaria programme effectiveness can be addressed by improving communication and coordination, increasing accountability, maintaining motivation, providing adequate training and supervision, and removing bureaucratic silos. METHODS: A programme of work was piloted in Zimbabwe with one malaria eliminating province, Matabeleland South in 2016-2017, and scaled up to include two other provinces, Matabeleland North and Midlands, in 2017-2018. The intervention included participatory, organization development and quality improvement methods. RESULTS: Workshop participants in Matabeleland South reported an improvement in data management. In Matabeleland North, motivation among nurses improved as they gained confidence in case management from training, and overall staff morale improved. There was also an improvement in data quality and data sharing. In Midlands, the poorly performing district was motivated to improve, and both participating districts became more goal-oriented. They also became more focused on monitoring their data regularly. Participants from all provinces reported having gained skills in listening, communicating, facilitating discussions, and making presentations. Participation in the intervention changed the mindset of malaria programme staff, increasing ownership and accountability, and empowering them to identify and solve problems, make decisions, and act within their sphere of influence, elevating challenges when appropriate. CONCLUSIONS: This pilot demonstrates that a participatory, organization development and quality improvement approach has broad ranging effects, including improving local delivery of interventions, tailoring strategies to target specific populations, finding efficiencies in the system that could not be found using the traditional top-down approach, and improving motivation and communication between different cadres of health workers. Scale-up of this simple model can be achieved and benefits sustained over time if the process is imbedded into the programme with the training of health staff who can serve as management improvement coaches. Methods to improve operational performance that are scalable at the district level are urgently needed: this approach is a possible tactic that can significantly contribute to the achievement of global malaria eradication goals.

High-resolution anal manometry: Repeatability, validation, and comparison with conventional manometry.

BACKGROUND: Accurate measurement of anal sphincter function is potentially of value in defining treatment of common pelvic floor disorders. The aim of this study was to establish repeatability and validate high-resolution anorectal manometry (HRAM) by comparison to conventional manometry (CM). Arising from this work would be definitive normal range data. METHODS: Eighty healthy volunteers (40 female) underwent a test-retest repeatability study. A 16-channel water-perfused HRAM catheter was compared to an 8-channel conventional catheter using a station pull-through technique. KEY RESULTS: High-resolution anorectal manometry had similar precision to conventional manometry when measuring resting pressure (intraclass correlation coefficient [ICC] 0.73 vs 0.68, HRAM vs CM) and squeeze increment (ICC 0.90 vs 0.94, HRAM vs CM). HRAM measured resting pressures 10% lower than CM and squeeze pressure 27% higher than CM. CONCLUSIONS AND INFERENCES: High-resolution anorectal manometry is a valid technique with comparable precision to CM. HRAM measurements differ considerably to CM, and a new set of normal values must be used.

Effective program management: a cornerstone of malaria elimination.

Effective program management is essential for successful elimination of malaria. In this perspective article, evidence surrounding malaria program management is reviewed by management science and malaria experts through a literature search of published and unpublished gray documents and key informant interviews. Program management in a malaria elimination setting differs from that in a malaria control setting in a number of ways, although knowledge and understanding of these distinctions are lacking. Several core features of successful health program management are critical to achieve elimination, including effective leadership and supervision at all levels, sustained political and financial commitment, reliable supply and control of physical resources, effective management of data and information, appropriate incentives, and consistent accountability. Adding to the complexity, the requirements of an elimination program may conflict with those of a control regimen. Thus, an additional challenge is successfully managing program transitions along the continuum from control to elimination to prevention of reintroduction. This article identifies potential solutions to these challenges by exploring managerial approaches that are flexible, relevant, and sustainable in various cultural and health system contexts.

Epiploic appendagitis with acute appendicitis.

A 28-year-old woman presented to accident and emergency department with a 1-day history of right-sided abdominal pain. She was afebrile, and haemodynamically stable, and the initial diagnosis was acute appendicitis. A transvaginal ultrasound scan was performed and was suggestive of appendicitis. The patient failed to improve with conservative management, and a laparosocopic appendicectomy was performed the next day to remove an inflamed, non-perforated appendix. Pelvic laparoscopy was performed, which noted normal ovaries and uterus, as well as a hard, swollen, discoloured epiploic appendage of the sigmoid colon. A decision was made not to remove the inflamed epiploic appendage. Postoperatively the patient complained of persisting pain, which settled over 2 days with analgesia and antibiotics. This case is an extremely unusual case of epiploic appendagitis and acute appendicitis. It demonstrates the importance of pelvic laparoscopy in all females with presumed appendicitis, even in the presence of an initial pathology.

Transanal irrigation for bowel symptoms in patients with multiple sclerosis.

BACKGROUND: Constipation and fecal incontinence affect 68% of patients with multiple sclerosis, but management is empirical. Transanal irrigation has been used successfully in patients with neurogenic bowel dysfunction. OBJECTIVE: The aim of this study was to evaluate the effect of transanal irrigation on the bowel symptoms and general health status in these patients and the characteristics of those that had successful treatment and to obtain data for power calculations necessary for future randomized controlled studies. DESIGN: This was a prospective observational study in which pre- and posttreatment questionnaires (bowel symptoms and health status) were compared. Patients for whom treatment resulted in at least 50% improvement in bowel symptoms were considered responders. Baseline variables including anorectal physiology tests and rectal compliance were compared between responders and nonresponders. SETTINGS: This study was conducted at a specialist neurogastroenterology clinic, tertiary referral center. PATIENTS: Included were 30 patients who had multiple sclerosis and constipation, fecal incontinence, or both. INTERVENTION: Transanal irrigation was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the Wexner Constipation and Wexner Incontinence scores. The secondary outcomes was the SF-36 health survey. All scores were recorded before and after 6 weeks of treatment. RESULTS: At 6 weeks posttreatment, the Wexner Constipation score significantly improved (12 (8.75/16) pretreatment vs 8 (4/12.5) posttreatment, p = 0.001), as well as the Wexner Incontinence score (12 (4.75/16) pretreatment vs 4 (2/8) posttreatment, p < 0.001). The SF-36 score did not improve significantly (51.3 ± 7.8 pretreatment vs 50.4 ± 7.8 posttreatment, p = 0.051). Sixteen patients were responders and had higher baseline Wexner Incontinence scores (14 (11/20) responders vs 9 (4/15) nonresponders, p = 0.038) and SF-36 (53.9 ± 6.3 responders vs 47.9 ± 7.8 nonresponders, p = 0.027), as well as greater maximum tolerated volume to rectal balloon distension (310 (220/320) mL responders vs 168 (108/305) mL nonresponders, p = 0.017) and rectal compliance (15.2 (14.5/17.2) mL/mmHg responders vs 9.2 (7.2/15.3) mL/mmHg nonresponders, p = 0.019). LIMITATIONS: This study was limited by its small sample size and the lack of control group with alternative treatment. CONCLUSIONS: Transanal irrigation is effective to treat bowel symptoms in patients with multiple sclerosis. Responders (53%) had higher baseline incontinence symptoms and better perception of their health, as well as a more capacious and compliant rectum.

Heterotopic pancreas of the gallbladder associated with chronic cholecystitis.

CONTEXT: The presentation of heterotopic pancreas with cholecystolithiasis is exceedingly rare. Very few cases have been reported in the literature. The clinical significance so far is unclear. CASE REPORT: We report a case of a 20-year-old female, suffering with biliary colic. On clinical examination abdomen was unremarkable. Ultrasonographic examination shows suspicion of a single stone in the gallbladder. Her liver functions were slightly abnormal. MRCP did not show any abnormality in the gallbladder and the common bile duct was of normal caliber. She underwent a successful laparoscopic cholecystectomy and her symptoms resolved. Pathological examination of the gallbladder revealed an area of heterotopic pancreas. CONCLUSION: The preoperative diagnosis of heterotopic pancreas in the gallbladder is difficult. The significance of incidental finding of heterotopic pancreas in unclear and requires a systematic review of the subject.

The five minds of a manager.

Managers are told: Be global and be local. Collaborate and compete. Change, perpetually, and maintain order. Make the numbers while nurturing your people. To be effective, managers need to consider the juxtapositions in order to arrive at a deep integration of these seemingly contradictory concerns. That means they must focus not only on what they have to accomplish but also on how they have to think. When the authors, respectively the director of the Centre for Leadership Studies at the University of Exeter in the U.K. and the Cleghorn Professor of Management Studies at McGill University in Montreal, set out to develop a masters program for practicing managers, they saw that they could not rely on the usual MBA educational structure, which divides the management world into discrete business functions such as marketing and accounting. They needed an educational structure that would encourage synthesis rather than separation. Managing, they determined, involves five tasks, each with its own mind-set: managing the self (the reflective mind-set); managing organizations (the analytic mind-set); managing context (the worldly mind-set); managing relationships (the collaborative mind-set); and managing change (the action mind-set). The program is built on the exploration and integration of those five aspects of the managerial mind. The authors say it has proved powerful in the classroom and insightful in practice. Imagine the mind-sets as threads and the manager as weaver. Effective performance means weaving each mind-set over and under the others to create a fine, sturdy cloth.