Lapatinib-based therapy for women with advanced/metastatic HER2 positive breast cancer

Background: Lapatinib alone or in combination with other agents, mostly capecitabine is used for patients with advanced/metastatic HER2 positive breast cancer (HER2+BC) after progression on trastuzumab based therapy. Here we report our experience with lapatinib based therapy in this setting. Material and Methods: 67 consecutive patients received lapatinib based therapy. 58 (86.6%) received lapatinib + capecitabine (LC), 7 (10.4%) with other agents and 2 (3.0%) as single agent lapatinib. Data was collected from patients’ records retrospectively. Results: Objective response to lapatinib based therapy in 64 evaluable patients was 64.0% in all patients and 64.0% in patients who received LC. Median progression free survival and overall survival were 10 and 27 months in all patients and 10 and 17 months in patients who received LC, respectively. 16 (24.0%) patients had dose delay > 1 week and/or dose reduction. Conclusion: Lapatinib based therapy is an effective treatment for women with advanced/metastatic HER2+BC after prior exposure to trastuzumab. It yields meaningful response rates, progression free and overall survival. Some patients require dose adjustments. Key Words: lapatinib-based therapy, metastatic breast cancer, HER2 positive breast cancer, trastuzumab

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Effects of different irrigation regimes and nitrogenous fertilizer on yield and growth parameters of maize

A field experiment was carried out to find out the response on yield and yield contributing parameters of maize (cv. Bornali) to water stress and nitrogenous fertilizer. The experiment included two factors such as five irrigation regimes and four nitrogen levels. Texturally, the soil was silty loam. Yield and yield contributing characters were significantly affected due to the application of irrigation and nitrogen. The highest grain yield of 6.77 t/ha was obtained with IW/CPE ratio of 0.5 and 5.61 t/ha by the application of 70 kg N/ha. Interactions between IW/CPE ratio of 0.5 and 70 kg N/ha were the best combination for yield and yield contributing characters of maize

Analysis of return-to-zero-on-off-keying over absolute polar duty cycle division multiplexing in dispersive transmission medium

We propose and investigate a technique to reduce the spectral width as well as increase the tolerance to chromatic dispersion (CD) using improved return-to-zero (RZ) on-off-keying (OOK) over absolute polar duty cycle division multiplexing (AP-DCDM) technique. The proposed channel multiplexing and demultiplexing are performed electrically using only one modulator for n number of users, which is very economical. It is demonstrated that the spectral width occupied by 30 Gb/s RZ-OOK without AP-DCDM measured at 220 dB from the peak power is around 105 GHz whereas, this value can be reduced to around 64 GHz for 30 Gb/s RZ-OOK over AP-DCDM. This amount of saving in the spectral width is a significant achievement, which leads to better tolerance to CD. Its tolerance to CD is in the range of +/- 109 and +/- 155ps/nm, for the worst and the best users, respectively. These values are higher than that of 30 Gb/s conventional RZ-OOK, which is around +/- 86.5 ps/nm. At 120 Gb/s RZ-OOK over AP-DCDM ( the worst user) has pre-amplified receiver sensitivity and optical signal to noise ratio (OSNR) of 222.5 dBm and 28.57 dB, respectively

Decision circuit and bit error rate estimation for absolute polar duty cycle division multiplexing

A novel concepts of decision circuit and Bit-error-rate (BER) estimation method for Absolute Polar Duty Cycle Division Multiplexing (AP-DCDM) is proposed The concepts have significant differences to those used in conventional microwave communication receivers. This is due to the unique characteristics of the multilevel signal produced in AP-DCDM system. The BER estimation method is validated by simulation and compared against bit-to-bit comparison method

70-Gb/s amplitude-shift-keyed system with 10-GHz clock recovery circuit using duty cycle division multiplexing

The performance of ASK over DCDM for up to seven channels is reported. The aggregate bit rate of 70 Gb/s is achieved with only 160-GHz modulation bandwidth. The clock and data recovery are realized at 10-GHz clock rate, which is very economic and efficient. At 7 � 10 Gb/s, the worst receiver sensitivity of�10 dBm, OSNR of 41.5 dB and chromatic dispersion tolerance of ±17 ps/nm are achieved. Whereas, for the best channel, the receiver sensitivity,OSNR, and chromatic dispersion tolerance are �23.5dBm, 29dB, and ±36 ps/nm, respectively

LAPATINIB-BASED THERAPY FOR WOMEN WITH ADVANCED/ METASTATIC HER2 POSITIVE BREAST CANCER

Background: Lapatinib alone or in combination with other agents, mostly capecitabine is used for patients with advanced/metastatic HER2 positive breast cancer (HER2+BC) after progression on trastuzumab based therapy. Here we report our experience with lapatinib based therapy in this setting. Material and Methods: 67 consecutive patients received lapatinib based therapy. 58 (86.6%) received lapatinib + capecitabine (LC), 7 (10.4%) with other agents and 2 (3.0%) as single agent lapatinib. Data was collected from patients’ records retrospectively. Results: Objective response to lapatinib based therapy in 64 evaluable patients was 64.0% in all patients and 64.0% in patients who received LC. Median progression free survival and overall survival were 10 and 27 months in all patients and 10 and 17 months in patients who received LC, respectively. 16 (24.0%) patients had dose delay > 1 week and/or dose reduction. Conclusion: Lapatinib based therapy is an effective treatment for women with advanced/metastatic HER2+BC after prior exposure to trastuzumab. It yields meaningful response rates, progression free and overall survival. Some patients require dose adjustments. Key Words: lapatinib-based therapy, metastatic breast cancer, HER2 positive breast cancer, trastuzumab